JOURNAL CLUB (22-10-09)

topic autologus chondrocyte implantation

TOPIC AUTOLOGUS CHONDROCYTE IMPLANTATION

MODERATOR DR MBANSAL (MS DNB) DR P GUPTA (MS)

SPEAKER PRIYANK

GUPTA

THE ROLE OF AUTOLOGOUS CHONDROCYTE IMPLANTATION (ACI) IN THE TREATMENT OF ARTICULAR CARTILAGE DEFECTS IN THE KNEE JOINT

J A L Hart and J Paddle

PURPOSE To define the role of ACI in treatment of cartilage defects in the knee joint

METHOD 106 articular cartilage defects in 79 knees of 77 patients were treated by ACI as described by Brittberg et al 1994

-435 of the lesions involved the patella -352 the femoral condyles

-167 the trochlea and -46 the tibial condyles -20 of knees had more than one defect

Associated biomechanical procedures were carried out in 887

RESULTS ASSESSED ARTHROSCOPICALLY 9 MONTHS AFTER IMPLANTATION70 lesions in 58 knees and 56 patients 4 eligible patients were not assessed The average ICRS repair score (maximum 12) was as follows

-Tibial condyle 115 (4 defects) -Patella 113 (32 defects) -Femoral condyle 110(23 defects) -Trochlea 107 (11 defects)

Synovitis was markedly reduced in all knees with well healed defects Contraindications to ACI in this series were

-Non-contained defects

-Bi-polar lesions

-Patients greater than 45 years

-Uncorrected biomechanics

-Regional pain syndrome type 1

-Limited joint movement

-Defective subchondral bone plate

CONCLUSION ACI EFFECTIVELY REPAIRS ARTICULAR CARTILAGE DEFECTS IN THE KNEE JOINT PROVIDED THAT THE CONTRAINDICATIONS ARE RECOGNISED Unlike other series the results for the patella patellofemoral

joint have matched those for the femoral condyle This is attributed to the simultaneous biomechanical correction of the patellofemoral joint Stabilisation of the articular surface results in resolution of synovitis

AUTOLOGOUS CHONDROCYTE GRAFTS MULTICENTRIC TRIAL WITH 28 KNEE IMPLANTATIONS WITH MORE THAN TWO YEARS FOLLOW-UP

Journal of Bone and Joint Surgery - British Volume Vol 90-B Issue SUPP_II 252

Purpose of the study Spontaneous repair of lost deep chondral tissue is minimal in the knee joint A clinical trial of chondrocyte autografts as described by Brittberg and Peterson was undertaken by the Nantes University Hospital and the French Society of

Arthroscopy in 1999

Material and methods Twenty-eight patients mean age 28 years underwent surgery in eight centers Etiologies were

osteochondritis (n=14) isolated posttraumatic chondorpathy (n=7) chondropathy and full-thickness ACL tear (n=7)

All lesions involved the condyles and were deep (ICRS grds 3 and 4)

Mean surface area involved after debridement was 490 mm2 (range 150ndash1000 mm2)

Patients were followed three years after the autologous

grafting to assess functional outcome An MRI was obtained at 2ndash3 years Thirteen control arthroscopy procedures were performed

including eight with biopsy specimens for histology and

immunohisto-chemistry studies

RESULTS Twenty-six patients were reviewed at gt 2 yrs There were no general complications Three patients presented a partial avulsion of the graft treated by arthroscopy and

one underwent arthrolysis at six months FUNCTION improved in all patients except three and pain improved in all THE ICRS SCORE improved from 43 points (range 19ndash70) to 77 points (range 39ndash

84) Sixteen control MRIs were available and showed that

the graft was hypertrophic in eleven cases on level in four and insufficient in one Marginal integration was good in 11 cases and partial in five Subchondral integration was complete in ten cases and mediocre in six

THE ARTHROSCOPIC SCORE was nearly normal (score 8ndash11) in eight cases and

abnormal in five (score 4ndash7) THE HISTOLOGICAL CLASS according to Knutsen (hyaline richness) was

one in group 1 (gt60) three in group 2 (gt 40) four in group 3 (lt40) and one in group 4 (bony or fibrous tissue)

Function score (r=078 and MRI score (r=076) were correlated with arthroscopic sores There was no correlation with the histological results

DISCUSSION CLINICAL OUTCOME WAS IMPROVED IN MORE THAN 80 OF CASES SIMILAR TO RESULTS REPORTED FOR HISTOLOGICAL SERIES The arthroscopic and histological results were equivalent to those reported by Knutsen but inferior to those reported by Bentley or Peterson

ARTICULAR CARTILAGE

Chondrocytes (cartilage cells) embedded in a Highly specialised ECM

Gives elasticityProvides resistance to

tensilecompressive and shear forces

Acts as a smooth efficient surface for motion

HYALINE CARTILAGE STRUCTURE1048715THE ldquoSTUFFrdquo OF CARTILAGE

Functions of the Articular Cartilage ndash Distribute loadndash Absorb shock

CHONDRAL INJURIES

Deficient in type II collagen

Lower load bearing capacity

INEVITABLE lsquoSHORT TERMrsquo RECOVERY

Commonly these injuries heal by scar tissue formation

PREVALENCE AND INCIDENCE

993 consecutive arthroscopies ndash 66 articular cartilage pathology 11 full thickness localised lesions suitable for repair procedures

Aroen A Loken S Heir S et al Am J Sports Med 2004 32 211-15

31000 arthroscopic procedures ndash 63 articular cartilage lesions

Curl WW Krome J Gordon ES et al Arthroscopy 1997 13 456-60

1000 consecutive arthroscopies ndash 19 localised chondralosteochondral lesionsHjelle K et al Arthroscopy 2002 18 730-4

CARTILAGE INJURY OCCURS IN MANY FORMS

Trauma sports or work related

Chronic instability long term effects ACL and othermeniscal deficiency

Mal-aligned joint - deformityvarus Valgus

Osteochondritis Dissecans [OCD]

Genetic pre-disposition earlyarthritis

bull Most full-thickness defects are symptomaticndash Pain swelling locking catching grinding

bull Left untreatedmay progress to significant articular defects

ARTICULAR CARTILAGE DEFECTS A TREATMENT CHALLENGE

bullMay lead to debilitatingosteoarthritis

Arthroscopic Debridement

Arthroscopic lavage

Subchondral drilling

Microfracture MARROW STIMULATION TECHNIQUES Abrasion arthroplasty -to induce the growth of fibrocartilage into the chondral defect (This fibrocartilage does not withstand shock or shearing force as well as the original hyaline cartilage and may deteriorate over time)

AND WHAT IS IN OUR BASKET

AUTOLOGUS CHONDROCYTE IMPLANTATION

SO IT LED US TO SEARCH OF MORE PROMISING OPTION

JBJS [Am] 1987 Peterson et al Gothenburgndash first application of cell engineering in orthopaedics

NEJM 1994 Brittberg et al Swedenndash successfuly regenerated hyaline-like cartilage in isolated chondral defects

AUTOLOGOUS CHONDROCYTE IMPLANTATION (ACI) BACKGROUND

IDENTIFYING A CARTICELreg PATIENT

Patient FactorsYounger patients ndash lt age 45 - 50 (avg ~ 35 yo)

Significant impairment-Compromised daily livingactivities -Refractory to treatment

Obesity

Demanding Physical activities

Willing amp capable of rehabilitation program

IDENTIFYING A CARTICELreg PATIENThelliphellip

Joint FactorsSymptomatic cartilage defects -Moderate to large (gt 2cm2 d= 16) -On the distal femur (mfc lfc trochlea) -Average defect size gt 4 cm2

-Either chondral or osteochondral

Relatively healthy joint ndash -No arthritis

Co-morbidities(meniscal tear

instability or malalignment) must be corrected prior or concurrent to implantation

Pre-requisite for surgery

Not recommended for patients who have

Appropriate biomachenical alignment

Ligamentous stabilty

Range of motion

an unstable knee

patients sensitive to materials of bovine origins

allergic to the antibiotic gentamicin

in children

yet in any joint other than the knee

AUTOLOGOUS CHONDROCYTEIMPLANTATION (ACI)

StrengthsCan produce hyaline-like cartilageCan fill defects regardless of size with functional repair tissueModerate to large defects that have failed previous interventionRepair tissue which matures rather than deteriorates over timeExpected outcomeReturn to previous level of functioning

ldquoBiological Joint replacementrdquo

LimitationsMore invasiveExpenseLonger recovery

A ACI ndash Periosteum (cells under periosteum)

B ACI ndash Chondrogide (cells under membrane)

C MACI ndash Matrix Induced ACI (cells on membrane)

Chondrogide Membrane Porcine type IIII Inert Seal Resorbs in 3-4 months

ACI MACI

TECHNIQUES

Under inert collagen membrane (ACI)

On inert collagen membrane (MACI)

Harvest 200-300mg full thickness cartilage from trochlea (non load bearing)

Cells grown on monolayer with patients serum

No cells x 20-30

ACIMACI GENERIC METHOD

ACI METHOD

TREATMENT WITH CARTICEL

Uses your own cartilage cells (chondrocytes) to repair the articular cartilage damage in your knee When implanted into a cartilage injury your own cells can form new cartilage this new cartilage is very similar to your original cartilage The CARTICEL implantation procedure is called Autologous Chondrocyte Implantation or ACI It is a two-step process

Knee Cartilage Arthroscopy and BiopsyDuring an arthroscopic procedure surgeon assesses the extent of cartilage damage amp pt as a candidate for CARTICEL implantation

ldquoBiopsyrdquo of healthy tissue about the size of a pencil eraser ie about 200 -300 mg

From outer edge of sup Med or lat Femoral condyle or inner edge of lat Femoral condyle at the intercondylar notch

This sample is sent to product labs

Step 1 Biopsy

Biopsy can be stored for up to two years so you can schedule your surgery at your convenience

When you are ready your cells are cultured over three to five weeks they increase to approx 12 million cells in a vial containing 03 ndash 04 cc of medium Every step of the manufacturing process is monitored to ensure high quality and safety

CARTICEL MANUFACTURING AND DELIVERY

STEP 2 IMPLANTATION

Cartilage Injury CleanedDuring this second stage arthrotomy done to expose knee and any dead or damaged tissue from the injury removed with curette leaving only healthy tissue

Biomachenical allignment procedures if required should be done in conjunction with implantation

CARTICEL IMPLANTATION

PERIOSTEAL PATCH

surgeon takes a small piece of tissue from your shin bone and sews it securely over the injury

CARTICEL Implantation surgeon injects CARTICEL under the patch

When CARTICEL is surgically implanted into a cartilage injury it can grow and form new hyaline-like cartilage with properties similar to those of the original cartilage

Repairing the injury helps to reduce pain and improve movement and function

ACI STEPS summarised

MACI METHOD

Cultured chondrocytes seeded in bilayered typeIIII collagen membrane

Implanted using fibrin glue

Matrix remodelled in months replaced by extracellular matrix regenerate

The overall failure rate is at present quoted as being 10 The two most common complications include bullloosening of the transplant tissue bullformation of fibrous tissue at the repair site and adhesions with return of pain and locking Neither of these complications usually leaves the patient in a worse condition than hisher pre-transplantation state

Other adverse events include bullpost-op haematoma (big blood clot)bullhypertrophic synovitis (angry knee) and superficial wound infection

COMPLICATIONS

IMPROVEMENTS IN CLINICAL OUTCOME

ASSESMENT OF TECHNIQUE

FOLLOW UP RESULTS

ONE YEAR ASSESSMENT

Radiographs Alignment Bone quality

MRI Healing

cartilage Graft failure

Arthroscopy + probe Graft integrity Pressure biopsy

FOLLOW UP BIOPSY

FOLLOW UP MRI

Final appearance of theperiosteum sutured overfemoral condyle defect Thecartilage cells have beeninjected under the flap and thefinal suture placed to close thecover and provide a watertightseal

FOLLOW UP ARTHROSCOPIC

Arthroscopic appearance of thesame area 12 months afterCarticeltrade implantation Thedefect is no longer visible andthere is now hyaline cartilage(biopsy proven) filling theoriginal defect site

REHABILITATION GUIDELINES

Immobilization first 12-24 hours

(CPM) after 12-24 hours for about 4 weeks

Complete joint loading from about 5th week trochleapatellafrom about 8th week condyle Back to sports Low impact rarr within 6 monthsRepeated impact rarr from 8th monthHigh impact rarr from 10-12th month

ACI REHABILITATION

Weight bearingIt is recommended to keep you in non-weight bearing until the second week after surgery (ACI) You can increase the weight bearing gradually and you may be able to sustain your full weight bearing after 6 to 12 weeks from surgery

Range of motionRecovery on your ROM (Range of Motion) is gradually increased with a continuous passive motion (CPM) machine and may be completed to 140 degrees of ROM at 6 weeks to 12 weeks after surgery

ACI REHABILITATIONIndoor exerciseYou can strenghthen your muscles surrounding the knee joint with a four point exercise as well as isometric hamstring and squatting exercises from 4 weeks to 6 weeks after surgeryYou may start performing stationary bike activity without resistance and increase the resistance gradually

Outdoor exerciseAt 13 weeks after surgery you can start walking lightly and at 10 months after surgery you can perform jogging and then you may enjoy intensity exercise like playing tennis or volleyball from 18 months after surgery

Rehabilitation Goals at 12 weeks after ACIFull ROM (Range of Motion) Minimal edema level Minimal occasional pain Pain free tolerance to transitional phase exercise with adequate stability and motor control

COMPARISON WITH OTHER METHODS OF TREATMENTS

Autologous Chondrocyte Implantation Aims to increase the best condition for cartilage defectAdvantagesbullHyaline cartilage is formed bullPermanent reconstructed cartilage tissue bullMost valuable treatment

bullWith Fourth Generation ACI Use of cell ndash gel mixture (collagen hyaluronic acid and fibrin) has fast gelling properties (1 ndash 5 min) upon transplantation bullNo membrane or periosteal patch bullMinimal surgical exposure and reduced surgery time bullCorrects evenly irregular defect shapes bullApplicable to larger defects

COMPARISON WITH OTHER METHODS OF TREATMENTShelliphelliphellip

Abrasion arthroplastyAims to decrease the inflammation of the jointDisadvantagesbullRemoves many cartilage fragments from the jointbullSymptoms reoccur within one year

Drilling and MicrofractureAims to generate a healing responseDisadvantagesbullThe healing response in inadequate bullNo hyaline cartilage is formed but rather fibrocartilage bullHas a limited lifespan of approximately one year bullRapid deterioration after such procedures can be expected

COMPARISON WITH OTHER METHODS OF TREATMENTShelliphelliphellip

Perichondral ResurfacingDisadvantagesbullIsolated cartilage defects are often too large to be covered byh perichondrum bullLong term follow-up of such procedures indicate that the implants undergo endochondral ossification

Synthetic Materials (ie Carbon Fiber Mesh)Disadvantagesbull It often results in fibrous tissue formation bullNot adequate biomechanically bullOften the cause for synovitis in the joints

Osteocartiloginous GraftsAims to reconstruct jointsDisadvantagesbullUnless fresh cartilage is transplanted the cartilage is dead bullFresh grafts are not commonly used as they inevitably carry a risk of disease transmission bullCyropreserved grafts can survive for many years but ultimately deteriorate

Results of the Carticeltrade procedure have been encouraging although it is not always successful An analysis was done of the US and Swedish registry of 153 consecutive patients undergoing this procedure with follow-up from 1 week to 94 months The following results were obtainedbull Patients with clinical improvement 85bull Good or Excellent results 42 bull Good or Excellent results at 2 yearspersisting at 5 years post-op 97

Thus a total of 85 of patients showed some or complete improvement with theimplantation technique The Carticel procedure demonstrated good durability at 5-10 years out

CONCLUSIONS

CONCLUSIONS ACI Vs MACI No current evidence to justify aggressive treatment of

asymptomatic lesions with ACIMACI

Patients with full thickness symptomatic defects do poorly if left untreated

ACI and MACI lead to significant improvement in objective and patient reported clinical outcome scores for up to ten years(even among those with previous failed marrow stimulation techniques)

MACI has a superior rate of clinical improvement in comparison to ACI

Repair tissue may remodel and improve in quality with time

ACI and MACI comparable at 6 years

RECENT ADVANCESHYAFF 3D MATRIX

HYAFF biomaterialscontain high quantities ofderivatized HA

HA-richchondrocyte compatibleembryonic-like mileuconductive to regenerativehealing patterns

bull Non woven felt 2 mm thick fiber diameter 10 micronsbull Chondrocytes are isolated and passaged in culture on plasticdishes up to 3 weeksbull Cells are seeded for 2 weeks on HYAFF scaffold at a density of1 x 106 cm2 resulting in a total of 4 x 106 cm2 seeded cells pergraft

HYAFF-BASED SCAFFOLD

CHONDRONtrade

Uses a cell ndash gel mixture (includes collagen hyaluronic acid and fibrin) that has fast gelling properties (1 ndash 5 min) upon transplantation

This cell and gel mixture enable even cell distribution three-dimensionally moldable to fit irregular defect shape and applicable to a larger defectThus there is minimal surgical exposure and reduced surgery time

(three-dimensional reconstruction of a chondron from the growth plate of the murine long bone the model was generated from multiple sections imaged in an electron microscope plasma membranes are coloured green and internal organelles are visible within the top cell)

RECOVERY TO

HEALTHY ACTIVE LIFE

THANK YOU

• journal club (22-10-09)
• topic autologus chondrocyte implantation
• THE ROLE OF AUTOLOGOUS CHONDROCYTE IMPLANTATION (ACI) IN THE TR
• Slide 4
• AUTOLOGOUS CHONDROCYTE GRAFTS MULTICENTRIC TRIAL WITH 28 KNEE
• Slide 6
• Slide 7
• Articular Cartilage
• Hyaline Cartilage Structure 1048715The ldquostuffrdquo of cartilage
• Slide 11
• Cartilage Injury Occurs in Many Forms
• Articular Cartilage Defects a treatment challenge
• AND WHAT IS IN OUR BASKET
• SO IT LED US TO SEARCH OF MORE PROMISING OPTION
• Autologous Chondrocyte Implantation (ACI) BACKGROUND
• Identifying a Carticelreg Patient
• Identifying a Carticelreg Patienthelliphellip
• Pre-requisite for surgery
• Autologous Chondrocyte Implantation (ACI)
• Techniques
• ACIMACI Generic Method
• Slide 23
• Treatment with CARTICEL
• CARTICEL Manufacturing and Delivery
• Step 2 Implantation
• CARTICEL Implantation
• Periosteal Patch
• Slide 29
• Slide 30
• Aci steps summarised
• Slide 32
• Complications
• Slide 34
• Slide 35
• FOLLOW UP Biopsy
• FOLLOW UP MRI
• FOLLOW UP ARTHROSCOPIC
• Rehabilitation guidelines
• ACI Rehabilitation
• ACI Rehabilitation (2)
• COMPARISON WITH OTHER METHODS OF TREATMENTS
• COMPARISON WITH OTHER METHODS OF TREATMENTShelliphelliphellip
• COMPARISON WITH OTHER METHODS OF TREATMENTShelliphelliphellip (2)
• CONCLUSIONS
• Slide 46
• Recent advancesHYAFF 3D matrix
• HYAFF-based Scaffold
• CHONDRONtrade
• RECOVERY TO
• Slide 51

TOPIC AUTOLOGUS CHONDROCYTE IMPLANTATION

MODERATOR DR MBANSAL (MS DNB) DR P GUPTA (MS)

SPEAKER PRIYANK

GUPTA

THE ROLE OF AUTOLOGOUS CHONDROCYTE IMPLANTATION (ACI) IN THE TREATMENT OF ARTICULAR CARTILAGE DEFECTS IN THE KNEE JOINT

J A L Hart and J Paddle

PURPOSE To define the role of ACI in treatment of cartilage defects in the knee joint

METHOD 106 articular cartilage defects in 79 knees of 77 patients were treated by ACI as described by Brittberg et al 1994

-435 of the lesions involved the patella -352 the femoral condyles

-167 the trochlea and -46 the tibial condyles -20 of knees had more than one defect

Associated biomechanical procedures were carried out in 887

RESULTS ASSESSED ARTHROSCOPICALLY 9 MONTHS AFTER IMPLANTATION70 lesions in 58 knees and 56 patients 4 eligible patients were not assessed The average ICRS repair score (maximum 12) was as follows

-Tibial condyle 115 (4 defects) -Patella 113 (32 defects) -Femoral condyle 110(23 defects) -Trochlea 107 (11 defects)

Synovitis was markedly reduced in all knees with well healed defects Contraindications to ACI in this series were

-Non-contained defects

-Bi-polar lesions

-Patients greater than 45 years

-Uncorrected biomechanics

-Regional pain syndrome type 1

-Limited joint movement

-Defective subchondral bone plate

CONCLUSION ACI EFFECTIVELY REPAIRS ARTICULAR CARTILAGE DEFECTS IN THE KNEE JOINT PROVIDED THAT THE CONTRAINDICATIONS ARE RECOGNISED Unlike other series the results for the patella patellofemoral

joint have matched those for the femoral condyle This is attributed to the simultaneous biomechanical correction of the patellofemoral joint Stabilisation of the articular surface results in resolution of synovitis

AUTOLOGOUS CHONDROCYTE GRAFTS MULTICENTRIC TRIAL WITH 28 KNEE IMPLANTATIONS WITH MORE THAN TWO YEARS FOLLOW-UP

Journal of Bone and Joint Surgery - British Volume Vol 90-B Issue SUPP_II 252

Purpose of the study Spontaneous repair of lost deep chondral tissue is minimal in the knee joint A clinical trial of chondrocyte autografts as described by Brittberg and Peterson was undertaken by the Nantes University Hospital and the French Society of

Arthroscopy in 1999

Material and methods Twenty-eight patients mean age 28 years underwent surgery in eight centers Etiologies were

osteochondritis (n=14) isolated posttraumatic chondorpathy (n=7) chondropathy and full-thickness ACL tear (n=7)

All lesions involved the condyles and were deep (ICRS grds 3 and 4)

Mean surface area involved after debridement was 490 mm2 (range 150ndash1000 mm2)

Patients were followed three years after the autologous

grafting to assess functional outcome An MRI was obtained at 2ndash3 years Thirteen control arthroscopy procedures were performed

including eight with biopsy specimens for histology and

immunohisto-chemistry studies

RESULTS Twenty-six patients were reviewed at gt 2 yrs There were no general complications Three patients presented a partial avulsion of the graft treated by arthroscopy and

one underwent arthrolysis at six months FUNCTION improved in all patients except three and pain improved in all THE ICRS SCORE improved from 43 points (range 19ndash70) to 77 points (range 39ndash

84) Sixteen control MRIs were available and showed that

the graft was hypertrophic in eleven cases on level in four and insufficient in one Marginal integration was good in 11 cases and partial in five Subchondral integration was complete in ten cases and mediocre in six

THE ARTHROSCOPIC SCORE was nearly normal (score 8ndash11) in eight cases and

abnormal in five (score 4ndash7) THE HISTOLOGICAL CLASS according to Knutsen (hyaline richness) was

one in group 1 (gt60) three in group 2 (gt 40) four in group 3 (lt40) and one in group 4 (bony or fibrous tissue)

Function score (r=078 and MRI score (r=076) were correlated with arthroscopic sores There was no correlation with the histological results

DISCUSSION CLINICAL OUTCOME WAS IMPROVED IN MORE THAN 80 OF CASES SIMILAR TO RESULTS REPORTED FOR HISTOLOGICAL SERIES The arthroscopic and histological results were equivalent to those reported by Knutsen but inferior to those reported by Bentley or Peterson

ARTICULAR CARTILAGE

Chondrocytes (cartilage cells) embedded in a Highly specialised ECM

Gives elasticityProvides resistance to

tensilecompressive and shear forces

Acts as a smooth efficient surface for motion

HYALINE CARTILAGE STRUCTURE1048715THE ldquoSTUFFrdquo OF CARTILAGE

Functions of the Articular Cartilage ndash Distribute loadndash Absorb shock

CHONDRAL INJURIES

Deficient in type II collagen

Lower load bearing capacity

INEVITABLE lsquoSHORT TERMrsquo RECOVERY

Commonly these injuries heal by scar tissue formation

PREVALENCE AND INCIDENCE

993 consecutive arthroscopies ndash 66 articular cartilage pathology 11 full thickness localised lesions suitable for repair procedures

Aroen A Loken S Heir S et al Am J Sports Med 2004 32 211-15

31000 arthroscopic procedures ndash 63 articular cartilage lesions

Curl WW Krome J Gordon ES et al Arthroscopy 1997 13 456-60

1000 consecutive arthroscopies ndash 19 localised chondralosteochondral lesionsHjelle K et al Arthroscopy 2002 18 730-4

CARTILAGE INJURY OCCURS IN MANY FORMS

Trauma sports or work related

Chronic instability long term effects ACL and othermeniscal deficiency

Mal-aligned joint - deformityvarus Valgus

Osteochondritis Dissecans [OCD]

Genetic pre-disposition earlyarthritis

bull Most full-thickness defects are symptomaticndash Pain swelling locking catching grinding

bull Left untreatedmay progress to significant articular defects

ARTICULAR CARTILAGE DEFECTS A TREATMENT CHALLENGE

bullMay lead to debilitatingosteoarthritis

Arthroscopic Debridement

Arthroscopic lavage

Subchondral drilling

Microfracture MARROW STIMULATION TECHNIQUES Abrasion arthroplasty -to induce the growth of fibrocartilage into the chondral defect (This fibrocartilage does not withstand shock or shearing force as well as the original hyaline cartilage and may deteriorate over time)

AND WHAT IS IN OUR BASKET

AUTOLOGUS CHONDROCYTE IMPLANTATION

SO IT LED US TO SEARCH OF MORE PROMISING OPTION

JBJS [Am] 1987 Peterson et al Gothenburgndash first application of cell engineering in orthopaedics

NEJM 1994 Brittberg et al Swedenndash successfuly regenerated hyaline-like cartilage in isolated chondral defects

AUTOLOGOUS CHONDROCYTE IMPLANTATION (ACI) BACKGROUND

IDENTIFYING A CARTICELreg PATIENT

Patient FactorsYounger patients ndash lt age 45 - 50 (avg ~ 35 yo)

Significant impairment-Compromised daily livingactivities -Refractory to treatment

Obesity

Demanding Physical activities

Willing amp capable of rehabilitation program

IDENTIFYING A CARTICELreg PATIENThelliphellip

Joint FactorsSymptomatic cartilage defects -Moderate to large (gt 2cm2 d= 16) -On the distal femur (mfc lfc trochlea) -Average defect size gt 4 cm2

-Either chondral or osteochondral

Relatively healthy joint ndash -No arthritis

Co-morbidities(meniscal tear

instability or malalignment) must be corrected prior or concurrent to implantation

Pre-requisite for surgery

Not recommended for patients who have

Appropriate biomachenical alignment

Ligamentous stabilty

Range of motion

an unstable knee

patients sensitive to materials of bovine origins

allergic to the antibiotic gentamicin

in children

yet in any joint other than the knee

AUTOLOGOUS CHONDROCYTEIMPLANTATION (ACI)

StrengthsCan produce hyaline-like cartilageCan fill defects regardless of size with functional repair tissueModerate to large defects that have failed previous interventionRepair tissue which matures rather than deteriorates over timeExpected outcomeReturn to previous level of functioning

ldquoBiological Joint replacementrdquo

LimitationsMore invasiveExpenseLonger recovery

A ACI ndash Periosteum (cells under periosteum)

B ACI ndash Chondrogide (cells under membrane)

C MACI ndash Matrix Induced ACI (cells on membrane)

Chondrogide Membrane Porcine type IIII Inert Seal Resorbs in 3-4 months

ACI MACI

TECHNIQUES

Under inert collagen membrane (ACI)

On inert collagen membrane (MACI)

Harvest 200-300mg full thickness cartilage from trochlea (non load bearing)

Cells grown on monolayer with patients serum

No cells x 20-30

ACIMACI GENERIC METHOD

ACI METHOD

TREATMENT WITH CARTICEL

Uses your own cartilage cells (chondrocytes) to repair the articular cartilage damage in your knee When implanted into a cartilage injury your own cells can form new cartilage this new cartilage is very similar to your original cartilage The CARTICEL implantation procedure is called Autologous Chondrocyte Implantation or ACI It is a two-step process

Knee Cartilage Arthroscopy and BiopsyDuring an arthroscopic procedure surgeon assesses the extent of cartilage damage amp pt as a candidate for CARTICEL implantation

ldquoBiopsyrdquo of healthy tissue about the size of a pencil eraser ie about 200 -300 mg

From outer edge of sup Med or lat Femoral condyle or inner edge of lat Femoral condyle at the intercondylar notch

This sample is sent to product labs

Step 1 Biopsy

Biopsy can be stored for up to two years so you can schedule your surgery at your convenience

When you are ready your cells are cultured over three to five weeks they increase to approx 12 million cells in a vial containing 03 ndash 04 cc of medium Every step of the manufacturing process is monitored to ensure high quality and safety

CARTICEL MANUFACTURING AND DELIVERY

STEP 2 IMPLANTATION

Cartilage Injury CleanedDuring this second stage arthrotomy done to expose knee and any dead or damaged tissue from the injury removed with curette leaving only healthy tissue

Biomachenical allignment procedures if required should be done in conjunction with implantation

CARTICEL IMPLANTATION

PERIOSTEAL PATCH

surgeon takes a small piece of tissue from your shin bone and sews it securely over the injury

CARTICEL Implantation surgeon injects CARTICEL under the patch

When CARTICEL is surgically implanted into a cartilage injury it can grow and form new hyaline-like cartilage with properties similar to those of the original cartilage

Repairing the injury helps to reduce pain and improve movement and function

ACI STEPS summarised

MACI METHOD

Cultured chondrocytes seeded in bilayered typeIIII collagen membrane

Implanted using fibrin glue

Matrix remodelled in months replaced by extracellular matrix regenerate

The overall failure rate is at present quoted as being 10 The two most common complications include bullloosening of the transplant tissue bullformation of fibrous tissue at the repair site and adhesions with return of pain and locking Neither of these complications usually leaves the patient in a worse condition than hisher pre-transplantation state

Other adverse events include bullpost-op haematoma (big blood clot)bullhypertrophic synovitis (angry knee) and superficial wound infection

COMPLICATIONS

IMPROVEMENTS IN CLINICAL OUTCOME

ASSESMENT OF TECHNIQUE

FOLLOW UP RESULTS

ONE YEAR ASSESSMENT

Radiographs Alignment Bone quality

MRI Healing

cartilage Graft failure

Arthroscopy + probe Graft integrity Pressure biopsy

FOLLOW UP BIOPSY

FOLLOW UP MRI

Final appearance of theperiosteum sutured overfemoral condyle defect Thecartilage cells have beeninjected under the flap and thefinal suture placed to close thecover and provide a watertightseal

FOLLOW UP ARTHROSCOPIC

Arthroscopic appearance of thesame area 12 months afterCarticeltrade implantation Thedefect is no longer visible andthere is now hyaline cartilage(biopsy proven) filling theoriginal defect site

REHABILITATION GUIDELINES

Immobilization first 12-24 hours

(CPM) after 12-24 hours for about 4 weeks

Complete joint loading from about 5th week trochleapatellafrom about 8th week condyle Back to sports Low impact rarr within 6 monthsRepeated impact rarr from 8th monthHigh impact rarr from 10-12th month

ACI REHABILITATION

Weight bearingIt is recommended to keep you in non-weight bearing until the second week after surgery (ACI) You can increase the weight bearing gradually and you may be able to sustain your full weight bearing after 6 to 12 weeks from surgery

Range of motionRecovery on your ROM (Range of Motion) is gradually increased with a continuous passive motion (CPM) machine and may be completed to 140 degrees of ROM at 6 weeks to 12 weeks after surgery

ACI REHABILITATIONIndoor exerciseYou can strenghthen your muscles surrounding the knee joint with a four point exercise as well as isometric hamstring and squatting exercises from 4 weeks to 6 weeks after surgeryYou may start performing stationary bike activity without resistance and increase the resistance gradually

Outdoor exerciseAt 13 weeks after surgery you can start walking lightly and at 10 months after surgery you can perform jogging and then you may enjoy intensity exercise like playing tennis or volleyball from 18 months after surgery

Rehabilitation Goals at 12 weeks after ACIFull ROM (Range of Motion) Minimal edema level Minimal occasional pain Pain free tolerance to transitional phase exercise with adequate stability and motor control

COMPARISON WITH OTHER METHODS OF TREATMENTS

Autologous Chondrocyte Implantation Aims to increase the best condition for cartilage defectAdvantagesbullHyaline cartilage is formed bullPermanent reconstructed cartilage tissue bullMost valuable treatment

bullWith Fourth Generation ACI Use of cell ndash gel mixture (collagen hyaluronic acid and fibrin) has fast gelling properties (1 ndash 5 min) upon transplantation bullNo membrane or periosteal patch bullMinimal surgical exposure and reduced surgery time bullCorrects evenly irregular defect shapes bullApplicable to larger defects

COMPARISON WITH OTHER METHODS OF TREATMENTShelliphelliphellip

Abrasion arthroplastyAims to decrease the inflammation of the jointDisadvantagesbullRemoves many cartilage fragments from the jointbullSymptoms reoccur within one year

Drilling and MicrofractureAims to generate a healing responseDisadvantagesbullThe healing response in inadequate bullNo hyaline cartilage is formed but rather fibrocartilage bullHas a limited lifespan of approximately one year bullRapid deterioration after such procedures can be expected

COMPARISON WITH OTHER METHODS OF TREATMENTShelliphelliphellip

Perichondral ResurfacingDisadvantagesbullIsolated cartilage defects are often too large to be covered byh perichondrum bullLong term follow-up of such procedures indicate that the implants undergo endochondral ossification

Synthetic Materials (ie Carbon Fiber Mesh)Disadvantagesbull It often results in fibrous tissue formation bullNot adequate biomechanically bullOften the cause for synovitis in the joints

Osteocartiloginous GraftsAims to reconstruct jointsDisadvantagesbullUnless fresh cartilage is transplanted the cartilage is dead bullFresh grafts are not commonly used as they inevitably carry a risk of disease transmission bullCyropreserved grafts can survive for many years but ultimately deteriorate

Results of the Carticeltrade procedure have been encouraging although it is not always successful An analysis was done of the US and Swedish registry of 153 consecutive patients undergoing this procedure with follow-up from 1 week to 94 months The following results were obtainedbull Patients with clinical improvement 85bull Good or Excellent results 42 bull Good or Excellent results at 2 yearspersisting at 5 years post-op 97

Thus a total of 85 of patients showed some or complete improvement with theimplantation technique The Carticel procedure demonstrated good durability at 5-10 years out

CONCLUSIONS

CONCLUSIONS ACI Vs MACI No current evidence to justify aggressive treatment of

asymptomatic lesions with ACIMACI

Patients with full thickness symptomatic defects do poorly if left untreated

ACI and MACI lead to significant improvement in objective and patient reported clinical outcome scores for up to ten years(even among those with previous failed marrow stimulation techniques)

MACI has a superior rate of clinical improvement in comparison to ACI

Repair tissue may remodel and improve in quality with time

ACI and MACI comparable at 6 years

RECENT ADVANCESHYAFF 3D MATRIX

HYAFF biomaterialscontain high quantities ofderivatized HA

HA-richchondrocyte compatibleembryonic-like mileuconductive to regenerativehealing patterns

bull Non woven felt 2 mm thick fiber diameter 10 micronsbull Chondrocytes are isolated and passaged in culture on plasticdishes up to 3 weeksbull Cells are seeded for 2 weeks on HYAFF scaffold at a density of1 x 106 cm2 resulting in a total of 4 x 106 cm2 seeded cells pergraft

HYAFF-BASED SCAFFOLD

CHONDRONtrade

Uses a cell ndash gel mixture (includes collagen hyaluronic acid and fibrin) that has fast gelling properties (1 ndash 5 min) upon transplantation

This cell and gel mixture enable even cell distribution three-dimensionally moldable to fit irregular defect shape and applicable to a larger defectThus there is minimal surgical exposure and reduced surgery time

(three-dimensional reconstruction of a chondron from the growth plate of the murine long bone the model was generated from multiple sections imaged in an electron microscope plasma membranes are coloured green and internal organelles are visible within the top cell)

RECOVERY TO

HEALTHY ACTIVE LIFE

THANK YOU

• journal club (22-10-09)
• topic autologus chondrocyte implantation
• THE ROLE OF AUTOLOGOUS CHONDROCYTE IMPLANTATION (ACI) IN THE TR
• Slide 4
• AUTOLOGOUS CHONDROCYTE GRAFTS MULTICENTRIC TRIAL WITH 28 KNEE
• Slide 6
• Slide 7
• Articular Cartilage
• Hyaline Cartilage Structure 1048715The ldquostuffrdquo of cartilage
• Slide 11
• Cartilage Injury Occurs in Many Forms
• Articular Cartilage Defects a treatment challenge
• AND WHAT IS IN OUR BASKET
• SO IT LED US TO SEARCH OF MORE PROMISING OPTION
• Autologous Chondrocyte Implantation (ACI) BACKGROUND
• Identifying a Carticelreg Patient
• Identifying a Carticelreg Patienthelliphellip
• Pre-requisite for surgery
• Autologous Chondrocyte Implantation (ACI)
• Techniques
• ACIMACI Generic Method
• Slide 23
• Treatment with CARTICEL
• CARTICEL Manufacturing and Delivery
• Step 2 Implantation
• CARTICEL Implantation
• Periosteal Patch
• Slide 29
• Slide 30
• Aci steps summarised
• Slide 32
• Complications
• Slide 34
• Slide 35
• FOLLOW UP Biopsy
• FOLLOW UP MRI
• FOLLOW UP ARTHROSCOPIC
• Rehabilitation guidelines
• ACI Rehabilitation
• ACI Rehabilitation (2)
• COMPARISON WITH OTHER METHODS OF TREATMENTS
• COMPARISON WITH OTHER METHODS OF TREATMENTShelliphelliphellip
• COMPARISON WITH OTHER METHODS OF TREATMENTShelliphelliphellip (2)
• CONCLUSIONS
• Slide 46
• Recent advancesHYAFF 3D matrix
• HYAFF-based Scaffold
• CHONDRONtrade
• RECOVERY TO
• Slide 51

THE ROLE OF AUTOLOGOUS CHONDROCYTE IMPLANTATION (ACI) IN THE TREATMENT OF ARTICULAR CARTILAGE DEFECTS IN THE KNEE JOINT

J A L Hart and J Paddle

PURPOSE To define the role of ACI in treatment of cartilage defects in the knee joint

METHOD 106 articular cartilage defects in 79 knees of 77 patients were treated by ACI as described by Brittberg et al 1994

-435 of the lesions involved the patella -352 the femoral condyles

-167 the trochlea and -46 the tibial condyles -20 of knees had more than one defect

Associated biomechanical procedures were carried out in 887

RESULTS ASSESSED ARTHROSCOPICALLY 9 MONTHS AFTER IMPLANTATION70 lesions in 58 knees and 56 patients 4 eligible patients were not assessed The average ICRS repair score (maximum 12) was as follows

-Tibial condyle 115 (4 defects) -Patella 113 (32 defects) -Femoral condyle 110(23 defects) -Trochlea 107 (11 defects)

Synovitis was markedly reduced in all knees with well healed defects Contraindications to ACI in this series were

-Non-contained defects

-Bi-polar lesions

-Patients greater than 45 years

-Uncorrected biomechanics

-Regional pain syndrome type 1

-Limited joint movement

-Defective subchondral bone plate

CONCLUSION ACI EFFECTIVELY REPAIRS ARTICULAR CARTILAGE DEFECTS IN THE KNEE JOINT PROVIDED THAT THE CONTRAINDICATIONS ARE RECOGNISED Unlike other series the results for the patella patellofemoral

joint have matched those for the femoral condyle This is attributed to the simultaneous biomechanical correction of the patellofemoral joint Stabilisation of the articular surface results in resolution of synovitis

AUTOLOGOUS CHONDROCYTE GRAFTS MULTICENTRIC TRIAL WITH 28 KNEE IMPLANTATIONS WITH MORE THAN TWO YEARS FOLLOW-UP

Journal of Bone and Joint Surgery - British Volume Vol 90-B Issue SUPP_II 252

Purpose of the study Spontaneous repair of lost deep chondral tissue is minimal in the knee joint A clinical trial of chondrocyte autografts as described by Brittberg and Peterson was undertaken by the Nantes University Hospital and the French Society of

Arthroscopy in 1999

Material and methods Twenty-eight patients mean age 28 years underwent surgery in eight centers Etiologies were

osteochondritis (n=14) isolated posttraumatic chondorpathy (n=7) chondropathy and full-thickness ACL tear (n=7)

All lesions involved the condyles and were deep (ICRS grds 3 and 4)

Mean surface area involved after debridement was 490 mm2 (range 150ndash1000 mm2)

Patients were followed three years after the autologous

grafting to assess functional outcome An MRI was obtained at 2ndash3 years Thirteen control arthroscopy procedures were performed

including eight with biopsy specimens for histology and

immunohisto-chemistry studies

RESULTS Twenty-six patients were reviewed at gt 2 yrs There were no general complications Three patients presented a partial avulsion of the graft treated by arthroscopy and

one underwent arthrolysis at six months FUNCTION improved in all patients except three and pain improved in all THE ICRS SCORE improved from 43 points (range 19ndash70) to 77 points (range 39ndash

84) Sixteen control MRIs were available and showed that

the graft was hypertrophic in eleven cases on level in four and insufficient in one Marginal integration was good in 11 cases and partial in five Subchondral integration was complete in ten cases and mediocre in six

THE ARTHROSCOPIC SCORE was nearly normal (score 8ndash11) in eight cases and

abnormal in five (score 4ndash7) THE HISTOLOGICAL CLASS according to Knutsen (hyaline richness) was

one in group 1 (gt60) three in group 2 (gt 40) four in group 3 (lt40) and one in group 4 (bony or fibrous tissue)

Function score (r=078 and MRI score (r=076) were correlated with arthroscopic sores There was no correlation with the histological results

DISCUSSION CLINICAL OUTCOME WAS IMPROVED IN MORE THAN 80 OF CASES SIMILAR TO RESULTS REPORTED FOR HISTOLOGICAL SERIES The arthroscopic and histological results were equivalent to those reported by Knutsen but inferior to those reported by Bentley or Peterson

ARTICULAR CARTILAGE

Chondrocytes (cartilage cells) embedded in a Highly specialised ECM

Gives elasticityProvides resistance to

tensilecompressive and shear forces

Acts as a smooth efficient surface for motion

HYALINE CARTILAGE STRUCTURE1048715THE ldquoSTUFFrdquo OF CARTILAGE

Functions of the Articular Cartilage ndash Distribute loadndash Absorb shock

CHONDRAL INJURIES

Deficient in type II collagen

Lower load bearing capacity

INEVITABLE lsquoSHORT TERMrsquo RECOVERY

Commonly these injuries heal by scar tissue formation

PREVALENCE AND INCIDENCE

993 consecutive arthroscopies ndash 66 articular cartilage pathology 11 full thickness localised lesions suitable for repair procedures

Aroen A Loken S Heir S et al Am J Sports Med 2004 32 211-15

31000 arthroscopic procedures ndash 63 articular cartilage lesions

Curl WW Krome J Gordon ES et al Arthroscopy 1997 13 456-60

1000 consecutive arthroscopies ndash 19 localised chondralosteochondral lesionsHjelle K et al Arthroscopy 2002 18 730-4

CARTILAGE INJURY OCCURS IN MANY FORMS

Trauma sports or work related

Chronic instability long term effects ACL and othermeniscal deficiency

Mal-aligned joint - deformityvarus Valgus

Osteochondritis Dissecans [OCD]

Genetic pre-disposition earlyarthritis

bull Most full-thickness defects are symptomaticndash Pain swelling locking catching grinding

bull Left untreatedmay progress to significant articular defects

ARTICULAR CARTILAGE DEFECTS A TREATMENT CHALLENGE

bullMay lead to debilitatingosteoarthritis

Arthroscopic Debridement

Arthroscopic lavage

Subchondral drilling

Microfracture MARROW STIMULATION TECHNIQUES Abrasion arthroplasty -to induce the growth of fibrocartilage into the chondral defect (This fibrocartilage does not withstand shock or shearing force as well as the original hyaline cartilage and may deteriorate over time)

AND WHAT IS IN OUR BASKET

AUTOLOGUS CHONDROCYTE IMPLANTATION

SO IT LED US TO SEARCH OF MORE PROMISING OPTION

JBJS [Am] 1987 Peterson et al Gothenburgndash first application of cell engineering in orthopaedics

NEJM 1994 Brittberg et al Swedenndash successfuly regenerated hyaline-like cartilage in isolated chondral defects

AUTOLOGOUS CHONDROCYTE IMPLANTATION (ACI) BACKGROUND

IDENTIFYING A CARTICELreg PATIENT

Patient FactorsYounger patients ndash lt age 45 - 50 (avg ~ 35 yo)

Significant impairment-Compromised daily livingactivities -Refractory to treatment

Obesity

Demanding Physical activities

Willing amp capable of rehabilitation program

IDENTIFYING A CARTICELreg PATIENThelliphellip

Joint FactorsSymptomatic cartilage defects -Moderate to large (gt 2cm2 d= 16) -On the distal femur (mfc lfc trochlea) -Average defect size gt 4 cm2

-Either chondral or osteochondral

Relatively healthy joint ndash -No arthritis

Co-morbidities(meniscal tear

instability or malalignment) must be corrected prior or concurrent to implantation

Pre-requisite for surgery

Not recommended for patients who have

Appropriate biomachenical alignment

Ligamentous stabilty

Range of motion

an unstable knee

patients sensitive to materials of bovine origins

allergic to the antibiotic gentamicin

in children

yet in any joint other than the knee

AUTOLOGOUS CHONDROCYTEIMPLANTATION (ACI)

StrengthsCan produce hyaline-like cartilageCan fill defects regardless of size with functional repair tissueModerate to large defects that have failed previous interventionRepair tissue which matures rather than deteriorates over timeExpected outcomeReturn to previous level of functioning

ldquoBiological Joint replacementrdquo

LimitationsMore invasiveExpenseLonger recovery

A ACI ndash Periosteum (cells under periosteum)

B ACI ndash Chondrogide (cells under membrane)

C MACI ndash Matrix Induced ACI (cells on membrane)

Chondrogide Membrane Porcine type IIII Inert Seal Resorbs in 3-4 months

ACI MACI

TECHNIQUES

Under inert collagen membrane (ACI)

On inert collagen membrane (MACI)

Harvest 200-300mg full thickness cartilage from trochlea (non load bearing)

Cells grown on monolayer with patients serum

No cells x 20-30

ACIMACI GENERIC METHOD

ACI METHOD

TREATMENT WITH CARTICEL

Uses your own cartilage cells (chondrocytes) to repair the articular cartilage damage in your knee When implanted into a cartilage injury your own cells can form new cartilage this new cartilage is very similar to your original cartilage The CARTICEL implantation procedure is called Autologous Chondrocyte Implantation or ACI It is a two-step process

Knee Cartilage Arthroscopy and BiopsyDuring an arthroscopic procedure surgeon assesses the extent of cartilage damage amp pt as a candidate for CARTICEL implantation

ldquoBiopsyrdquo of healthy tissue about the size of a pencil eraser ie about 200 -300 mg

From outer edge of sup Med or lat Femoral condyle or inner edge of lat Femoral condyle at the intercondylar notch

This sample is sent to product labs

Step 1 Biopsy

Biopsy can be stored for up to two years so you can schedule your surgery at your convenience

When you are ready your cells are cultured over three to five weeks they increase to approx 12 million cells in a vial containing 03 ndash 04 cc of medium Every step of the manufacturing process is monitored to ensure high quality and safety

CARTICEL MANUFACTURING AND DELIVERY

STEP 2 IMPLANTATION

Cartilage Injury CleanedDuring this second stage arthrotomy done to expose knee and any dead or damaged tissue from the injury removed with curette leaving only healthy tissue

Biomachenical allignment procedures if required should be done in conjunction with implantation

CARTICEL IMPLANTATION

PERIOSTEAL PATCH

surgeon takes a small piece of tissue from your shin bone and sews it securely over the injury

CARTICEL Implantation surgeon injects CARTICEL under the patch

When CARTICEL is surgically implanted into a cartilage injury it can grow and form new hyaline-like cartilage with properties similar to those of the original cartilage

Repairing the injury helps to reduce pain and improve movement and function

ACI STEPS summarised

MACI METHOD

Cultured chondrocytes seeded in bilayered typeIIII collagen membrane

Implanted using fibrin glue

Matrix remodelled in months replaced by extracellular matrix regenerate

The overall failure rate is at present quoted as being 10 The two most common complications include bullloosening of the transplant tissue bullformation of fibrous tissue at the repair site and adhesions with return of pain and locking Neither of these complications usually leaves the patient in a worse condition than hisher pre-transplantation state

Other adverse events include bullpost-op haematoma (big blood clot)bullhypertrophic synovitis (angry knee) and superficial wound infection

COMPLICATIONS

IMPROVEMENTS IN CLINICAL OUTCOME

ASSESMENT OF TECHNIQUE

FOLLOW UP RESULTS

ONE YEAR ASSESSMENT

Radiographs Alignment Bone quality

MRI Healing

cartilage Graft failure

Arthroscopy + probe Graft integrity Pressure biopsy

FOLLOW UP BIOPSY

FOLLOW UP MRI

Final appearance of theperiosteum sutured overfemoral condyle defect Thecartilage cells have beeninjected under the flap and thefinal suture placed to close thecover and provide a watertightseal

FOLLOW UP ARTHROSCOPIC

Arthroscopic appearance of thesame area 12 months afterCarticeltrade implantation Thedefect is no longer visible andthere is now hyaline cartilage(biopsy proven) filling theoriginal defect site

REHABILITATION GUIDELINES

Immobilization first 12-24 hours

(CPM) after 12-24 hours for about 4 weeks

Complete joint loading from about 5th week trochleapatellafrom about 8th week condyle Back to sports Low impact rarr within 6 monthsRepeated impact rarr from 8th monthHigh impact rarr from 10-12th month

ACI REHABILITATION

Weight bearingIt is recommended to keep you in non-weight bearing until the second week after surgery (ACI) You can increase the weight bearing gradually and you may be able to sustain your full weight bearing after 6 to 12 weeks from surgery

Range of motionRecovery on your ROM (Range of Motion) is gradually increased with a continuous passive motion (CPM) machine and may be completed to 140 degrees of ROM at 6 weeks to 12 weeks after surgery

ACI REHABILITATIONIndoor exerciseYou can strenghthen your muscles surrounding the knee joint with a four point exercise as well as isometric hamstring and squatting exercises from 4 weeks to 6 weeks after surgeryYou may start performing stationary bike activity without resistance and increase the resistance gradually

Outdoor exerciseAt 13 weeks after surgery you can start walking lightly and at 10 months after surgery you can perform jogging and then you may enjoy intensity exercise like playing tennis or volleyball from 18 months after surgery

Rehabilitation Goals at 12 weeks after ACIFull ROM (Range of Motion) Minimal edema level Minimal occasional pain Pain free tolerance to transitional phase exercise with adequate stability and motor control

COMPARISON WITH OTHER METHODS OF TREATMENTS

Autologous Chondrocyte Implantation Aims to increase the best condition for cartilage defectAdvantagesbullHyaline cartilage is formed bullPermanent reconstructed cartilage tissue bullMost valuable treatment

bullWith Fourth Generation ACI Use of cell ndash gel mixture (collagen hyaluronic acid and fibrin) has fast gelling properties (1 ndash 5 min) upon transplantation bullNo membrane or periosteal patch bullMinimal surgical exposure and reduced surgery time bullCorrects evenly irregular defect shapes bullApplicable to larger defects

COMPARISON WITH OTHER METHODS OF TREATMENTShelliphelliphellip

Abrasion arthroplastyAims to decrease the inflammation of the jointDisadvantagesbullRemoves many cartilage fragments from the jointbullSymptoms reoccur within one year

Drilling and MicrofractureAims to generate a healing responseDisadvantagesbullThe healing response in inadequate bullNo hyaline cartilage is formed but rather fibrocartilage bullHas a limited lifespan of approximately one year bullRapid deterioration after such procedures can be expected

COMPARISON WITH OTHER METHODS OF TREATMENTShelliphelliphellip

Perichondral ResurfacingDisadvantagesbullIsolated cartilage defects are often too large to be covered byh perichondrum bullLong term follow-up of such procedures indicate that the implants undergo endochondral ossification

Synthetic Materials (ie Carbon Fiber Mesh)Disadvantagesbull It often results in fibrous tissue formation bullNot adequate biomechanically bullOften the cause for synovitis in the joints

Osteocartiloginous GraftsAims to reconstruct jointsDisadvantagesbullUnless fresh cartilage is transplanted the cartilage is dead bullFresh grafts are not commonly used as they inevitably carry a risk of disease transmission bullCyropreserved grafts can survive for many years but ultimately deteriorate

Results of the Carticeltrade procedure have been encouraging although it is not always successful An analysis was done of the US and Swedish registry of 153 consecutive patients undergoing this procedure with follow-up from 1 week to 94 months The following results were obtainedbull Patients with clinical improvement 85bull Good or Excellent results 42 bull Good or Excellent results at 2 yearspersisting at 5 years post-op 97

Thus a total of 85 of patients showed some or complete improvement with theimplantation technique The Carticel procedure demonstrated good durability at 5-10 years out

CONCLUSIONS

CONCLUSIONS ACI Vs MACI No current evidence to justify aggressive treatment of

asymptomatic lesions with ACIMACI

Patients with full thickness symptomatic defects do poorly if left untreated

ACI and MACI lead to significant improvement in objective and patient reported clinical outcome scores for up to ten years(even among those with previous failed marrow stimulation techniques)

MACI has a superior rate of clinical improvement in comparison to ACI

Repair tissue may remodel and improve in quality with time

ACI and MACI comparable at 6 years

RECENT ADVANCESHYAFF 3D MATRIX

HYAFF biomaterialscontain high quantities ofderivatized HA

HA-richchondrocyte compatibleembryonic-like mileuconductive to regenerativehealing patterns

bull Non woven felt 2 mm thick fiber diameter 10 micronsbull Chondrocytes are isolated and passaged in culture on plasticdishes up to 3 weeksbull Cells are seeded for 2 weeks on HYAFF scaffold at a density of1 x 106 cm2 resulting in a total of 4 x 106 cm2 seeded cells pergraft

HYAFF-BASED SCAFFOLD

CHONDRONtrade

Uses a cell ndash gel mixture (includes collagen hyaluronic acid and fibrin) that has fast gelling properties (1 ndash 5 min) upon transplantation

This cell and gel mixture enable even cell distribution three-dimensionally moldable to fit irregular defect shape and applicable to a larger defectThus there is minimal surgical exposure and reduced surgery time

(three-dimensional reconstruction of a chondron from the growth plate of the murine long bone the model was generated from multiple sections imaged in an electron microscope plasma membranes are coloured green and internal organelles are visible within the top cell)

RECOVERY TO

HEALTHY ACTIVE LIFE

THANK YOU

• journal club (22-10-09)
• topic autologus chondrocyte implantation
• THE ROLE OF AUTOLOGOUS CHONDROCYTE IMPLANTATION (ACI) IN THE TR
• Slide 4
• AUTOLOGOUS CHONDROCYTE GRAFTS MULTICENTRIC TRIAL WITH 28 KNEE
• Slide 6
• Slide 7
• Articular Cartilage
• Hyaline Cartilage Structure 1048715The ldquostuffrdquo of cartilage
• Slide 11
• Cartilage Injury Occurs in Many Forms
• Articular Cartilage Defects a treatment challenge
• AND WHAT IS IN OUR BASKET
• SO IT LED US TO SEARCH OF MORE PROMISING OPTION
• Autologous Chondrocyte Implantation (ACI) BACKGROUND
• Identifying a Carticelreg Patient
• Identifying a Carticelreg Patienthelliphellip
• Pre-requisite for surgery
• Autologous Chondrocyte Implantation (ACI)
• Techniques
• ACIMACI Generic Method
• Slide 23
• Treatment with CARTICEL
• CARTICEL Manufacturing and Delivery
• Step 2 Implantation
• CARTICEL Implantation
• Periosteal Patch
• Slide 29
• Slide 30
• Aci steps summarised
• Slide 32
• Complications
• Slide 34
• Slide 35
• FOLLOW UP Biopsy
• FOLLOW UP MRI
• FOLLOW UP ARTHROSCOPIC
• Rehabilitation guidelines
• ACI Rehabilitation
• ACI Rehabilitation (2)
• COMPARISON WITH OTHER METHODS OF TREATMENTS
• COMPARISON WITH OTHER METHODS OF TREATMENTShelliphelliphellip
• COMPARISON WITH OTHER METHODS OF TREATMENTShelliphelliphellip (2)
• CONCLUSIONS
• Slide 46
• Recent advancesHYAFF 3D matrix
• HYAFF-based Scaffold
• CHONDRONtrade
• RECOVERY TO
• Slide 51

RESULTS ASSESSED ARTHROSCOPICALLY 9 MONTHS AFTER IMPLANTATION70 lesions in 58 knees and 56 patients 4 eligible patients were not assessed The average ICRS repair score (maximum 12) was as follows

-Tibial condyle 115 (4 defects) -Patella 113 (32 defects) -Femoral condyle 110(23 defects) -Trochlea 107 (11 defects)

Synovitis was markedly reduced in all knees with well healed defects Contraindications to ACI in this series were

-Non-contained defects

-Bi-polar lesions

-Patients greater than 45 years

-Uncorrected biomechanics

-Regional pain syndrome type 1

-Limited joint movement

-Defective subchondral bone plate

CONCLUSION ACI EFFECTIVELY REPAIRS ARTICULAR CARTILAGE DEFECTS IN THE KNEE JOINT PROVIDED THAT THE CONTRAINDICATIONS ARE RECOGNISED Unlike other series the results for the patella patellofemoral

joint have matched those for the femoral condyle This is attributed to the simultaneous biomechanical correction of the patellofemoral joint Stabilisation of the articular surface results in resolution of synovitis

AUTOLOGOUS CHONDROCYTE GRAFTS MULTICENTRIC TRIAL WITH 28 KNEE IMPLANTATIONS WITH MORE THAN TWO YEARS FOLLOW-UP

Journal of Bone and Joint Surgery - British Volume Vol 90-B Issue SUPP_II 252

Purpose of the study Spontaneous repair of lost deep chondral tissue is minimal in the knee joint A clinical trial of chondrocyte autografts as described by Brittberg and Peterson was undertaken by the Nantes University Hospital and the French Society of

Arthroscopy in 1999

Material and methods Twenty-eight patients mean age 28 years underwent surgery in eight centers Etiologies were

osteochondritis (n=14) isolated posttraumatic chondorpathy (n=7) chondropathy and full-thickness ACL tear (n=7)

All lesions involved the condyles and were deep (ICRS grds 3 and 4)

Mean surface area involved after debridement was 490 mm2 (range 150ndash1000 mm2)

Patients were followed three years after the autologous

grafting to assess functional outcome An MRI was obtained at 2ndash3 years Thirteen control arthroscopy procedures were performed

including eight with biopsy specimens for histology and

immunohisto-chemistry studies

RESULTS Twenty-six patients were reviewed at gt 2 yrs There were no general complications Three patients presented a partial avulsion of the graft treated by arthroscopy and

one underwent arthrolysis at six months FUNCTION improved in all patients except three and pain improved in all THE ICRS SCORE improved from 43 points (range 19ndash70) to 77 points (range 39ndash

84) Sixteen control MRIs were available and showed that

the graft was hypertrophic in eleven cases on level in four and insufficient in one Marginal integration was good in 11 cases and partial in five Subchondral integration was complete in ten cases and mediocre in six

THE ARTHROSCOPIC SCORE was nearly normal (score 8ndash11) in eight cases and

abnormal in five (score 4ndash7) THE HISTOLOGICAL CLASS according to Knutsen (hyaline richness) was

one in group 1 (gt60) three in group 2 (gt 40) four in group 3 (lt40) and one in group 4 (bony or fibrous tissue)

Function score (r=078 and MRI score (r=076) were correlated with arthroscopic sores There was no correlation with the histological results

DISCUSSION CLINICAL OUTCOME WAS IMPROVED IN MORE THAN 80 OF CASES SIMILAR TO RESULTS REPORTED FOR HISTOLOGICAL SERIES The arthroscopic and histological results were equivalent to those reported by Knutsen but inferior to those reported by Bentley or Peterson

ARTICULAR CARTILAGE

Chondrocytes (cartilage cells) embedded in a Highly specialised ECM

Gives elasticityProvides resistance to

tensilecompressive and shear forces

Acts as a smooth efficient surface for motion

HYALINE CARTILAGE STRUCTURE1048715THE ldquoSTUFFrdquo OF CARTILAGE

Functions of the Articular Cartilage ndash Distribute loadndash Absorb shock

CHONDRAL INJURIES

Deficient in type II collagen

Lower load bearing capacity

INEVITABLE lsquoSHORT TERMrsquo RECOVERY

Commonly these injuries heal by scar tissue formation

PREVALENCE AND INCIDENCE

993 consecutive arthroscopies ndash 66 articular cartilage pathology 11 full thickness localised lesions suitable for repair procedures

Aroen A Loken S Heir S et al Am J Sports Med 2004 32 211-15

31000 arthroscopic procedures ndash 63 articular cartilage lesions

Curl WW Krome J Gordon ES et al Arthroscopy 1997 13 456-60

1000 consecutive arthroscopies ndash 19 localised chondralosteochondral lesionsHjelle K et al Arthroscopy 2002 18 730-4

CARTILAGE INJURY OCCURS IN MANY FORMS

Trauma sports or work related

Chronic instability long term effects ACL and othermeniscal deficiency

Mal-aligned joint - deformityvarus Valgus

Osteochondritis Dissecans [OCD]

Genetic pre-disposition earlyarthritis

bull Most full-thickness defects are symptomaticndash Pain swelling locking catching grinding

bull Left untreatedmay progress to significant articular defects

ARTICULAR CARTILAGE DEFECTS A TREATMENT CHALLENGE

bullMay lead to debilitatingosteoarthritis

Arthroscopic Debridement

Arthroscopic lavage

Subchondral drilling

Microfracture MARROW STIMULATION TECHNIQUES Abrasion arthroplasty -to induce the growth of fibrocartilage into the chondral defect (This fibrocartilage does not withstand shock or shearing force as well as the original hyaline cartilage and may deteriorate over time)

AND WHAT IS IN OUR BASKET

AUTOLOGUS CHONDROCYTE IMPLANTATION

SO IT LED US TO SEARCH OF MORE PROMISING OPTION

JBJS [Am] 1987 Peterson et al Gothenburgndash first application of cell engineering in orthopaedics

NEJM 1994 Brittberg et al Swedenndash successfuly regenerated hyaline-like cartilage in isolated chondral defects

AUTOLOGOUS CHONDROCYTE IMPLANTATION (ACI) BACKGROUND

IDENTIFYING A CARTICELreg PATIENT

Patient FactorsYounger patients ndash lt age 45 - 50 (avg ~ 35 yo)

Significant impairment-Compromised daily livingactivities -Refractory to treatment

Obesity

Demanding Physical activities

Willing amp capable of rehabilitation program

IDENTIFYING A CARTICELreg PATIENThelliphellip

Joint FactorsSymptomatic cartilage defects -Moderate to large (gt 2cm2 d= 16) -On the distal femur (mfc lfc trochlea) -Average defect size gt 4 cm2

-Either chondral or osteochondral

Relatively healthy joint ndash -No arthritis

Co-morbidities(meniscal tear

instability or malalignment) must be corrected prior or concurrent to implantation

Pre-requisite for surgery

Not recommended for patients who have

Appropriate biomachenical alignment

Ligamentous stabilty

Range of motion

an unstable knee

patients sensitive to materials of bovine origins

allergic to the antibiotic gentamicin

in children

yet in any joint other than the knee

AUTOLOGOUS CHONDROCYTEIMPLANTATION (ACI)

StrengthsCan produce hyaline-like cartilageCan fill defects regardless of size with functional repair tissueModerate to large defects that have failed previous interventionRepair tissue which matures rather than deteriorates over timeExpected outcomeReturn to previous level of functioning

ldquoBiological Joint replacementrdquo

LimitationsMore invasiveExpenseLonger recovery

A ACI ndash Periosteum (cells under periosteum)

B ACI ndash Chondrogide (cells under membrane)

C MACI ndash Matrix Induced ACI (cells on membrane)

Chondrogide Membrane Porcine type IIII Inert Seal Resorbs in 3-4 months

ACI MACI

TECHNIQUES

Under inert collagen membrane (ACI)

On inert collagen membrane (MACI)

Harvest 200-300mg full thickness cartilage from trochlea (non load bearing)

Cells grown on monolayer with patients serum

No cells x 20-30

ACIMACI GENERIC METHOD

ACI METHOD

TREATMENT WITH CARTICEL

Uses your own cartilage cells (chondrocytes) to repair the articular cartilage damage in your knee When implanted into a cartilage injury your own cells can form new cartilage this new cartilage is very similar to your original cartilage The CARTICEL implantation procedure is called Autologous Chondrocyte Implantation or ACI It is a two-step process

Knee Cartilage Arthroscopy and BiopsyDuring an arthroscopic procedure surgeon assesses the extent of cartilage damage amp pt as a candidate for CARTICEL implantation

ldquoBiopsyrdquo of healthy tissue about the size of a pencil eraser ie about 200 -300 mg

From outer edge of sup Med or lat Femoral condyle or inner edge of lat Femoral condyle at the intercondylar notch

This sample is sent to product labs

Step 1 Biopsy

Biopsy can be stored for up to two years so you can schedule your surgery at your convenience

When you are ready your cells are cultured over three to five weeks they increase to approx 12 million cells in a vial containing 03 ndash 04 cc of medium Every step of the manufacturing process is monitored to ensure high quality and safety

CARTICEL MANUFACTURING AND DELIVERY

STEP 2 IMPLANTATION

Cartilage Injury CleanedDuring this second stage arthrotomy done to expose knee and any dead or damaged tissue from the injury removed with curette leaving only healthy tissue

Biomachenical allignment procedures if required should be done in conjunction with implantation

CARTICEL IMPLANTATION

PERIOSTEAL PATCH

surgeon takes a small piece of tissue from your shin bone and sews it securely over the injury

CARTICEL Implantation surgeon injects CARTICEL under the patch

When CARTICEL is surgically implanted into a cartilage injury it can grow and form new hyaline-like cartilage with properties similar to those of the original cartilage

Repairing the injury helps to reduce pain and improve movement and function

ACI STEPS summarised

MACI METHOD

Cultured chondrocytes seeded in bilayered typeIIII collagen membrane

Implanted using fibrin glue

Matrix remodelled in months replaced by extracellular matrix regenerate

The overall failure rate is at present quoted as being 10 The two most common complications include bullloosening of the transplant tissue bullformation of fibrous tissue at the repair site and adhesions with return of pain and locking Neither of these complications usually leaves the patient in a worse condition than hisher pre-transplantation state

Other adverse events include bullpost-op haematoma (big blood clot)bullhypertrophic synovitis (angry knee) and superficial wound infection

COMPLICATIONS

IMPROVEMENTS IN CLINICAL OUTCOME

ASSESMENT OF TECHNIQUE

FOLLOW UP RESULTS

ONE YEAR ASSESSMENT

Radiographs Alignment Bone quality

MRI Healing

cartilage Graft failure

Arthroscopy + probe Graft integrity Pressure biopsy

FOLLOW UP BIOPSY

FOLLOW UP MRI

Final appearance of theperiosteum sutured overfemoral condyle defect Thecartilage cells have beeninjected under the flap and thefinal suture placed to close thecover and provide a watertightseal

FOLLOW UP ARTHROSCOPIC

Arthroscopic appearance of thesame area 12 months afterCarticeltrade implantation Thedefect is no longer visible andthere is now hyaline cartilage(biopsy proven) filling theoriginal defect site

REHABILITATION GUIDELINES

Immobilization first 12-24 hours

(CPM) after 12-24 hours for about 4 weeks

Complete joint loading from about 5th week trochleapatellafrom about 8th week condyle Back to sports Low impact rarr within 6 monthsRepeated impact rarr from 8th monthHigh impact rarr from 10-12th month

ACI REHABILITATION

Weight bearingIt is recommended to keep you in non-weight bearing until the second week after surgery (ACI) You can increase the weight bearing gradually and you may be able to sustain your full weight bearing after 6 to 12 weeks from surgery

Range of motionRecovery on your ROM (Range of Motion) is gradually increased with a continuous passive motion (CPM) machine and may be completed to 140 degrees of ROM at 6 weeks to 12 weeks after surgery

ACI REHABILITATIONIndoor exerciseYou can strenghthen your muscles surrounding the knee joint with a four point exercise as well as isometric hamstring and squatting exercises from 4 weeks to 6 weeks after surgeryYou may start performing stationary bike activity without resistance and increase the resistance gradually

Outdoor exerciseAt 13 weeks after surgery you can start walking lightly and at 10 months after surgery you can perform jogging and then you may enjoy intensity exercise like playing tennis or volleyball from 18 months after surgery

Rehabilitation Goals at 12 weeks after ACIFull ROM (Range of Motion) Minimal edema level Minimal occasional pain Pain free tolerance to transitional phase exercise with adequate stability and motor control

COMPARISON WITH OTHER METHODS OF TREATMENTS

Autologous Chondrocyte Implantation Aims to increase the best condition for cartilage defectAdvantagesbullHyaline cartilage is formed bullPermanent reconstructed cartilage tissue bullMost valuable treatment

bullWith Fourth Generation ACI Use of cell ndash gel mixture (collagen hyaluronic acid and fibrin) has fast gelling properties (1 ndash 5 min) upon transplantation bullNo membrane or periosteal patch bullMinimal surgical exposure and reduced surgery time bullCorrects evenly irregular defect shapes bullApplicable to larger defects

COMPARISON WITH OTHER METHODS OF TREATMENTShelliphelliphellip

Abrasion arthroplastyAims to decrease the inflammation of the jointDisadvantagesbullRemoves many cartilage fragments from the jointbullSymptoms reoccur within one year

Drilling and MicrofractureAims to generate a healing responseDisadvantagesbullThe healing response in inadequate bullNo hyaline cartilage is formed but rather fibrocartilage bullHas a limited lifespan of approximately one year bullRapid deterioration after such procedures can be expected

COMPARISON WITH OTHER METHODS OF TREATMENTShelliphelliphellip

Perichondral ResurfacingDisadvantagesbullIsolated cartilage defects are often too large to be covered byh perichondrum bullLong term follow-up of such procedures indicate that the implants undergo endochondral ossification

Synthetic Materials (ie Carbon Fiber Mesh)Disadvantagesbull It often results in fibrous tissue formation bullNot adequate biomechanically bullOften the cause for synovitis in the joints

Osteocartiloginous GraftsAims to reconstruct jointsDisadvantagesbullUnless fresh cartilage is transplanted the cartilage is dead bullFresh grafts are not commonly used as they inevitably carry a risk of disease transmission bullCyropreserved grafts can survive for many years but ultimately deteriorate

Results of the Carticeltrade procedure have been encouraging although it is not always successful An analysis was done of the US and Swedish registry of 153 consecutive patients undergoing this procedure with follow-up from 1 week to 94 months The following results were obtainedbull Patients with clinical improvement 85bull Good or Excellent results 42 bull Good or Excellent results at 2 yearspersisting at 5 years post-op 97

Thus a total of 85 of patients showed some or complete improvement with theimplantation technique The Carticel procedure demonstrated good durability at 5-10 years out

CONCLUSIONS

CONCLUSIONS ACI Vs MACI No current evidence to justify aggressive treatment of

asymptomatic lesions with ACIMACI

Patients with full thickness symptomatic defects do poorly if left untreated

ACI and MACI lead to significant improvement in objective and patient reported clinical outcome scores for up to ten years(even among those with previous failed marrow stimulation techniques)

MACI has a superior rate of clinical improvement in comparison to ACI

Repair tissue may remodel and improve in quality with time

ACI and MACI comparable at 6 years

RECENT ADVANCESHYAFF 3D MATRIX

HYAFF biomaterialscontain high quantities ofderivatized HA

HA-richchondrocyte compatibleembryonic-like mileuconductive to regenerativehealing patterns

bull Non woven felt 2 mm thick fiber diameter 10 micronsbull Chondrocytes are isolated and passaged in culture on plasticdishes up to 3 weeksbull Cells are seeded for 2 weeks on HYAFF scaffold at a density of1 x 106 cm2 resulting in a total of 4 x 106 cm2 seeded cells pergraft

HYAFF-BASED SCAFFOLD

CHONDRONtrade

Uses a cell ndash gel mixture (includes collagen hyaluronic acid and fibrin) that has fast gelling properties (1 ndash 5 min) upon transplantation

This cell and gel mixture enable even cell distribution three-dimensionally moldable to fit irregular defect shape and applicable to a larger defectThus there is minimal surgical exposure and reduced surgery time

(three-dimensional reconstruction of a chondron from the growth plate of the murine long bone the model was generated from multiple sections imaged in an electron microscope plasma membranes are coloured green and internal organelles are visible within the top cell)

RECOVERY TO

HEALTHY ACTIVE LIFE

THANK YOU

• journal club (22-10-09)
• topic autologus chondrocyte implantation
• THE ROLE OF AUTOLOGOUS CHONDROCYTE IMPLANTATION (ACI) IN THE TR
• Slide 4
• AUTOLOGOUS CHONDROCYTE GRAFTS MULTICENTRIC TRIAL WITH 28 KNEE
• Slide 6
• Slide 7
• Articular Cartilage
• Hyaline Cartilage Structure 1048715The ldquostuffrdquo of cartilage
• Slide 11
• Cartilage Injury Occurs in Many Forms
• Articular Cartilage Defects a treatment challenge
• AND WHAT IS IN OUR BASKET
• SO IT LED US TO SEARCH OF MORE PROMISING OPTION
• Autologous Chondrocyte Implantation (ACI) BACKGROUND
• Identifying a Carticelreg Patient
• Identifying a Carticelreg Patienthelliphellip
• Pre-requisite for surgery
• Autologous Chondrocyte Implantation (ACI)
• Techniques
• ACIMACI Generic Method
• Slide 23
• Treatment with CARTICEL
• CARTICEL Manufacturing and Delivery
• Step 2 Implantation
• CARTICEL Implantation
• Periosteal Patch
• Slide 29
• Slide 30
• Aci steps summarised
• Slide 32
• Complications
• Slide 34
• Slide 35
• FOLLOW UP Biopsy
• FOLLOW UP MRI
• FOLLOW UP ARTHROSCOPIC
• Rehabilitation guidelines
• ACI Rehabilitation
• ACI Rehabilitation (2)
• COMPARISON WITH OTHER METHODS OF TREATMENTS
• COMPARISON WITH OTHER METHODS OF TREATMENTShelliphelliphellip
• COMPARISON WITH OTHER METHODS OF TREATMENTShelliphelliphellip (2)
• CONCLUSIONS
• Slide 46
• Recent advancesHYAFF 3D matrix
• HYAFF-based Scaffold
• CHONDRONtrade
• RECOVERY TO
• Slide 51

AUTOLOGOUS CHONDROCYTE GRAFTS MULTICENTRIC TRIAL WITH 28 KNEE IMPLANTATIONS WITH MORE THAN TWO YEARS FOLLOW-UP

Journal of Bone and Joint Surgery - British Volume Vol 90-B Issue SUPP_II 252

Purpose of the study Spontaneous repair of lost deep chondral tissue is minimal in the knee joint A clinical trial of chondrocyte autografts as described by Brittberg and Peterson was undertaken by the Nantes University Hospital and the French Society of

Arthroscopy in 1999

Material and methods Twenty-eight patients mean age 28 years underwent surgery in eight centers Etiologies were

osteochondritis (n=14) isolated posttraumatic chondorpathy (n=7) chondropathy and full-thickness ACL tear (n=7)

All lesions involved the condyles and were deep (ICRS grds 3 and 4)

Mean surface area involved after debridement was 490 mm2 (range 150ndash1000 mm2)

Patients were followed three years after the autologous

grafting to assess functional outcome An MRI was obtained at 2ndash3 years Thirteen control arthroscopy procedures were performed

including eight with biopsy specimens for histology and

immunohisto-chemistry studies

RESULTS Twenty-six patients were reviewed at gt 2 yrs There were no general complications Three patients presented a partial avulsion of the graft treated by arthroscopy and

one underwent arthrolysis at six months FUNCTION improved in all patients except three and pain improved in all THE ICRS SCORE improved from 43 points (range 19ndash70) to 77 points (range 39ndash

84) Sixteen control MRIs were available and showed that

the graft was hypertrophic in eleven cases on level in four and insufficient in one Marginal integration was good in 11 cases and partial in five Subchondral integration was complete in ten cases and mediocre in six

THE ARTHROSCOPIC SCORE was nearly normal (score 8ndash11) in eight cases and

abnormal in five (score 4ndash7) THE HISTOLOGICAL CLASS according to Knutsen (hyaline richness) was

one in group 1 (gt60) three in group 2 (gt 40) four in group 3 (lt40) and one in group 4 (bony or fibrous tissue)

Function score (r=078 and MRI score (r=076) were correlated with arthroscopic sores There was no correlation with the histological results

DISCUSSION CLINICAL OUTCOME WAS IMPROVED IN MORE THAN 80 OF CASES SIMILAR TO RESULTS REPORTED FOR HISTOLOGICAL SERIES The arthroscopic and histological results were equivalent to those reported by Knutsen but inferior to those reported by Bentley or Peterson

ARTICULAR CARTILAGE

Chondrocytes (cartilage cells) embedded in a Highly specialised ECM

Gives elasticityProvides resistance to

tensilecompressive and shear forces

Acts as a smooth efficient surface for motion

HYALINE CARTILAGE STRUCTURE1048715THE ldquoSTUFFrdquo OF CARTILAGE

Functions of the Articular Cartilage ndash Distribute loadndash Absorb shock

CHONDRAL INJURIES

Deficient in type II collagen

Lower load bearing capacity

INEVITABLE lsquoSHORT TERMrsquo RECOVERY

Commonly these injuries heal by scar tissue formation

PREVALENCE AND INCIDENCE

993 consecutive arthroscopies ndash 66 articular cartilage pathology 11 full thickness localised lesions suitable for repair procedures

Aroen A Loken S Heir S et al Am J Sports Med 2004 32 211-15

31000 arthroscopic procedures ndash 63 articular cartilage lesions

Curl WW Krome J Gordon ES et al Arthroscopy 1997 13 456-60

1000 consecutive arthroscopies ndash 19 localised chondralosteochondral lesionsHjelle K et al Arthroscopy 2002 18 730-4

CARTILAGE INJURY OCCURS IN MANY FORMS

Trauma sports or work related

Chronic instability long term effects ACL and othermeniscal deficiency

Mal-aligned joint - deformityvarus Valgus

Osteochondritis Dissecans [OCD]

Genetic pre-disposition earlyarthritis

bull Most full-thickness defects are symptomaticndash Pain swelling locking catching grinding

bull Left untreatedmay progress to significant articular defects

ARTICULAR CARTILAGE DEFECTS A TREATMENT CHALLENGE

bullMay lead to debilitatingosteoarthritis

Arthroscopic Debridement

Arthroscopic lavage

Subchondral drilling

Microfracture MARROW STIMULATION TECHNIQUES Abrasion arthroplasty -to induce the growth of fibrocartilage into the chondral defect (This fibrocartilage does not withstand shock or shearing force as well as the original hyaline cartilage and may deteriorate over time)

AND WHAT IS IN OUR BASKET

AUTOLOGUS CHONDROCYTE IMPLANTATION

SO IT LED US TO SEARCH OF MORE PROMISING OPTION

JBJS [Am] 1987 Peterson et al Gothenburgndash first application of cell engineering in orthopaedics

NEJM 1994 Brittberg et al Swedenndash successfuly regenerated hyaline-like cartilage in isolated chondral defects

AUTOLOGOUS CHONDROCYTE IMPLANTATION (ACI) BACKGROUND

IDENTIFYING A CARTICELreg PATIENT

Patient FactorsYounger patients ndash lt age 45 - 50 (avg ~ 35 yo)

Significant impairment-Compromised daily livingactivities -Refractory to treatment

Obesity

Demanding Physical activities

Willing amp capable of rehabilitation program

IDENTIFYING A CARTICELreg PATIENThelliphellip

Joint FactorsSymptomatic cartilage defects -Moderate to large (gt 2cm2 d= 16) -On the distal femur (mfc lfc trochlea) -Average defect size gt 4 cm2

-Either chondral or osteochondral

Relatively healthy joint ndash -No arthritis

Co-morbidities(meniscal tear

instability or malalignment) must be corrected prior or concurrent to implantation

Pre-requisite for surgery

Not recommended for patients who have

Appropriate biomachenical alignment

Ligamentous stabilty

Range of motion

an unstable knee

patients sensitive to materials of bovine origins

allergic to the antibiotic gentamicin

in children

yet in any joint other than the knee

AUTOLOGOUS CHONDROCYTEIMPLANTATION (ACI)

StrengthsCan produce hyaline-like cartilageCan fill defects regardless of size with functional repair tissueModerate to large defects that have failed previous interventionRepair tissue which matures rather than deteriorates over timeExpected outcomeReturn to previous level of functioning

ldquoBiological Joint replacementrdquo

LimitationsMore invasiveExpenseLonger recovery

A ACI ndash Periosteum (cells under periosteum)

B ACI ndash Chondrogide (cells under membrane)

C MACI ndash Matrix Induced ACI (cells on membrane)

Chondrogide Membrane Porcine type IIII Inert Seal Resorbs in 3-4 months

ACI MACI

TECHNIQUES

Under inert collagen membrane (ACI)

On inert collagen membrane (MACI)

Harvest 200-300mg full thickness cartilage from trochlea (non load bearing)

Cells grown on monolayer with patients serum

No cells x 20-30

ACIMACI GENERIC METHOD

ACI METHOD

TREATMENT WITH CARTICEL

Uses your own cartilage cells (chondrocytes) to repair the articular cartilage damage in your knee When implanted into a cartilage injury your own cells can form new cartilage this new cartilage is very similar to your original cartilage The CARTICEL implantation procedure is called Autologous Chondrocyte Implantation or ACI It is a two-step process

Knee Cartilage Arthroscopy and BiopsyDuring an arthroscopic procedure surgeon assesses the extent of cartilage damage amp pt as a candidate for CARTICEL implantation

ldquoBiopsyrdquo of healthy tissue about the size of a pencil eraser ie about 200 -300 mg

From outer edge of sup Med or lat Femoral condyle or inner edge of lat Femoral condyle at the intercondylar notch

This sample is sent to product labs

Step 1 Biopsy

Biopsy can be stored for up to two years so you can schedule your surgery at your convenience

When you are ready your cells are cultured over three to five weeks they increase to approx 12 million cells in a vial containing 03 ndash 04 cc of medium Every step of the manufacturing process is monitored to ensure high quality and safety

CARTICEL MANUFACTURING AND DELIVERY

STEP 2 IMPLANTATION

Cartilage Injury CleanedDuring this second stage arthrotomy done to expose knee and any dead or damaged tissue from the injury removed with curette leaving only healthy tissue

Biomachenical allignment procedures if required should be done in conjunction with implantation

CARTICEL IMPLANTATION

PERIOSTEAL PATCH

surgeon takes a small piece of tissue from your shin bone and sews it securely over the injury

CARTICEL Implantation surgeon injects CARTICEL under the patch

When CARTICEL is surgically implanted into a cartilage injury it can grow and form new hyaline-like cartilage with properties similar to those of the original cartilage

Repairing the injury helps to reduce pain and improve movement and function

ACI STEPS summarised

MACI METHOD

Cultured chondrocytes seeded in bilayered typeIIII collagen membrane

Implanted using fibrin glue

Matrix remodelled in months replaced by extracellular matrix regenerate

The overall failure rate is at present quoted as being 10 The two most common complications include bullloosening of the transplant tissue bullformation of fibrous tissue at the repair site and adhesions with return of pain and locking Neither of these complications usually leaves the patient in a worse condition than hisher pre-transplantation state

Other adverse events include bullpost-op haematoma (big blood clot)bullhypertrophic synovitis (angry knee) and superficial wound infection

COMPLICATIONS

IMPROVEMENTS IN CLINICAL OUTCOME

ASSESMENT OF TECHNIQUE

FOLLOW UP RESULTS

ONE YEAR ASSESSMENT

Radiographs Alignment Bone quality

MRI Healing

cartilage Graft failure

Arthroscopy + probe Graft integrity Pressure biopsy

FOLLOW UP BIOPSY

FOLLOW UP MRI

Final appearance of theperiosteum sutured overfemoral condyle defect Thecartilage cells have beeninjected under the flap and thefinal suture placed to close thecover and provide a watertightseal

FOLLOW UP ARTHROSCOPIC

Arthroscopic appearance of thesame area 12 months afterCarticeltrade implantation Thedefect is no longer visible andthere is now hyaline cartilage(biopsy proven) filling theoriginal defect site

REHABILITATION GUIDELINES

Immobilization first 12-24 hours

(CPM) after 12-24 hours for about 4 weeks

Complete joint loading from about 5th week trochleapatellafrom about 8th week condyle Back to sports Low impact rarr within 6 monthsRepeated impact rarr from 8th monthHigh impact rarr from 10-12th month

ACI REHABILITATION

Weight bearingIt is recommended to keep you in non-weight bearing until the second week after surgery (ACI) You can increase the weight bearing gradually and you may be able to sustain your full weight bearing after 6 to 12 weeks from surgery

Range of motionRecovery on your ROM (Range of Motion) is gradually increased with a continuous passive motion (CPM) machine and may be completed to 140 degrees of ROM at 6 weeks to 12 weeks after surgery

ACI REHABILITATIONIndoor exerciseYou can strenghthen your muscles surrounding the knee joint with a four point exercise as well as isometric hamstring and squatting exercises from 4 weeks to 6 weeks after surgeryYou may start performing stationary bike activity without resistance and increase the resistance gradually

Outdoor exerciseAt 13 weeks after surgery you can start walking lightly and at 10 months after surgery you can perform jogging and then you may enjoy intensity exercise like playing tennis or volleyball from 18 months after surgery

Rehabilitation Goals at 12 weeks after ACIFull ROM (Range of Motion) Minimal edema level Minimal occasional pain Pain free tolerance to transitional phase exercise with adequate stability and motor control

COMPARISON WITH OTHER METHODS OF TREATMENTS

Autologous Chondrocyte Implantation Aims to increase the best condition for cartilage defectAdvantagesbullHyaline cartilage is formed bullPermanent reconstructed cartilage tissue bullMost valuable treatment

bullWith Fourth Generation ACI Use of cell ndash gel mixture (collagen hyaluronic acid and fibrin) has fast gelling properties (1 ndash 5 min) upon transplantation bullNo membrane or periosteal patch bullMinimal surgical exposure and reduced surgery time bullCorrects evenly irregular defect shapes bullApplicable to larger defects

COMPARISON WITH OTHER METHODS OF TREATMENTShelliphelliphellip

Abrasion arthroplastyAims to decrease the inflammation of the jointDisadvantagesbullRemoves many cartilage fragments from the jointbullSymptoms reoccur within one year

Drilling and MicrofractureAims to generate a healing responseDisadvantagesbullThe healing response in inadequate bullNo hyaline cartilage is formed but rather fibrocartilage bullHas a limited lifespan of approximately one year bullRapid deterioration after such procedures can be expected

COMPARISON WITH OTHER METHODS OF TREATMENTShelliphelliphellip

Perichondral ResurfacingDisadvantagesbullIsolated cartilage defects are often too large to be covered byh perichondrum bullLong term follow-up of such procedures indicate that the implants undergo endochondral ossification

Synthetic Materials (ie Carbon Fiber Mesh)Disadvantagesbull It often results in fibrous tissue formation bullNot adequate biomechanically bullOften the cause for synovitis in the joints

Osteocartiloginous GraftsAims to reconstruct jointsDisadvantagesbullUnless fresh cartilage is transplanted the cartilage is dead bullFresh grafts are not commonly used as they inevitably carry a risk of disease transmission bullCyropreserved grafts can survive for many years but ultimately deteriorate

Results of the Carticeltrade procedure have been encouraging although it is not always successful An analysis was done of the US and Swedish registry of 153 consecutive patients undergoing this procedure with follow-up from 1 week to 94 months The following results were obtainedbull Patients with clinical improvement 85bull Good or Excellent results 42 bull Good or Excellent results at 2 yearspersisting at 5 years post-op 97

Thus a total of 85 of patients showed some or complete improvement with theimplantation technique The Carticel procedure demonstrated good durability at 5-10 years out

CONCLUSIONS

CONCLUSIONS ACI Vs MACI No current evidence to justify aggressive treatment of

asymptomatic lesions with ACIMACI

Patients with full thickness symptomatic defects do poorly if left untreated

ACI and MACI lead to significant improvement in objective and patient reported clinical outcome scores for up to ten years(even among those with previous failed marrow stimulation techniques)

MACI has a superior rate of clinical improvement in comparison to ACI

Repair tissue may remodel and improve in quality with time

ACI and MACI comparable at 6 years

RECENT ADVANCESHYAFF 3D MATRIX

HYAFF biomaterialscontain high quantities ofderivatized HA

HA-richchondrocyte compatibleembryonic-like mileuconductive to regenerativehealing patterns

bull Non woven felt 2 mm thick fiber diameter 10 micronsbull Chondrocytes are isolated and passaged in culture on plasticdishes up to 3 weeksbull Cells are seeded for 2 weeks on HYAFF scaffold at a density of1 x 106 cm2 resulting in a total of 4 x 106 cm2 seeded cells pergraft

HYAFF-BASED SCAFFOLD

CHONDRONtrade

Uses a cell ndash gel mixture (includes collagen hyaluronic acid and fibrin) that has fast gelling properties (1 ndash 5 min) upon transplantation

This cell and gel mixture enable even cell distribution three-dimensionally moldable to fit irregular defect shape and applicable to a larger defectThus there is minimal surgical exposure and reduced surgery time

(three-dimensional reconstruction of a chondron from the growth plate of the murine long bone the model was generated from multiple sections imaged in an electron microscope plasma membranes are coloured green and internal organelles are visible within the top cell)

RECOVERY TO

HEALTHY ACTIVE LIFE

THANK YOU

• journal club (22-10-09)
• topic autologus chondrocyte implantation
• THE ROLE OF AUTOLOGOUS CHONDROCYTE IMPLANTATION (ACI) IN THE TR
• Slide 4
• AUTOLOGOUS CHONDROCYTE GRAFTS MULTICENTRIC TRIAL WITH 28 KNEE
• Slide 6
• Slide 7
• Articular Cartilage
• Hyaline Cartilage Structure 1048715The ldquostuffrdquo of cartilage
• Slide 11
• Cartilage Injury Occurs in Many Forms
• Articular Cartilage Defects a treatment challenge
• AND WHAT IS IN OUR BASKET
• SO IT LED US TO SEARCH OF MORE PROMISING OPTION
• Autologous Chondrocyte Implantation (ACI) BACKGROUND
• Identifying a Carticelreg Patient
• Identifying a Carticelreg Patienthelliphellip
• Pre-requisite for surgery
• Autologous Chondrocyte Implantation (ACI)
• Techniques
• ACIMACI Generic Method
• Slide 23
• Treatment with CARTICEL
• CARTICEL Manufacturing and Delivery
• Step 2 Implantation
• CARTICEL Implantation
• Periosteal Patch
• Slide 29
• Slide 30
• Aci steps summarised
• Slide 32
• Complications
• Slide 34
• Slide 35
• FOLLOW UP Biopsy
• FOLLOW UP MRI
• FOLLOW UP ARTHROSCOPIC
• Rehabilitation guidelines
• ACI Rehabilitation
• ACI Rehabilitation (2)
• COMPARISON WITH OTHER METHODS OF TREATMENTS
• COMPARISON WITH OTHER METHODS OF TREATMENTShelliphelliphellip
• COMPARISON WITH OTHER METHODS OF TREATMENTShelliphelliphellip (2)
• CONCLUSIONS
• Slide 46
• Recent advancesHYAFF 3D matrix
• HYAFF-based Scaffold
• CHONDRONtrade
• RECOVERY TO
• Slide 51

Material and methods Twenty-eight patients mean age 28 years underwent surgery in eight centers Etiologies were

osteochondritis (n=14) isolated posttraumatic chondorpathy (n=7) chondropathy and full-thickness ACL tear (n=7)

All lesions involved the condyles and were deep (ICRS grds 3 and 4)

Mean surface area involved after debridement was 490 mm2 (range 150ndash1000 mm2)

Patients were followed three years after the autologous

grafting to assess functional outcome An MRI was obtained at 2ndash3 years Thirteen control arthroscopy procedures were performed

including eight with biopsy specimens for histology and

immunohisto-chemistry studies

RESULTS Twenty-six patients were reviewed at gt 2 yrs There were no general complications Three patients presented a partial avulsion of the graft treated by arthroscopy and

one underwent arthrolysis at six months FUNCTION improved in all patients except three and pain improved in all THE ICRS SCORE improved from 43 points (range 19ndash70) to 77 points (range 39ndash

84) Sixteen control MRIs were available and showed that

the graft was hypertrophic in eleven cases on level in four and insufficient in one Marginal integration was good in 11 cases and partial in five Subchondral integration was complete in ten cases and mediocre in six

THE ARTHROSCOPIC SCORE was nearly normal (score 8ndash11) in eight cases and

abnormal in five (score 4ndash7) THE HISTOLOGICAL CLASS according to Knutsen (hyaline richness) was

one in group 1 (gt60) three in group 2 (gt 40) four in group 3 (lt40) and one in group 4 (bony or fibrous tissue)

Function score (r=078 and MRI score (r=076) were correlated with arthroscopic sores There was no correlation with the histological results

DISCUSSION CLINICAL OUTCOME WAS IMPROVED IN MORE THAN 80 OF CASES SIMILAR TO RESULTS REPORTED FOR HISTOLOGICAL SERIES The arthroscopic and histological results were equivalent to those reported by Knutsen but inferior to those reported by Bentley or Peterson

ARTICULAR CARTILAGE

Chondrocytes (cartilage cells) embedded in a Highly specialised ECM

Gives elasticityProvides resistance to

tensilecompressive and shear forces

Acts as a smooth efficient surface for motion

HYALINE CARTILAGE STRUCTURE1048715THE ldquoSTUFFrdquo OF CARTILAGE

Functions of the Articular Cartilage ndash Distribute loadndash Absorb shock

CHONDRAL INJURIES

Deficient in type II collagen

Lower load bearing capacity

INEVITABLE lsquoSHORT TERMrsquo RECOVERY

Commonly these injuries heal by scar tissue formation

PREVALENCE AND INCIDENCE

993 consecutive arthroscopies ndash 66 articular cartilage pathology 11 full thickness localised lesions suitable for repair procedures

Aroen A Loken S Heir S et al Am J Sports Med 2004 32 211-15

31000 arthroscopic procedures ndash 63 articular cartilage lesions

Curl WW Krome J Gordon ES et al Arthroscopy 1997 13 456-60

1000 consecutive arthroscopies ndash 19 localised chondralosteochondral lesionsHjelle K et al Arthroscopy 2002 18 730-4

CARTILAGE INJURY OCCURS IN MANY FORMS

Trauma sports or work related

Chronic instability long term effects ACL and othermeniscal deficiency

Mal-aligned joint - deformityvarus Valgus

Osteochondritis Dissecans [OCD]

Genetic pre-disposition earlyarthritis

bull Most full-thickness defects are symptomaticndash Pain swelling locking catching grinding

bull Left untreatedmay progress to significant articular defects

ARTICULAR CARTILAGE DEFECTS A TREATMENT CHALLENGE

bullMay lead to debilitatingosteoarthritis

Arthroscopic Debridement

Arthroscopic lavage

Subchondral drilling

Microfracture MARROW STIMULATION TECHNIQUES Abrasion arthroplasty -to induce the growth of fibrocartilage into the chondral defect (This fibrocartilage does not withstand shock or shearing force as well as the original hyaline cartilage and may deteriorate over time)

AND WHAT IS IN OUR BASKET

AUTOLOGUS CHONDROCYTE IMPLANTATION

SO IT LED US TO SEARCH OF MORE PROMISING OPTION

JBJS [Am] 1987 Peterson et al Gothenburgndash first application of cell engineering in orthopaedics

NEJM 1994 Brittberg et al Swedenndash successfuly regenerated hyaline-like cartilage in isolated chondral defects

AUTOLOGOUS CHONDROCYTE IMPLANTATION (ACI) BACKGROUND

IDENTIFYING A CARTICELreg PATIENT

Patient FactorsYounger patients ndash lt age 45 - 50 (avg ~ 35 yo)

Significant impairment-Compromised daily livingactivities -Refractory to treatment

Obesity

Demanding Physical activities

Willing amp capable of rehabilitation program

IDENTIFYING A CARTICELreg PATIENThelliphellip

Joint FactorsSymptomatic cartilage defects -Moderate to large (gt 2cm2 d= 16) -On the distal femur (mfc lfc trochlea) -Average defect size gt 4 cm2

-Either chondral or osteochondral

Relatively healthy joint ndash -No arthritis

Co-morbidities(meniscal tear

instability or malalignment) must be corrected prior or concurrent to implantation

Pre-requisite for surgery

Not recommended for patients who have

Appropriate biomachenical alignment

Ligamentous stabilty

Range of motion

an unstable knee

patients sensitive to materials of bovine origins

allergic to the antibiotic gentamicin

in children

yet in any joint other than the knee

AUTOLOGOUS CHONDROCYTEIMPLANTATION (ACI)

StrengthsCan produce hyaline-like cartilageCan fill defects regardless of size with functional repair tissueModerate to large defects that have failed previous interventionRepair tissue which matures rather than deteriorates over timeExpected outcomeReturn to previous level of functioning

ldquoBiological Joint replacementrdquo

LimitationsMore invasiveExpenseLonger recovery

A ACI ndash Periosteum (cells under periosteum)

B ACI ndash Chondrogide (cells under membrane)

C MACI ndash Matrix Induced ACI (cells on membrane)

Chondrogide Membrane Porcine type IIII Inert Seal Resorbs in 3-4 months

ACI MACI

TECHNIQUES

Under inert collagen membrane (ACI)

On inert collagen membrane (MACI)

Harvest 200-300mg full thickness cartilage from trochlea (non load bearing)

Cells grown on monolayer with patients serum

No cells x 20-30

ACIMACI GENERIC METHOD

ACI METHOD

TREATMENT WITH CARTICEL

Uses your own cartilage cells (chondrocytes) to repair the articular cartilage damage in your knee When implanted into a cartilage injury your own cells can form new cartilage this new cartilage is very similar to your original cartilage The CARTICEL implantation procedure is called Autologous Chondrocyte Implantation or ACI It is a two-step process

Knee Cartilage Arthroscopy and BiopsyDuring an arthroscopic procedure surgeon assesses the extent of cartilage damage amp pt as a candidate for CARTICEL implantation

ldquoBiopsyrdquo of healthy tissue about the size of a pencil eraser ie about 200 -300 mg

From outer edge of sup Med or lat Femoral condyle or inner edge of lat Femoral condyle at the intercondylar notch

This sample is sent to product labs

Step 1 Biopsy

Biopsy can be stored for up to two years so you can schedule your surgery at your convenience

When you are ready your cells are cultured over three to five weeks they increase to approx 12 million cells in a vial containing 03 ndash 04 cc of medium Every step of the manufacturing process is monitored to ensure high quality and safety

CARTICEL MANUFACTURING AND DELIVERY

STEP 2 IMPLANTATION

Cartilage Injury CleanedDuring this second stage arthrotomy done to expose knee and any dead or damaged tissue from the injury removed with curette leaving only healthy tissue

Biomachenical allignment procedures if required should be done in conjunction with implantation

CARTICEL IMPLANTATION

PERIOSTEAL PATCH

surgeon takes a small piece of tissue from your shin bone and sews it securely over the injury

CARTICEL Implantation surgeon injects CARTICEL under the patch

When CARTICEL is surgically implanted into a cartilage injury it can grow and form new hyaline-like cartilage with properties similar to those of the original cartilage

Repairing the injury helps to reduce pain and improve movement and function

ACI STEPS summarised

MACI METHOD

Cultured chondrocytes seeded in bilayered typeIIII collagen membrane

Implanted using fibrin glue

Matrix remodelled in months replaced by extracellular matrix regenerate

The overall failure rate is at present quoted as being 10 The two most common complications include bullloosening of the transplant tissue bullformation of fibrous tissue at the repair site and adhesions with return of pain and locking Neither of these complications usually leaves the patient in a worse condition than hisher pre-transplantation state

Other adverse events include bullpost-op haematoma (big blood clot)bullhypertrophic synovitis (angry knee) and superficial wound infection

COMPLICATIONS

IMPROVEMENTS IN CLINICAL OUTCOME

ASSESMENT OF TECHNIQUE

FOLLOW UP RESULTS

ONE YEAR ASSESSMENT

Radiographs Alignment Bone quality

MRI Healing

cartilage Graft failure

Arthroscopy + probe Graft integrity Pressure biopsy

FOLLOW UP BIOPSY

FOLLOW UP MRI

Final appearance of theperiosteum sutured overfemoral condyle defect Thecartilage cells have beeninjected under the flap and thefinal suture placed to close thecover and provide a watertightseal

FOLLOW UP ARTHROSCOPIC

Arthroscopic appearance of thesame area 12 months afterCarticeltrade implantation Thedefect is no longer visible andthere is now hyaline cartilage(biopsy proven) filling theoriginal defect site

REHABILITATION GUIDELINES

Immobilization first 12-24 hours

(CPM) after 12-24 hours for about 4 weeks

Complete joint loading from about 5th week trochleapatellafrom about 8th week condyle Back to sports Low impact rarr within 6 monthsRepeated impact rarr from 8th monthHigh impact rarr from 10-12th month

ACI REHABILITATION

Weight bearingIt is recommended to keep you in non-weight bearing until the second week after surgery (ACI) You can increase the weight bearing gradually and you may be able to sustain your full weight bearing after 6 to 12 weeks from surgery

Range of motionRecovery on your ROM (Range of Motion) is gradually increased with a continuous passive motion (CPM) machine and may be completed to 140 degrees of ROM at 6 weeks to 12 weeks after surgery

ACI REHABILITATIONIndoor exerciseYou can strenghthen your muscles surrounding the knee joint with a four point exercise as well as isometric hamstring and squatting exercises from 4 weeks to 6 weeks after surgeryYou may start performing stationary bike activity without resistance and increase the resistance gradually

Outdoor exerciseAt 13 weeks after surgery you can start walking lightly and at 10 months after surgery you can perform jogging and then you may enjoy intensity exercise like playing tennis or volleyball from 18 months after surgery

Rehabilitation Goals at 12 weeks after ACIFull ROM (Range of Motion) Minimal edema level Minimal occasional pain Pain free tolerance to transitional phase exercise with adequate stability and motor control

COMPARISON WITH OTHER METHODS OF TREATMENTS

Autologous Chondrocyte Implantation Aims to increase the best condition for cartilage defectAdvantagesbullHyaline cartilage is formed bullPermanent reconstructed cartilage tissue bullMost valuable treatment

bullWith Fourth Generation ACI Use of cell ndash gel mixture (collagen hyaluronic acid and fibrin) has fast gelling properties (1 ndash 5 min) upon transplantation bullNo membrane or periosteal patch bullMinimal surgical exposure and reduced surgery time bullCorrects evenly irregular defect shapes bullApplicable to larger defects

COMPARISON WITH OTHER METHODS OF TREATMENTShelliphelliphellip

Abrasion arthroplastyAims to decrease the inflammation of the jointDisadvantagesbullRemoves many cartilage fragments from the jointbullSymptoms reoccur within one year

Drilling and MicrofractureAims to generate a healing responseDisadvantagesbullThe healing response in inadequate bullNo hyaline cartilage is formed but rather fibrocartilage bullHas a limited lifespan of approximately one year bullRapid deterioration after such procedures can be expected

COMPARISON WITH OTHER METHODS OF TREATMENTShelliphelliphellip

Perichondral ResurfacingDisadvantagesbullIsolated cartilage defects are often too large to be covered byh perichondrum bullLong term follow-up of such procedures indicate that the implants undergo endochondral ossification

Synthetic Materials (ie Carbon Fiber Mesh)Disadvantagesbull It often results in fibrous tissue formation bullNot adequate biomechanically bullOften the cause for synovitis in the joints

Osteocartiloginous GraftsAims to reconstruct jointsDisadvantagesbullUnless fresh cartilage is transplanted the cartilage is dead bullFresh grafts are not commonly used as they inevitably carry a risk of disease transmission bullCyropreserved grafts can survive for many years but ultimately deteriorate

Results of the Carticeltrade procedure have been encouraging although it is not always successful An analysis was done of the US and Swedish registry of 153 consecutive patients undergoing this procedure with follow-up from 1 week to 94 months The following results were obtainedbull Patients with clinical improvement 85bull Good or Excellent results 42 bull Good or Excellent results at 2 yearspersisting at 5 years post-op 97

Thus a total of 85 of patients showed some or complete improvement with theimplantation technique The Carticel procedure demonstrated good durability at 5-10 years out

CONCLUSIONS

CONCLUSIONS ACI Vs MACI No current evidence to justify aggressive treatment of

asymptomatic lesions with ACIMACI

Patients with full thickness symptomatic defects do poorly if left untreated

ACI and MACI lead to significant improvement in objective and patient reported clinical outcome scores for up to ten years(even among those with previous failed marrow stimulation techniques)

MACI has a superior rate of clinical improvement in comparison to ACI

Repair tissue may remodel and improve in quality with time

ACI and MACI comparable at 6 years

RECENT ADVANCESHYAFF 3D MATRIX

HYAFF biomaterialscontain high quantities ofderivatized HA

HA-richchondrocyte compatibleembryonic-like mileuconductive to regenerativehealing patterns

bull Non woven felt 2 mm thick fiber diameter 10 micronsbull Chondrocytes are isolated and passaged in culture on plasticdishes up to 3 weeksbull Cells are seeded for 2 weeks on HYAFF scaffold at a density of1 x 106 cm2 resulting in a total of 4 x 106 cm2 seeded cells pergraft

HYAFF-BASED SCAFFOLD

CHONDRONtrade

Uses a cell ndash gel mixture (includes collagen hyaluronic acid and fibrin) that has fast gelling properties (1 ndash 5 min) upon transplantation

This cell and gel mixture enable even cell distribution three-dimensionally moldable to fit irregular defect shape and applicable to a larger defectThus there is minimal surgical exposure and reduced surgery time

(three-dimensional reconstruction of a chondron from the growth plate of the murine long bone the model was generated from multiple sections imaged in an electron microscope plasma membranes are coloured green and internal organelles are visible within the top cell)

RECOVERY TO

HEALTHY ACTIVE LIFE

THANK YOU

• journal club (22-10-09)
• topic autologus chondrocyte implantation
• THE ROLE OF AUTOLOGOUS CHONDROCYTE IMPLANTATION (ACI) IN THE TR
• Slide 4
• AUTOLOGOUS CHONDROCYTE GRAFTS MULTICENTRIC TRIAL WITH 28 KNEE
• Slide 6
• Slide 7
• Articular Cartilage
• Hyaline Cartilage Structure 1048715The ldquostuffrdquo of cartilage
• Slide 11
• Cartilage Injury Occurs in Many Forms
• Articular Cartilage Defects a treatment challenge
• AND WHAT IS IN OUR BASKET
• SO IT LED US TO SEARCH OF MORE PROMISING OPTION
• Autologous Chondrocyte Implantation (ACI) BACKGROUND
• Identifying a Carticelreg Patient
• Identifying a Carticelreg Patienthelliphellip
• Pre-requisite for surgery
• Autologous Chondrocyte Implantation (ACI)
• Techniques
• ACIMACI Generic Method
• Slide 23
• Treatment with CARTICEL
• CARTICEL Manufacturing and Delivery
• Step 2 Implantation
• CARTICEL Implantation
• Periosteal Patch
• Slide 29
• Slide 30
• Aci steps summarised
• Slide 32
• Complications
• Slide 34
• Slide 35
• FOLLOW UP Biopsy
• FOLLOW UP MRI
• FOLLOW UP ARTHROSCOPIC
• Rehabilitation guidelines
• ACI Rehabilitation
• ACI Rehabilitation (2)
• COMPARISON WITH OTHER METHODS OF TREATMENTS
• COMPARISON WITH OTHER METHODS OF TREATMENTShelliphelliphellip
• COMPARISON WITH OTHER METHODS OF TREATMENTShelliphelliphellip (2)
• CONCLUSIONS
• Slide 46
• Recent advancesHYAFF 3D matrix
• HYAFF-based Scaffold
• CHONDRONtrade
• RECOVERY TO
• Slide 51

RESULTS Twenty-six patients were reviewed at gt 2 yrs There were no general complications Three patients presented a partial avulsion of the graft treated by arthroscopy and

one underwent arthrolysis at six months FUNCTION improved in all patients except three and pain improved in all THE ICRS SCORE improved from 43 points (range 19ndash70) to 77 points (range 39ndash

84) Sixteen control MRIs were available and showed that

the graft was hypertrophic in eleven cases on level in four and insufficient in one Marginal integration was good in 11 cases and partial in five Subchondral integration was complete in ten cases and mediocre in six

THE ARTHROSCOPIC SCORE was nearly normal (score 8ndash11) in eight cases and

abnormal in five (score 4ndash7) THE HISTOLOGICAL CLASS according to Knutsen (hyaline richness) was

one in group 1 (gt60) three in group 2 (gt 40) four in group 3 (lt40) and one in group 4 (bony or fibrous tissue)

Function score (r=078 and MRI score (r=076) were correlated with arthroscopic sores There was no correlation with the histological results

DISCUSSION CLINICAL OUTCOME WAS IMPROVED IN MORE THAN 80 OF CASES SIMILAR TO RESULTS REPORTED FOR HISTOLOGICAL SERIES The arthroscopic and histological results were equivalent to those reported by Knutsen but inferior to those reported by Bentley or Peterson

ARTICULAR CARTILAGE

Chondrocytes (cartilage cells) embedded in a Highly specialised ECM

Gives elasticityProvides resistance to

tensilecompressive and shear forces

Acts as a smooth efficient surface for motion

HYALINE CARTILAGE STRUCTURE1048715THE ldquoSTUFFrdquo OF CARTILAGE

Functions of the Articular Cartilage ndash Distribute loadndash Absorb shock

CHONDRAL INJURIES

Deficient in type II collagen

Lower load bearing capacity

INEVITABLE lsquoSHORT TERMrsquo RECOVERY

Commonly these injuries heal by scar tissue formation

PREVALENCE AND INCIDENCE

993 consecutive arthroscopies ndash 66 articular cartilage pathology 11 full thickness localised lesions suitable for repair procedures

Aroen A Loken S Heir S et al Am J Sports Med 2004 32 211-15

31000 arthroscopic procedures ndash 63 articular cartilage lesions

Curl WW Krome J Gordon ES et al Arthroscopy 1997 13 456-60

1000 consecutive arthroscopies ndash 19 localised chondralosteochondral lesionsHjelle K et al Arthroscopy 2002 18 730-4

CARTILAGE INJURY OCCURS IN MANY FORMS

Trauma sports or work related

Chronic instability long term effects ACL and othermeniscal deficiency

Mal-aligned joint - deformityvarus Valgus

Osteochondritis Dissecans [OCD]

Genetic pre-disposition earlyarthritis

bull Most full-thickness defects are symptomaticndash Pain swelling locking catching grinding

bull Left untreatedmay progress to significant articular defects

ARTICULAR CARTILAGE DEFECTS A TREATMENT CHALLENGE

bullMay lead to debilitatingosteoarthritis

Arthroscopic Debridement

Arthroscopic lavage

Subchondral drilling

Microfracture MARROW STIMULATION TECHNIQUES Abrasion arthroplasty -to induce the growth of fibrocartilage into the chondral defect (This fibrocartilage does not withstand shock or shearing force as well as the original hyaline cartilage and may deteriorate over time)

AND WHAT IS IN OUR BASKET

AUTOLOGUS CHONDROCYTE IMPLANTATION

SO IT LED US TO SEARCH OF MORE PROMISING OPTION

JBJS [Am] 1987 Peterson et al Gothenburgndash first application of cell engineering in orthopaedics

NEJM 1994 Brittberg et al Swedenndash successfuly regenerated hyaline-like cartilage in isolated chondral defects

AUTOLOGOUS CHONDROCYTE IMPLANTATION (ACI) BACKGROUND

IDENTIFYING A CARTICELreg PATIENT

Patient FactorsYounger patients ndash lt age 45 - 50 (avg ~ 35 yo)

Significant impairment-Compromised daily livingactivities -Refractory to treatment

Obesity

Demanding Physical activities

Willing amp capable of rehabilitation program

IDENTIFYING A CARTICELreg PATIENThelliphellip

Joint FactorsSymptomatic cartilage defects -Moderate to large (gt 2cm2 d= 16) -On the distal femur (mfc lfc trochlea) -Average defect size gt 4 cm2

-Either chondral or osteochondral

Relatively healthy joint ndash -No arthritis

Co-morbidities(meniscal tear

instability or malalignment) must be corrected prior or concurrent to implantation

Pre-requisite for surgery

Not recommended for patients who have

Appropriate biomachenical alignment

Ligamentous stabilty

Range of motion

an unstable knee

patients sensitive to materials of bovine origins

allergic to the antibiotic gentamicin

in children

yet in any joint other than the knee

AUTOLOGOUS CHONDROCYTEIMPLANTATION (ACI)

StrengthsCan produce hyaline-like cartilageCan fill defects regardless of size with functional repair tissueModerate to large defects that have failed previous interventionRepair tissue which matures rather than deteriorates over timeExpected outcomeReturn to previous level of functioning

ldquoBiological Joint replacementrdquo

LimitationsMore invasiveExpenseLonger recovery

A ACI ndash Periosteum (cells under periosteum)

B ACI ndash Chondrogide (cells under membrane)

C MACI ndash Matrix Induced ACI (cells on membrane)

Chondrogide Membrane Porcine type IIII Inert Seal Resorbs in 3-4 months

ACI MACI

TECHNIQUES

Under inert collagen membrane (ACI)

On inert collagen membrane (MACI)

Harvest 200-300mg full thickness cartilage from trochlea (non load bearing)

Cells grown on monolayer with patients serum

No cells x 20-30

ACIMACI GENERIC METHOD

ACI METHOD

TREATMENT WITH CARTICEL

Uses your own cartilage cells (chondrocytes) to repair the articular cartilage damage in your knee When implanted into a cartilage injury your own cells can form new cartilage this new cartilage is very similar to your original cartilage The CARTICEL implantation procedure is called Autologous Chondrocyte Implantation or ACI It is a two-step process

Knee Cartilage Arthroscopy and BiopsyDuring an arthroscopic procedure surgeon assesses the extent of cartilage damage amp pt as a candidate for CARTICEL implantation

ldquoBiopsyrdquo of healthy tissue about the size of a pencil eraser ie about 200 -300 mg

From outer edge of sup Med or lat Femoral condyle or inner edge of lat Femoral condyle at the intercondylar notch

This sample is sent to product labs

Step 1 Biopsy

Biopsy can be stored for up to two years so you can schedule your surgery at your convenience

When you are ready your cells are cultured over three to five weeks they increase to approx 12 million cells in a vial containing 03 ndash 04 cc of medium Every step of the manufacturing process is monitored to ensure high quality and safety

CARTICEL MANUFACTURING AND DELIVERY

STEP 2 IMPLANTATION

Cartilage Injury CleanedDuring this second stage arthrotomy done to expose knee and any dead or damaged tissue from the injury removed with curette leaving only healthy tissue

Biomachenical allignment procedures if required should be done in conjunction with implantation

CARTICEL IMPLANTATION

PERIOSTEAL PATCH

surgeon takes a small piece of tissue from your shin bone and sews it securely over the injury

CARTICEL Implantation surgeon injects CARTICEL under the patch

When CARTICEL is surgically implanted into a cartilage injury it can grow and form new hyaline-like cartilage with properties similar to those of the original cartilage

Repairing the injury helps to reduce pain and improve movement and function

ACI STEPS summarised

MACI METHOD

Cultured chondrocytes seeded in bilayered typeIIII collagen membrane

Implanted using fibrin glue

Matrix remodelled in months replaced by extracellular matrix regenerate

The overall failure rate is at present quoted as being 10 The two most common complications include bullloosening of the transplant tissue bullformation of fibrous tissue at the repair site and adhesions with return of pain and locking Neither of these complications usually leaves the patient in a worse condition than hisher pre-transplantation state

Other adverse events include bullpost-op haematoma (big blood clot)bullhypertrophic synovitis (angry knee) and superficial wound infection

COMPLICATIONS

IMPROVEMENTS IN CLINICAL OUTCOME

ASSESMENT OF TECHNIQUE

FOLLOW UP RESULTS

ONE YEAR ASSESSMENT

Radiographs Alignment Bone quality

MRI Healing

cartilage Graft failure

Arthroscopy + probe Graft integrity Pressure biopsy

FOLLOW UP BIOPSY

FOLLOW UP MRI

Final appearance of theperiosteum sutured overfemoral condyle defect Thecartilage cells have beeninjected under the flap and thefinal suture placed to close thecover and provide a watertightseal

FOLLOW UP ARTHROSCOPIC

Arthroscopic appearance of thesame area 12 months afterCarticeltrade implantation Thedefect is no longer visible andthere is now hyaline cartilage(biopsy proven) filling theoriginal defect site

REHABILITATION GUIDELINES

Immobilization first 12-24 hours

(CPM) after 12-24 hours for about 4 weeks

Complete joint loading from about 5th week trochleapatellafrom about 8th week condyle Back to sports Low impact rarr within 6 monthsRepeated impact rarr from 8th monthHigh impact rarr from 10-12th month

ACI REHABILITATION

Weight bearingIt is recommended to keep you in non-weight bearing until the second week after surgery (ACI) You can increase the weight bearing gradually and you may be able to sustain your full weight bearing after 6 to 12 weeks from surgery

Range of motionRecovery on your ROM (Range of Motion) is gradually increased with a continuous passive motion (CPM) machine and may be completed to 140 degrees of ROM at 6 weeks to 12 weeks after surgery

ACI REHABILITATIONIndoor exerciseYou can strenghthen your muscles surrounding the knee joint with a four point exercise as well as isometric hamstring and squatting exercises from 4 weeks to 6 weeks after surgeryYou may start performing stationary bike activity without resistance and increase the resistance gradually

Outdoor exerciseAt 13 weeks after surgery you can start walking lightly and at 10 months after surgery you can perform jogging and then you may enjoy intensity exercise like playing tennis or volleyball from 18 months after surgery

Rehabilitation Goals at 12 weeks after ACIFull ROM (Range of Motion) Minimal edema level Minimal occasional pain Pain free tolerance to transitional phase exercise with adequate stability and motor control

COMPARISON WITH OTHER METHODS OF TREATMENTS

Autologous Chondrocyte Implantation Aims to increase the best condition for cartilage defectAdvantagesbullHyaline cartilage is formed bullPermanent reconstructed cartilage tissue bullMost valuable treatment

bullWith Fourth Generation ACI Use of cell ndash gel mixture (collagen hyaluronic acid and fibrin) has fast gelling properties (1 ndash 5 min) upon transplantation bullNo membrane or periosteal patch bullMinimal surgical exposure and reduced surgery time bullCorrects evenly irregular defect shapes bullApplicable to larger defects

COMPARISON WITH OTHER METHODS OF TREATMENTShelliphelliphellip

Abrasion arthroplastyAims to decrease the inflammation of the jointDisadvantagesbullRemoves many cartilage fragments from the jointbullSymptoms reoccur within one year

Drilling and MicrofractureAims to generate a healing responseDisadvantagesbullThe healing response in inadequate bullNo hyaline cartilage is formed but rather fibrocartilage bullHas a limited lifespan of approximately one year bullRapid deterioration after such procedures can be expected

COMPARISON WITH OTHER METHODS OF TREATMENTShelliphelliphellip

Perichondral ResurfacingDisadvantagesbullIsolated cartilage defects are often too large to be covered byh perichondrum bullLong term follow-up of such procedures indicate that the implants undergo endochondral ossification

Synthetic Materials (ie Carbon Fiber Mesh)Disadvantagesbull It often results in fibrous tissue formation bullNot adequate biomechanically bullOften the cause for synovitis in the joints

Osteocartiloginous GraftsAims to reconstruct jointsDisadvantagesbullUnless fresh cartilage is transplanted the cartilage is dead bullFresh grafts are not commonly used as they inevitably carry a risk of disease transmission bullCyropreserved grafts can survive for many years but ultimately deteriorate

Results of the Carticeltrade procedure have been encouraging although it is not always successful An analysis was done of the US and Swedish registry of 153 consecutive patients undergoing this procedure with follow-up from 1 week to 94 months The following results were obtainedbull Patients with clinical improvement 85bull Good or Excellent results 42 bull Good or Excellent results at 2 yearspersisting at 5 years post-op 97

Thus a total of 85 of patients showed some or complete improvement with theimplantation technique The Carticel procedure demonstrated good durability at 5-10 years out

CONCLUSIONS

CONCLUSIONS ACI Vs MACI No current evidence to justify aggressive treatment of

asymptomatic lesions with ACIMACI

Patients with full thickness symptomatic defects do poorly if left untreated

ACI and MACI lead to significant improvement in objective and patient reported clinical outcome scores for up to ten years(even among those with previous failed marrow stimulation techniques)

MACI has a superior rate of clinical improvement in comparison to ACI

Repair tissue may remodel and improve in quality with time

ACI and MACI comparable at 6 years

RECENT ADVANCESHYAFF 3D MATRIX

HYAFF biomaterialscontain high quantities ofderivatized HA

HA-richchondrocyte compatibleembryonic-like mileuconductive to regenerativehealing patterns

bull Non woven felt 2 mm thick fiber diameter 10 micronsbull Chondrocytes are isolated and passaged in culture on plasticdishes up to 3 weeksbull Cells are seeded for 2 weeks on HYAFF scaffold at a density of1 x 106 cm2 resulting in a total of 4 x 106 cm2 seeded cells pergraft

HYAFF-BASED SCAFFOLD

CHONDRONtrade

Uses a cell ndash gel mixture (includes collagen hyaluronic acid and fibrin) that has fast gelling properties (1 ndash 5 min) upon transplantation

This cell and gel mixture enable even cell distribution three-dimensionally moldable to fit irregular defect shape and applicable to a larger defectThus there is minimal surgical exposure and reduced surgery time

(three-dimensional reconstruction of a chondron from the growth plate of the murine long bone the model was generated from multiple sections imaged in an electron microscope plasma membranes are coloured green and internal organelles are visible within the top cell)

RECOVERY TO

HEALTHY ACTIVE LIFE

THANK YOU

• journal club (22-10-09)
• topic autologus chondrocyte implantation
• THE ROLE OF AUTOLOGOUS CHONDROCYTE IMPLANTATION (ACI) IN THE TR
• Slide 4
• AUTOLOGOUS CHONDROCYTE GRAFTS MULTICENTRIC TRIAL WITH 28 KNEE
• Slide 6
• Slide 7
• Articular Cartilage
• Hyaline Cartilage Structure 1048715The ldquostuffrdquo of cartilage
• Slide 11
• Cartilage Injury Occurs in Many Forms
• Articular Cartilage Defects a treatment challenge
• AND WHAT IS IN OUR BASKET
• SO IT LED US TO SEARCH OF MORE PROMISING OPTION
• Autologous Chondrocyte Implantation (ACI) BACKGROUND
• Identifying a Carticelreg Patient
• Identifying a Carticelreg Patienthelliphellip
• Pre-requisite for surgery
• Autologous Chondrocyte Implantation (ACI)
• Techniques
• ACIMACI Generic Method
• Slide 23
• Treatment with CARTICEL
• CARTICEL Manufacturing and Delivery
• Step 2 Implantation
• CARTICEL Implantation
• Periosteal Patch
• Slide 29
• Slide 30
• Aci steps summarised
• Slide 32
• Complications
• Slide 34
• Slide 35
• FOLLOW UP Biopsy
• FOLLOW UP MRI
• FOLLOW UP ARTHROSCOPIC
• Rehabilitation guidelines
• ACI Rehabilitation
• ACI Rehabilitation (2)
• COMPARISON WITH OTHER METHODS OF TREATMENTS
• COMPARISON WITH OTHER METHODS OF TREATMENTShelliphelliphellip
• COMPARISON WITH OTHER METHODS OF TREATMENTShelliphelliphellip (2)
• CONCLUSIONS
• Slide 46
• Recent advancesHYAFF 3D matrix
• HYAFF-based Scaffold
• CHONDRONtrade
• RECOVERY TO
• Slide 51

ARTICULAR CARTILAGE

Chondrocytes (cartilage cells) embedded in a Highly specialised ECM

Gives elasticityProvides resistance to

tensilecompressive and shear forces

Acts as a smooth efficient surface for motion

HYALINE CARTILAGE STRUCTURE1048715THE ldquoSTUFFrdquo OF CARTILAGE

Functions of the Articular Cartilage ndash Distribute loadndash Absorb shock

CHONDRAL INJURIES

Deficient in type II collagen

Lower load bearing capacity

INEVITABLE lsquoSHORT TERMrsquo RECOVERY

Commonly these injuries heal by scar tissue formation

PREVALENCE AND INCIDENCE

993 consecutive arthroscopies ndash 66 articular cartilage pathology 11 full thickness localised lesions suitable for repair procedures

Aroen A Loken S Heir S et al Am J Sports Med 2004 32 211-15

31000 arthroscopic procedures ndash 63 articular cartilage lesions

Curl WW Krome J Gordon ES et al Arthroscopy 1997 13 456-60

1000 consecutive arthroscopies ndash 19 localised chondralosteochondral lesionsHjelle K et al Arthroscopy 2002 18 730-4

CARTILAGE INJURY OCCURS IN MANY FORMS

Trauma sports or work related

Chronic instability long term effects ACL and othermeniscal deficiency

Mal-aligned joint - deformityvarus Valgus

Osteochondritis Dissecans [OCD]

Genetic pre-disposition earlyarthritis

bull Most full-thickness defects are symptomaticndash Pain swelling locking catching grinding

bull Left untreatedmay progress to significant articular defects

ARTICULAR CARTILAGE DEFECTS A TREATMENT CHALLENGE

bullMay lead to debilitatingosteoarthritis

Arthroscopic Debridement

Arthroscopic lavage

Subchondral drilling

Microfracture MARROW STIMULATION TECHNIQUES Abrasion arthroplasty -to induce the growth of fibrocartilage into the chondral defect (This fibrocartilage does not withstand shock or shearing force as well as the original hyaline cartilage and may deteriorate over time)

AND WHAT IS IN OUR BASKET

AUTOLOGUS CHONDROCYTE IMPLANTATION

SO IT LED US TO SEARCH OF MORE PROMISING OPTION

JBJS [Am] 1987 Peterson et al Gothenburgndash first application of cell engineering in orthopaedics

NEJM 1994 Brittberg et al Swedenndash successfuly regenerated hyaline-like cartilage in isolated chondral defects

AUTOLOGOUS CHONDROCYTE IMPLANTATION (ACI) BACKGROUND

IDENTIFYING A CARTICELreg PATIENT

Patient FactorsYounger patients ndash lt age 45 - 50 (avg ~ 35 yo)

Significant impairment-Compromised daily livingactivities -Refractory to treatment

Obesity

Demanding Physical activities

Willing amp capable of rehabilitation program

IDENTIFYING A CARTICELreg PATIENThelliphellip

Joint FactorsSymptomatic cartilage defects -Moderate to large (gt 2cm2 d= 16) -On the distal femur (mfc lfc trochlea) -Average defect size gt 4 cm2

-Either chondral or osteochondral

Relatively healthy joint ndash -No arthritis

Co-morbidities(meniscal tear

instability or malalignment) must be corrected prior or concurrent to implantation

Pre-requisite for surgery

Not recommended for patients who have

Appropriate biomachenical alignment

Ligamentous stabilty

Range of motion

an unstable knee

patients sensitive to materials of bovine origins

allergic to the antibiotic gentamicin

in children

yet in any joint other than the knee

AUTOLOGOUS CHONDROCYTEIMPLANTATION (ACI)

StrengthsCan produce hyaline-like cartilageCan fill defects regardless of size with functional repair tissueModerate to large defects that have failed previous interventionRepair tissue which matures rather than deteriorates over timeExpected outcomeReturn to previous level of functioning

ldquoBiological Joint replacementrdquo

LimitationsMore invasiveExpenseLonger recovery

A ACI ndash Periosteum (cells under periosteum)

B ACI ndash Chondrogide (cells under membrane)

C MACI ndash Matrix Induced ACI (cells on membrane)

Chondrogide Membrane Porcine type IIII Inert Seal Resorbs in 3-4 months

ACI MACI

TECHNIQUES

Under inert collagen membrane (ACI)

On inert collagen membrane (MACI)

Harvest 200-300mg full thickness cartilage from trochlea (non load bearing)

Cells grown on monolayer with patients serum

No cells x 20-30

ACIMACI GENERIC METHOD

ACI METHOD

TREATMENT WITH CARTICEL

Uses your own cartilage cells (chondrocytes) to repair the articular cartilage damage in your knee When implanted into a cartilage injury your own cells can form new cartilage this new cartilage is very similar to your original cartilage The CARTICEL implantation procedure is called Autologous Chondrocyte Implantation or ACI It is a two-step process

Knee Cartilage Arthroscopy and BiopsyDuring an arthroscopic procedure surgeon assesses the extent of cartilage damage amp pt as a candidate for CARTICEL implantation

ldquoBiopsyrdquo of healthy tissue about the size of a pencil eraser ie about 200 -300 mg

From outer edge of sup Med or lat Femoral condyle or inner edge of lat Femoral condyle at the intercondylar notch

This sample is sent to product labs

Step 1 Biopsy

Biopsy can be stored for up to two years so you can schedule your surgery at your convenience

When you are ready your cells are cultured over three to five weeks they increase to approx 12 million cells in a vial containing 03 ndash 04 cc of medium Every step of the manufacturing process is monitored to ensure high quality and safety

CARTICEL MANUFACTURING AND DELIVERY

STEP 2 IMPLANTATION

Cartilage Injury CleanedDuring this second stage arthrotomy done to expose knee and any dead or damaged tissue from the injury removed with curette leaving only healthy tissue

Biomachenical allignment procedures if required should be done in conjunction with implantation

CARTICEL IMPLANTATION

PERIOSTEAL PATCH

surgeon takes a small piece of tissue from your shin bone and sews it securely over the injury

CARTICEL Implantation surgeon injects CARTICEL under the patch

When CARTICEL is surgically implanted into a cartilage injury it can grow and form new hyaline-like cartilage with properties similar to those of the original cartilage

Repairing the injury helps to reduce pain and improve movement and function

ACI STEPS summarised

MACI METHOD

Cultured chondrocytes seeded in bilayered typeIIII collagen membrane

Implanted using fibrin glue

Matrix remodelled in months replaced by extracellular matrix regenerate

The overall failure rate is at present quoted as being 10 The two most common complications include bullloosening of the transplant tissue bullformation of fibrous tissue at the repair site and adhesions with return of pain and locking Neither of these complications usually leaves the patient in a worse condition than hisher pre-transplantation state

Other adverse events include bullpost-op haematoma (big blood clot)bullhypertrophic synovitis (angry knee) and superficial wound infection

COMPLICATIONS

IMPROVEMENTS IN CLINICAL OUTCOME

ASSESMENT OF TECHNIQUE

FOLLOW UP RESULTS

ONE YEAR ASSESSMENT

Radiographs Alignment Bone quality

MRI Healing

cartilage Graft failure

Arthroscopy + probe Graft integrity Pressure biopsy

FOLLOW UP BIOPSY

FOLLOW UP MRI

Final appearance of theperiosteum sutured overfemoral condyle defect Thecartilage cells have beeninjected under the flap and thefinal suture placed to close thecover and provide a watertightseal

FOLLOW UP ARTHROSCOPIC

Arthroscopic appearance of thesame area 12 months afterCarticeltrade implantation Thedefect is no longer visible andthere is now hyaline cartilage(biopsy proven) filling theoriginal defect site

REHABILITATION GUIDELINES

Immobilization first 12-24 hours

(CPM) after 12-24 hours for about 4 weeks

Complete joint loading from about 5th week trochleapatellafrom about 8th week condyle Back to sports Low impact rarr within 6 monthsRepeated impact rarr from 8th monthHigh impact rarr from 10-12th month

ACI REHABILITATION

Weight bearingIt is recommended to keep you in non-weight bearing until the second week after surgery (ACI) You can increase the weight bearing gradually and you may be able to sustain your full weight bearing after 6 to 12 weeks from surgery

Range of motionRecovery on your ROM (Range of Motion) is gradually increased with a continuous passive motion (CPM) machine and may be completed to 140 degrees of ROM at 6 weeks to 12 weeks after surgery

ACI REHABILITATIONIndoor exerciseYou can strenghthen your muscles surrounding the knee joint with a four point exercise as well as isometric hamstring and squatting exercises from 4 weeks to 6 weeks after surgeryYou may start performing stationary bike activity without resistance and increase the resistance gradually

Outdoor exerciseAt 13 weeks after surgery you can start walking lightly and at 10 months after surgery you can perform jogging and then you may enjoy intensity exercise like playing tennis or volleyball from 18 months after surgery

Rehabilitation Goals at 12 weeks after ACIFull ROM (Range of Motion) Minimal edema level Minimal occasional pain Pain free tolerance to transitional phase exercise with adequate stability and motor control

COMPARISON WITH OTHER METHODS OF TREATMENTS

Autologous Chondrocyte Implantation Aims to increase the best condition for cartilage defectAdvantagesbullHyaline cartilage is formed bullPermanent reconstructed cartilage tissue bullMost valuable treatment

bullWith Fourth Generation ACI Use of cell ndash gel mixture (collagen hyaluronic acid and fibrin) has fast gelling properties (1 ndash 5 min) upon transplantation bullNo membrane or periosteal patch bullMinimal surgical exposure and reduced surgery time bullCorrects evenly irregular defect shapes bullApplicable to larger defects

COMPARISON WITH OTHER METHODS OF TREATMENTShelliphelliphellip

Abrasion arthroplastyAims to decrease the inflammation of the jointDisadvantagesbullRemoves many cartilage fragments from the jointbullSymptoms reoccur within one year

Drilling and MicrofractureAims to generate a healing responseDisadvantagesbullThe healing response in inadequate bullNo hyaline cartilage is formed but rather fibrocartilage bullHas a limited lifespan of approximately one year bullRapid deterioration after such procedures can be expected

COMPARISON WITH OTHER METHODS OF TREATMENTShelliphelliphellip

Perichondral ResurfacingDisadvantagesbullIsolated cartilage defects are often too large to be covered byh perichondrum bullLong term follow-up of such procedures indicate that the implants undergo endochondral ossification

Synthetic Materials (ie Carbon Fiber Mesh)Disadvantagesbull It often results in fibrous tissue formation bullNot adequate biomechanically bullOften the cause for synovitis in the joints

Osteocartiloginous GraftsAims to reconstruct jointsDisadvantagesbullUnless fresh cartilage is transplanted the cartilage is dead bullFresh grafts are not commonly used as they inevitably carry a risk of disease transmission bullCyropreserved grafts can survive for many years but ultimately deteriorate

Results of the Carticeltrade procedure have been encouraging although it is not always successful An analysis was done of the US and Swedish registry of 153 consecutive patients undergoing this procedure with follow-up from 1 week to 94 months The following results were obtainedbull Patients with clinical improvement 85bull Good or Excellent results 42 bull Good or Excellent results at 2 yearspersisting at 5 years post-op 97

Thus a total of 85 of patients showed some or complete improvement with theimplantation technique The Carticel procedure demonstrated good durability at 5-10 years out

CONCLUSIONS

CONCLUSIONS ACI Vs MACI No current evidence to justify aggressive treatment of

asymptomatic lesions with ACIMACI

Patients with full thickness symptomatic defects do poorly if left untreated

ACI and MACI lead to significant improvement in objective and patient reported clinical outcome scores for up to ten years(even among those with previous failed marrow stimulation techniques)

MACI has a superior rate of clinical improvement in comparison to ACI

Repair tissue may remodel and improve in quality with time

ACI and MACI comparable at 6 years

RECENT ADVANCESHYAFF 3D MATRIX

HYAFF biomaterialscontain high quantities ofderivatized HA

HA-richchondrocyte compatibleembryonic-like mileuconductive to regenerativehealing patterns

bull Non woven felt 2 mm thick fiber diameter 10 micronsbull Chondrocytes are isolated and passaged in culture on plasticdishes up to 3 weeksbull Cells are seeded for 2 weeks on HYAFF scaffold at a density of1 x 106 cm2 resulting in a total of 4 x 106 cm2 seeded cells pergraft

HYAFF-BASED SCAFFOLD

CHONDRONtrade

Uses a cell ndash gel mixture (includes collagen hyaluronic acid and fibrin) that has fast gelling properties (1 ndash 5 min) upon transplantation

This cell and gel mixture enable even cell distribution three-dimensionally moldable to fit irregular defect shape and applicable to a larger defectThus there is minimal surgical exposure and reduced surgery time

(three-dimensional reconstruction of a chondron from the growth plate of the murine long bone the model was generated from multiple sections imaged in an electron microscope plasma membranes are coloured green and internal organelles are visible within the top cell)

RECOVERY TO

HEALTHY ACTIVE LIFE

THANK YOU

• journal club (22-10-09)
• topic autologus chondrocyte implantation
• THE ROLE OF AUTOLOGOUS CHONDROCYTE IMPLANTATION (ACI) IN THE TR
• Slide 4
• AUTOLOGOUS CHONDROCYTE GRAFTS MULTICENTRIC TRIAL WITH 28 KNEE
• Slide 6
• Slide 7
• Articular Cartilage
• Hyaline Cartilage Structure 1048715The ldquostuffrdquo of cartilage
• Slide 11
• Cartilage Injury Occurs in Many Forms
• Articular Cartilage Defects a treatment challenge
• AND WHAT IS IN OUR BASKET
• SO IT LED US TO SEARCH OF MORE PROMISING OPTION
• Autologous Chondrocyte Implantation (ACI) BACKGROUND
• Identifying a Carticelreg Patient
• Identifying a Carticelreg Patienthelliphellip
• Pre-requisite for surgery
• Autologous Chondrocyte Implantation (ACI)
• Techniques
• ACIMACI Generic Method
• Slide 23
• Treatment with CARTICEL
• CARTICEL Manufacturing and Delivery
• Step 2 Implantation
• CARTICEL Implantation
• Periosteal Patch
• Slide 29
• Slide 30
• Aci steps summarised
• Slide 32
• Complications
• Slide 34
• Slide 35
• FOLLOW UP Biopsy
• FOLLOW UP MRI
• FOLLOW UP ARTHROSCOPIC
• Rehabilitation guidelines
• ACI Rehabilitation
• ACI Rehabilitation (2)
• COMPARISON WITH OTHER METHODS OF TREATMENTS
• COMPARISON WITH OTHER METHODS OF TREATMENTShelliphelliphellip
• COMPARISON WITH OTHER METHODS OF TREATMENTShelliphelliphellip (2)
• CONCLUSIONS
• Slide 46
• Recent advancesHYAFF 3D matrix
• HYAFF-based Scaffold
• CHONDRONtrade
• RECOVERY TO
• Slide 51

HYALINE CARTILAGE STRUCTURE1048715THE ldquoSTUFFrdquo OF CARTILAGE

Functions of the Articular Cartilage ndash Distribute loadndash Absorb shock

CHONDRAL INJURIES

Deficient in type II collagen

Lower load bearing capacity

INEVITABLE lsquoSHORT TERMrsquo RECOVERY

Commonly these injuries heal by scar tissue formation

PREVALENCE AND INCIDENCE

993 consecutive arthroscopies ndash 66 articular cartilage pathology 11 full thickness localised lesions suitable for repair procedures

Aroen A Loken S Heir S et al Am J Sports Med 2004 32 211-15

31000 arthroscopic procedures ndash 63 articular cartilage lesions

Curl WW Krome J Gordon ES et al Arthroscopy 1997 13 456-60

1000 consecutive arthroscopies ndash 19 localised chondralosteochondral lesionsHjelle K et al Arthroscopy 2002 18 730-4

CARTILAGE INJURY OCCURS IN MANY FORMS

Trauma sports or work related

Chronic instability long term effects ACL and othermeniscal deficiency

Mal-aligned joint - deformityvarus Valgus

Osteochondritis Dissecans [OCD]

Genetic pre-disposition earlyarthritis

bull Most full-thickness defects are symptomaticndash Pain swelling locking catching grinding

bull Left untreatedmay progress to significant articular defects

ARTICULAR CARTILAGE DEFECTS A TREATMENT CHALLENGE

bullMay lead to debilitatingosteoarthritis

Arthroscopic Debridement

Arthroscopic lavage

Subchondral drilling

Microfracture MARROW STIMULATION TECHNIQUES Abrasion arthroplasty -to induce the growth of fibrocartilage into the chondral defect (This fibrocartilage does not withstand shock or shearing force as well as the original hyaline cartilage and may deteriorate over time)

AND WHAT IS IN OUR BASKET

AUTOLOGUS CHONDROCYTE IMPLANTATION

SO IT LED US TO SEARCH OF MORE PROMISING OPTION

JBJS [Am] 1987 Peterson et al Gothenburgndash first application of cell engineering in orthopaedics

NEJM 1994 Brittberg et al Swedenndash successfuly regenerated hyaline-like cartilage in isolated chondral defects

AUTOLOGOUS CHONDROCYTE IMPLANTATION (ACI) BACKGROUND

IDENTIFYING A CARTICELreg PATIENT

Patient FactorsYounger patients ndash lt age 45 - 50 (avg ~ 35 yo)

Significant impairment-Compromised daily livingactivities -Refractory to treatment

Obesity

Demanding Physical activities

Willing amp capable of rehabilitation program

IDENTIFYING A CARTICELreg PATIENThelliphellip

Joint FactorsSymptomatic cartilage defects -Moderate to large (gt 2cm2 d= 16) -On the distal femur (mfc lfc trochlea) -Average defect size gt 4 cm2

-Either chondral or osteochondral

Relatively healthy joint ndash -No arthritis

Co-morbidities(meniscal tear

instability or malalignment) must be corrected prior or concurrent to implantation

Pre-requisite for surgery

Not recommended for patients who have

Appropriate biomachenical alignment

Ligamentous stabilty

Range of motion

an unstable knee

patients sensitive to materials of bovine origins

allergic to the antibiotic gentamicin

in children

yet in any joint other than the knee

AUTOLOGOUS CHONDROCYTEIMPLANTATION (ACI)

StrengthsCan produce hyaline-like cartilageCan fill defects regardless of size with functional repair tissueModerate to large defects that have failed previous interventionRepair tissue which matures rather than deteriorates over timeExpected outcomeReturn to previous level of functioning

ldquoBiological Joint replacementrdquo

LimitationsMore invasiveExpenseLonger recovery

A ACI ndash Periosteum (cells under periosteum)

B ACI ndash Chondrogide (cells under membrane)

C MACI ndash Matrix Induced ACI (cells on membrane)

Chondrogide Membrane Porcine type IIII Inert Seal Resorbs in 3-4 months

ACI MACI

TECHNIQUES

Under inert collagen membrane (ACI)

On inert collagen membrane (MACI)

Harvest 200-300mg full thickness cartilage from trochlea (non load bearing)

Cells grown on monolayer with patients serum

No cells x 20-30

ACIMACI GENERIC METHOD

ACI METHOD

TREATMENT WITH CARTICEL

Uses your own cartilage cells (chondrocytes) to repair the articular cartilage damage in your knee When implanted into a cartilage injury your own cells can form new cartilage this new cartilage is very similar to your original cartilage The CARTICEL implantation procedure is called Autologous Chondrocyte Implantation or ACI It is a two-step process

Knee Cartilage Arthroscopy and BiopsyDuring an arthroscopic procedure surgeon assesses the extent of cartilage damage amp pt as a candidate for CARTICEL implantation

ldquoBiopsyrdquo of healthy tissue about the size of a pencil eraser ie about 200 -300 mg

From outer edge of sup Med or lat Femoral condyle or inner edge of lat Femoral condyle at the intercondylar notch

This sample is sent to product labs

Step 1 Biopsy

Biopsy can be stored for up to two years so you can schedule your surgery at your convenience

When you are ready your cells are cultured over three to five weeks they increase to approx 12 million cells in a vial containing 03 ndash 04 cc of medium Every step of the manufacturing process is monitored to ensure high quality and safety

CARTICEL MANUFACTURING AND DELIVERY

STEP 2 IMPLANTATION

Cartilage Injury CleanedDuring this second stage arthrotomy done to expose knee and any dead or damaged tissue from the injury removed with curette leaving only healthy tissue

Biomachenical allignment procedures if required should be done in conjunction with implantation

CARTICEL IMPLANTATION

PERIOSTEAL PATCH

surgeon takes a small piece of tissue from your shin bone and sews it securely over the injury

CARTICEL Implantation surgeon injects CARTICEL under the patch

When CARTICEL is surgically implanted into a cartilage injury it can grow and form new hyaline-like cartilage with properties similar to those of the original cartilage

Repairing the injury helps to reduce pain and improve movement and function

ACI STEPS summarised

MACI METHOD

Cultured chondrocytes seeded in bilayered typeIIII collagen membrane

Implanted using fibrin glue

Matrix remodelled in months replaced by extracellular matrix regenerate

The overall failure rate is at present quoted as being 10 The two most common complications include bullloosening of the transplant tissue bullformation of fibrous tissue at the repair site and adhesions with return of pain and locking Neither of these complications usually leaves the patient in a worse condition than hisher pre-transplantation state

Other adverse events include bullpost-op haematoma (big blood clot)bullhypertrophic synovitis (angry knee) and superficial wound infection

COMPLICATIONS

IMPROVEMENTS IN CLINICAL OUTCOME

ASSESMENT OF TECHNIQUE

FOLLOW UP RESULTS

ONE YEAR ASSESSMENT

Radiographs Alignment Bone quality

MRI Healing

cartilage Graft failure

Arthroscopy + probe Graft integrity Pressure biopsy

FOLLOW UP BIOPSY

FOLLOW UP MRI

Final appearance of theperiosteum sutured overfemoral condyle defect Thecartilage cells have beeninjected under the flap and thefinal suture placed to close thecover and provide a watertightseal

FOLLOW UP ARTHROSCOPIC

Arthroscopic appearance of thesame area 12 months afterCarticeltrade implantation Thedefect is no longer visible andthere is now hyaline cartilage(biopsy proven) filling theoriginal defect site

REHABILITATION GUIDELINES

Immobilization first 12-24 hours

(CPM) after 12-24 hours for about 4 weeks

Complete joint loading from about 5th week trochleapatellafrom about 8th week condyle Back to sports Low impact rarr within 6 monthsRepeated impact rarr from 8th monthHigh impact rarr from 10-12th month

ACI REHABILITATION

Weight bearingIt is recommended to keep you in non-weight bearing until the second week after surgery (ACI) You can increase the weight bearing gradually and you may be able to sustain your full weight bearing after 6 to 12 weeks from surgery

Range of motionRecovery on your ROM (Range of Motion) is gradually increased with a continuous passive motion (CPM) machine and may be completed to 140 degrees of ROM at 6 weeks to 12 weeks after surgery

ACI REHABILITATIONIndoor exerciseYou can strenghthen your muscles surrounding the knee joint with a four point exercise as well as isometric hamstring and squatting exercises from 4 weeks to 6 weeks after surgeryYou may start performing stationary bike activity without resistance and increase the resistance gradually

Outdoor exerciseAt 13 weeks after surgery you can start walking lightly and at 10 months after surgery you can perform jogging and then you may enjoy intensity exercise like playing tennis or volleyball from 18 months after surgery

Rehabilitation Goals at 12 weeks after ACIFull ROM (Range of Motion) Minimal edema level Minimal occasional pain Pain free tolerance to transitional phase exercise with adequate stability and motor control

COMPARISON WITH OTHER METHODS OF TREATMENTS

Autologous Chondrocyte Implantation Aims to increase the best condition for cartilage defectAdvantagesbullHyaline cartilage is formed bullPermanent reconstructed cartilage tissue bullMost valuable treatment

bullWith Fourth Generation ACI Use of cell ndash gel mixture (collagen hyaluronic acid and fibrin) has fast gelling properties (1 ndash 5 min) upon transplantation bullNo membrane or periosteal patch bullMinimal surgical exposure and reduced surgery time bullCorrects evenly irregular defect shapes bullApplicable to larger defects

COMPARISON WITH OTHER METHODS OF TREATMENTShelliphelliphellip

Abrasion arthroplastyAims to decrease the inflammation of the jointDisadvantagesbullRemoves many cartilage fragments from the jointbullSymptoms reoccur within one year

Drilling and MicrofractureAims to generate a healing responseDisadvantagesbullThe healing response in inadequate bullNo hyaline cartilage is formed but rather fibrocartilage bullHas a limited lifespan of approximately one year bullRapid deterioration after such procedures can be expected

COMPARISON WITH OTHER METHODS OF TREATMENTShelliphelliphellip

Perichondral ResurfacingDisadvantagesbullIsolated cartilage defects are often too large to be covered byh perichondrum bullLong term follow-up of such procedures indicate that the implants undergo endochondral ossification

Synthetic Materials (ie Carbon Fiber Mesh)Disadvantagesbull It often results in fibrous tissue formation bullNot adequate biomechanically bullOften the cause for synovitis in the joints

Osteocartiloginous GraftsAims to reconstruct jointsDisadvantagesbullUnless fresh cartilage is transplanted the cartilage is dead bullFresh grafts are not commonly used as they inevitably carry a risk of disease transmission bullCyropreserved grafts can survive for many years but ultimately deteriorate

Results of the Carticeltrade procedure have been encouraging although it is not always successful An analysis was done of the US and Swedish registry of 153 consecutive patients undergoing this procedure with follow-up from 1 week to 94 months The following results were obtainedbull Patients with clinical improvement 85bull Good or Excellent results 42 bull Good or Excellent results at 2 yearspersisting at 5 years post-op 97

Thus a total of 85 of patients showed some or complete improvement with theimplantation technique The Carticel procedure demonstrated good durability at 5-10 years out

CONCLUSIONS

CONCLUSIONS ACI Vs MACI No current evidence to justify aggressive treatment of

asymptomatic lesions with ACIMACI

Patients with full thickness symptomatic defects do poorly if left untreated

ACI and MACI lead to significant improvement in objective and patient reported clinical outcome scores for up to ten years(even among those with previous failed marrow stimulation techniques)

MACI has a superior rate of clinical improvement in comparison to ACI

Repair tissue may remodel and improve in quality with time

ACI and MACI comparable at 6 years

RECENT ADVANCESHYAFF 3D MATRIX

HYAFF biomaterialscontain high quantities ofderivatized HA

HA-richchondrocyte compatibleembryonic-like mileuconductive to regenerativehealing patterns

bull Non woven felt 2 mm thick fiber diameter 10 micronsbull Chondrocytes are isolated and passaged in culture on plasticdishes up to 3 weeksbull Cells are seeded for 2 weeks on HYAFF scaffold at a density of1 x 106 cm2 resulting in a total of 4 x 106 cm2 seeded cells pergraft

HYAFF-BASED SCAFFOLD

CHONDRONtrade

Uses a cell ndash gel mixture (includes collagen hyaluronic acid and fibrin) that has fast gelling properties (1 ndash 5 min) upon transplantation

This cell and gel mixture enable even cell distribution three-dimensionally moldable to fit irregular defect shape and applicable to a larger defectThus there is minimal surgical exposure and reduced surgery time

(three-dimensional reconstruction of a chondron from the growth plate of the murine long bone the model was generated from multiple sections imaged in an electron microscope plasma membranes are coloured green and internal organelles are visible within the top cell)

RECOVERY TO

HEALTHY ACTIVE LIFE

THANK YOU

• journal club (22-10-09)
• topic autologus chondrocyte implantation
• THE ROLE OF AUTOLOGOUS CHONDROCYTE IMPLANTATION (ACI) IN THE TR
• Slide 4
• AUTOLOGOUS CHONDROCYTE GRAFTS MULTICENTRIC TRIAL WITH 28 KNEE
• Slide 6
• Slide 7
• Articular Cartilage
• Hyaline Cartilage Structure 1048715The ldquostuffrdquo of cartilage
• Slide 11
• Cartilage Injury Occurs in Many Forms
• Articular Cartilage Defects a treatment challenge
• AND WHAT IS IN OUR BASKET
• SO IT LED US TO SEARCH OF MORE PROMISING OPTION
• Autologous Chondrocyte Implantation (ACI) BACKGROUND
• Identifying a Carticelreg Patient
• Identifying a Carticelreg Patienthelliphellip
• Pre-requisite for surgery
• Autologous Chondrocyte Implantation (ACI)
• Techniques
• ACIMACI Generic Method
• Slide 23
• Treatment with CARTICEL
• CARTICEL Manufacturing and Delivery
• Step 2 Implantation
• CARTICEL Implantation
• Periosteal Patch
• Slide 29
• Slide 30
• Aci steps summarised
• Slide 32
• Complications
• Slide 34
• Slide 35
• FOLLOW UP Biopsy
• FOLLOW UP MRI
• FOLLOW UP ARTHROSCOPIC
• Rehabilitation guidelines
• ACI Rehabilitation
• ACI Rehabilitation (2)
• COMPARISON WITH OTHER METHODS OF TREATMENTS
• COMPARISON WITH OTHER METHODS OF TREATMENTShelliphelliphellip
• COMPARISON WITH OTHER METHODS OF TREATMENTShelliphelliphellip (2)
• CONCLUSIONS
• Slide 46
• Recent advancesHYAFF 3D matrix
• HYAFF-based Scaffold
• CHONDRONtrade
• RECOVERY TO
• Slide 51

CHONDRAL INJURIES

Deficient in type II collagen

Lower load bearing capacity

INEVITABLE lsquoSHORT TERMrsquo RECOVERY

Commonly these injuries heal by scar tissue formation

PREVALENCE AND INCIDENCE

993 consecutive arthroscopies ndash 66 articular cartilage pathology 11 full thickness localised lesions suitable for repair procedures

Aroen A Loken S Heir S et al Am J Sports Med 2004 32 211-15

31000 arthroscopic procedures ndash 63 articular cartilage lesions

Curl WW Krome J Gordon ES et al Arthroscopy 1997 13 456-60

1000 consecutive arthroscopies ndash 19 localised chondralosteochondral lesionsHjelle K et al Arthroscopy 2002 18 730-4

CARTILAGE INJURY OCCURS IN MANY FORMS

Trauma sports or work related

Chronic instability long term effects ACL and othermeniscal deficiency

Mal-aligned joint - deformityvarus Valgus

Osteochondritis Dissecans [OCD]

Genetic pre-disposition earlyarthritis

bull Most full-thickness defects are symptomaticndash Pain swelling locking catching grinding

bull Left untreatedmay progress to significant articular defects

ARTICULAR CARTILAGE DEFECTS A TREATMENT CHALLENGE

bullMay lead to debilitatingosteoarthritis

Arthroscopic Debridement

Arthroscopic lavage

Subchondral drilling

Microfracture MARROW STIMULATION TECHNIQUES Abrasion arthroplasty -to induce the growth of fibrocartilage into the chondral defect (This fibrocartilage does not withstand shock or shearing force as well as the original hyaline cartilage and may deteriorate over time)

AND WHAT IS IN OUR BASKET

AUTOLOGUS CHONDROCYTE IMPLANTATION

SO IT LED US TO SEARCH OF MORE PROMISING OPTION

JBJS [Am] 1987 Peterson et al Gothenburgndash first application of cell engineering in orthopaedics

NEJM 1994 Brittberg et al Swedenndash successfuly regenerated hyaline-like cartilage in isolated chondral defects

AUTOLOGOUS CHONDROCYTE IMPLANTATION (ACI) BACKGROUND

IDENTIFYING A CARTICELreg PATIENT

Patient FactorsYounger patients ndash lt age 45 - 50 (avg ~ 35 yo)

Significant impairment-Compromised daily livingactivities -Refractory to treatment

Obesity

Demanding Physical activities

Willing amp capable of rehabilitation program

IDENTIFYING A CARTICELreg PATIENThelliphellip

Joint FactorsSymptomatic cartilage defects -Moderate to large (gt 2cm2 d= 16) -On the distal femur (mfc lfc trochlea) -Average defect size gt 4 cm2

-Either chondral or osteochondral

Relatively healthy joint ndash -No arthritis

Co-morbidities(meniscal tear

instability or malalignment) must be corrected prior or concurrent to implantation

Pre-requisite for surgery

Not recommended for patients who have

Appropriate biomachenical alignment

Ligamentous stabilty

Range of motion

an unstable knee

patients sensitive to materials of bovine origins

allergic to the antibiotic gentamicin

in children

yet in any joint other than the knee

AUTOLOGOUS CHONDROCYTEIMPLANTATION (ACI)

StrengthsCan produce hyaline-like cartilageCan fill defects regardless of size with functional repair tissueModerate to large defects that have failed previous interventionRepair tissue which matures rather than deteriorates over timeExpected outcomeReturn to previous level of functioning

ldquoBiological Joint replacementrdquo

LimitationsMore invasiveExpenseLonger recovery

A ACI ndash Periosteum (cells under periosteum)

B ACI ndash Chondrogide (cells under membrane)

C MACI ndash Matrix Induced ACI (cells on membrane)

Chondrogide Membrane Porcine type IIII Inert Seal Resorbs in 3-4 months

ACI MACI

TECHNIQUES

Under inert collagen membrane (ACI)

On inert collagen membrane (MACI)

Harvest 200-300mg full thickness cartilage from trochlea (non load bearing)

Cells grown on monolayer with patients serum

No cells x 20-30

ACIMACI GENERIC METHOD

ACI METHOD

TREATMENT WITH CARTICEL

Uses your own cartilage cells (chondrocytes) to repair the articular cartilage damage in your knee When implanted into a cartilage injury your own cells can form new cartilage this new cartilage is very similar to your original cartilage The CARTICEL implantation procedure is called Autologous Chondrocyte Implantation or ACI It is a two-step process

Knee Cartilage Arthroscopy and BiopsyDuring an arthroscopic procedure surgeon assesses the extent of cartilage damage amp pt as a candidate for CARTICEL implantation

ldquoBiopsyrdquo of healthy tissue about the size of a pencil eraser ie about 200 -300 mg

From outer edge of sup Med or lat Femoral condyle or inner edge of lat Femoral condyle at the intercondylar notch

This sample is sent to product labs

Step 1 Biopsy

Biopsy can be stored for up to two years so you can schedule your surgery at your convenience

When you are ready your cells are cultured over three to five weeks they increase to approx 12 million cells in a vial containing 03 ndash 04 cc of medium Every step of the manufacturing process is monitored to ensure high quality and safety

CARTICEL MANUFACTURING AND DELIVERY

STEP 2 IMPLANTATION

Cartilage Injury CleanedDuring this second stage arthrotomy done to expose knee and any dead or damaged tissue from the injury removed with curette leaving only healthy tissue

Biomachenical allignment procedures if required should be done in conjunction with implantation

CARTICEL IMPLANTATION

PERIOSTEAL PATCH

surgeon takes a small piece of tissue from your shin bone and sews it securely over the injury

CARTICEL Implantation surgeon injects CARTICEL under the patch

When CARTICEL is surgically implanted into a cartilage injury it can grow and form new hyaline-like cartilage with properties similar to those of the original cartilage

Repairing the injury helps to reduce pain and improve movement and function

ACI STEPS summarised

MACI METHOD

Cultured chondrocytes seeded in bilayered typeIIII collagen membrane

Implanted using fibrin glue

Matrix remodelled in months replaced by extracellular matrix regenerate

The overall failure rate is at present quoted as being 10 The two most common complications include bullloosening of the transplant tissue bullformation of fibrous tissue at the repair site and adhesions with return of pain and locking Neither of these complications usually leaves the patient in a worse condition than hisher pre-transplantation state

Other adverse events include bullpost-op haematoma (big blood clot)bullhypertrophic synovitis (angry knee) and superficial wound infection

COMPLICATIONS

IMPROVEMENTS IN CLINICAL OUTCOME

ASSESMENT OF TECHNIQUE

FOLLOW UP RESULTS

ONE YEAR ASSESSMENT

Radiographs Alignment Bone quality

MRI Healing

cartilage Graft failure

Arthroscopy + probe Graft integrity Pressure biopsy

FOLLOW UP BIOPSY

FOLLOW UP MRI

Final appearance of theperiosteum sutured overfemoral condyle defect Thecartilage cells have beeninjected under the flap and thefinal suture placed to close thecover and provide a watertightseal

FOLLOW UP ARTHROSCOPIC

Arthroscopic appearance of thesame area 12 months afterCarticeltrade implantation Thedefect is no longer visible andthere is now hyaline cartilage(biopsy proven) filling theoriginal defect site

REHABILITATION GUIDELINES

Immobilization first 12-24 hours

(CPM) after 12-24 hours for about 4 weeks

Complete joint loading from about 5th week trochleapatellafrom about 8th week condyle Back to sports Low impact rarr within 6 monthsRepeated impact rarr from 8th monthHigh impact rarr from 10-12th month

ACI REHABILITATION

Weight bearingIt is recommended to keep you in non-weight bearing until the second week after surgery (ACI) You can increase the weight bearing gradually and you may be able to sustain your full weight bearing after 6 to 12 weeks from surgery

Range of motionRecovery on your ROM (Range of Motion) is gradually increased with a continuous passive motion (CPM) machine and may be completed to 140 degrees of ROM at 6 weeks to 12 weeks after surgery

ACI REHABILITATIONIndoor exerciseYou can strenghthen your muscles surrounding the knee joint with a four point exercise as well as isometric hamstring and squatting exercises from 4 weeks to 6 weeks after surgeryYou may start performing stationary bike activity without resistance and increase the resistance gradually

Outdoor exerciseAt 13 weeks after surgery you can start walking lightly and at 10 months after surgery you can perform jogging and then you may enjoy intensity exercise like playing tennis or volleyball from 18 months after surgery

Rehabilitation Goals at 12 weeks after ACIFull ROM (Range of Motion) Minimal edema level Minimal occasional pain Pain free tolerance to transitional phase exercise with adequate stability and motor control

COMPARISON WITH OTHER METHODS OF TREATMENTS

Autologous Chondrocyte Implantation Aims to increase the best condition for cartilage defectAdvantagesbullHyaline cartilage is formed bullPermanent reconstructed cartilage tissue bullMost valuable treatment

bullWith Fourth Generation ACI Use of cell ndash gel mixture (collagen hyaluronic acid and fibrin) has fast gelling properties (1 ndash 5 min) upon transplantation bullNo membrane or periosteal patch bullMinimal surgical exposure and reduced surgery time bullCorrects evenly irregular defect shapes bullApplicable to larger defects

COMPARISON WITH OTHER METHODS OF TREATMENTShelliphelliphellip

Abrasion arthroplastyAims to decrease the inflammation of the jointDisadvantagesbullRemoves many cartilage fragments from the jointbullSymptoms reoccur within one year

Drilling and MicrofractureAims to generate a healing responseDisadvantagesbullThe healing response in inadequate bullNo hyaline cartilage is formed but rather fibrocartilage bullHas a limited lifespan of approximately one year bullRapid deterioration after such procedures can be expected

COMPARISON WITH OTHER METHODS OF TREATMENTShelliphelliphellip

Perichondral ResurfacingDisadvantagesbullIsolated cartilage defects are often too large to be covered byh perichondrum bullLong term follow-up of such procedures indicate that the implants undergo endochondral ossification

Synthetic Materials (ie Carbon Fiber Mesh)Disadvantagesbull It often results in fibrous tissue formation bullNot adequate biomechanically bullOften the cause for synovitis in the joints

Osteocartiloginous GraftsAims to reconstruct jointsDisadvantagesbullUnless fresh cartilage is transplanted the cartilage is dead bullFresh grafts are not commonly used as they inevitably carry a risk of disease transmission bullCyropreserved grafts can survive for many years but ultimately deteriorate

Results of the Carticeltrade procedure have been encouraging although it is not always successful An analysis was done of the US and Swedish registry of 153 consecutive patients undergoing this procedure with follow-up from 1 week to 94 months The following results were obtainedbull Patients with clinical improvement 85bull Good or Excellent results 42 bull Good or Excellent results at 2 yearspersisting at 5 years post-op 97

Thus a total of 85 of patients showed some or complete improvement with theimplantation technique The Carticel procedure demonstrated good durability at 5-10 years out

CONCLUSIONS

CONCLUSIONS ACI Vs MACI No current evidence to justify aggressive treatment of

asymptomatic lesions with ACIMACI

Patients with full thickness symptomatic defects do poorly if left untreated

ACI and MACI lead to significant improvement in objective and patient reported clinical outcome scores for up to ten years(even among those with previous failed marrow stimulation techniques)

MACI has a superior rate of clinical improvement in comparison to ACI

Repair tissue may remodel and improve in quality with time

ACI and MACI comparable at 6 years

RECENT ADVANCESHYAFF 3D MATRIX

HYAFF biomaterialscontain high quantities ofderivatized HA

HA-richchondrocyte compatibleembryonic-like mileuconductive to regenerativehealing patterns

bull Non woven felt 2 mm thick fiber diameter 10 micronsbull Chondrocytes are isolated and passaged in culture on plasticdishes up to 3 weeksbull Cells are seeded for 2 weeks on HYAFF scaffold at a density of1 x 106 cm2 resulting in a total of 4 x 106 cm2 seeded cells pergraft

HYAFF-BASED SCAFFOLD

CHONDRONtrade

Uses a cell ndash gel mixture (includes collagen hyaluronic acid and fibrin) that has fast gelling properties (1 ndash 5 min) upon transplantation

This cell and gel mixture enable even cell distribution three-dimensionally moldable to fit irregular defect shape and applicable to a larger defectThus there is minimal surgical exposure and reduced surgery time

(three-dimensional reconstruction of a chondron from the growth plate of the murine long bone the model was generated from multiple sections imaged in an electron microscope plasma membranes are coloured green and internal organelles are visible within the top cell)

RECOVERY TO

HEALTHY ACTIVE LIFE

THANK YOU

• journal club (22-10-09)
• topic autologus chondrocyte implantation
• THE ROLE OF AUTOLOGOUS CHONDROCYTE IMPLANTATION (ACI) IN THE TR
• Slide 4
• AUTOLOGOUS CHONDROCYTE GRAFTS MULTICENTRIC TRIAL WITH 28 KNEE
• Slide 6
• Slide 7
• Articular Cartilage
• Hyaline Cartilage Structure 1048715The ldquostuffrdquo of cartilage
• Slide 11
• Cartilage Injury Occurs in Many Forms
• Articular Cartilage Defects a treatment challenge
• AND WHAT IS IN OUR BASKET
• SO IT LED US TO SEARCH OF MORE PROMISING OPTION
• Autologous Chondrocyte Implantation (ACI) BACKGROUND
• Identifying a Carticelreg Patient
• Identifying a Carticelreg Patienthelliphellip
• Pre-requisite for surgery
• Autologous Chondrocyte Implantation (ACI)
• Techniques
• ACIMACI Generic Method
• Slide 23
• Treatment with CARTICEL
• CARTICEL Manufacturing and Delivery
• Step 2 Implantation
• CARTICEL Implantation
• Periosteal Patch
• Slide 29
• Slide 30
• Aci steps summarised
• Slide 32
• Complications
• Slide 34
• Slide 35
• FOLLOW UP Biopsy
• FOLLOW UP MRI
• FOLLOW UP ARTHROSCOPIC
• Rehabilitation guidelines
• ACI Rehabilitation
• ACI Rehabilitation (2)
• COMPARISON WITH OTHER METHODS OF TREATMENTS
• COMPARISON WITH OTHER METHODS OF TREATMENTShelliphelliphellip
• COMPARISON WITH OTHER METHODS OF TREATMENTShelliphelliphellip (2)
• CONCLUSIONS
• Slide 46
• Recent advancesHYAFF 3D matrix
• HYAFF-based Scaffold
• CHONDRONtrade
• RECOVERY TO
• Slide 51

PREVALENCE AND INCIDENCE

993 consecutive arthroscopies ndash 66 articular cartilage pathology 11 full thickness localised lesions suitable for repair procedures

Aroen A Loken S Heir S et al Am J Sports Med 2004 32 211-15

31000 arthroscopic procedures ndash 63 articular cartilage lesions

Curl WW Krome J Gordon ES et al Arthroscopy 1997 13 456-60

1000 consecutive arthroscopies ndash 19 localised chondralosteochondral lesionsHjelle K et al Arthroscopy 2002 18 730-4

CARTILAGE INJURY OCCURS IN MANY FORMS

Trauma sports or work related

Chronic instability long term effects ACL and othermeniscal deficiency

Mal-aligned joint - deformityvarus Valgus

Osteochondritis Dissecans [OCD]

Genetic pre-disposition earlyarthritis

bull Most full-thickness defects are symptomaticndash Pain swelling locking catching grinding

bull Left untreatedmay progress to significant articular defects

ARTICULAR CARTILAGE DEFECTS A TREATMENT CHALLENGE

bullMay lead to debilitatingosteoarthritis

Arthroscopic Debridement

Arthroscopic lavage

Subchondral drilling

Microfracture MARROW STIMULATION TECHNIQUES Abrasion arthroplasty -to induce the growth of fibrocartilage into the chondral defect (This fibrocartilage does not withstand shock or shearing force as well as the original hyaline cartilage and may deteriorate over time)

AND WHAT IS IN OUR BASKET

AUTOLOGUS CHONDROCYTE IMPLANTATION

SO IT LED US TO SEARCH OF MORE PROMISING OPTION

JBJS [Am] 1987 Peterson et al Gothenburgndash first application of cell engineering in orthopaedics

NEJM 1994 Brittberg et al Swedenndash successfuly regenerated hyaline-like cartilage in isolated chondral defects

AUTOLOGOUS CHONDROCYTE IMPLANTATION (ACI) BACKGROUND

IDENTIFYING A CARTICELreg PATIENT

Patient FactorsYounger patients ndash lt age 45 - 50 (avg ~ 35 yo)

Significant impairment-Compromised daily livingactivities -Refractory to treatment

Obesity

Demanding Physical activities

Willing amp capable of rehabilitation program

IDENTIFYING A CARTICELreg PATIENThelliphellip

Joint FactorsSymptomatic cartilage defects -Moderate to large (gt 2cm2 d= 16) -On the distal femur (mfc lfc trochlea) -Average defect size gt 4 cm2

-Either chondral or osteochondral

Relatively healthy joint ndash -No arthritis

Co-morbidities(meniscal tear

instability or malalignment) must be corrected prior or concurrent to implantation

Pre-requisite for surgery

Not recommended for patients who have

Appropriate biomachenical alignment

Ligamentous stabilty

Range of motion

an unstable knee

patients sensitive to materials of bovine origins

allergic to the antibiotic gentamicin

in children

yet in any joint other than the knee

AUTOLOGOUS CHONDROCYTEIMPLANTATION (ACI)

StrengthsCan produce hyaline-like cartilageCan fill defects regardless of size with functional repair tissueModerate to large defects that have failed previous interventionRepair tissue which matures rather than deteriorates over timeExpected outcomeReturn to previous level of functioning

ldquoBiological Joint replacementrdquo

LimitationsMore invasiveExpenseLonger recovery

A ACI ndash Periosteum (cells under periosteum)

B ACI ndash Chondrogide (cells under membrane)

C MACI ndash Matrix Induced ACI (cells on membrane)

Chondrogide Membrane Porcine type IIII Inert Seal Resorbs in 3-4 months

ACI MACI

TECHNIQUES

Under inert collagen membrane (ACI)

On inert collagen membrane (MACI)

Harvest 200-300mg full thickness cartilage from trochlea (non load bearing)

Cells grown on monolayer with patients serum

No cells x 20-30

ACIMACI GENERIC METHOD

ACI METHOD

TREATMENT WITH CARTICEL

Uses your own cartilage cells (chondrocytes) to repair the articular cartilage damage in your knee When implanted into a cartilage injury your own cells can form new cartilage this new cartilage is very similar to your original cartilage The CARTICEL implantation procedure is called Autologous Chondrocyte Implantation or ACI It is a two-step process

Knee Cartilage Arthroscopy and BiopsyDuring an arthroscopic procedure surgeon assesses the extent of cartilage damage amp pt as a candidate for CARTICEL implantation

ldquoBiopsyrdquo of healthy tissue about the size of a pencil eraser ie about 200 -300 mg

From outer edge of sup Med or lat Femoral condyle or inner edge of lat Femoral condyle at the intercondylar notch

This sample is sent to product labs

Step 1 Biopsy

Biopsy can be stored for up to two years so you can schedule your surgery at your convenience

When you are ready your cells are cultured over three to five weeks they increase to approx 12 million cells in a vial containing 03 ndash 04 cc of medium Every step of the manufacturing process is monitored to ensure high quality and safety

CARTICEL MANUFACTURING AND DELIVERY

STEP 2 IMPLANTATION

Cartilage Injury CleanedDuring this second stage arthrotomy done to expose knee and any dead or damaged tissue from the injury removed with curette leaving only healthy tissue

Biomachenical allignment procedures if required should be done in conjunction with implantation

CARTICEL IMPLANTATION

PERIOSTEAL PATCH

surgeon takes a small piece of tissue from your shin bone and sews it securely over the injury

CARTICEL Implantation surgeon injects CARTICEL under the patch

When CARTICEL is surgically implanted into a cartilage injury it can grow and form new hyaline-like cartilage with properties similar to those of the original cartilage

Repairing the injury helps to reduce pain and improve movement and function

ACI STEPS summarised

MACI METHOD

Cultured chondrocytes seeded in bilayered typeIIII collagen membrane

Implanted using fibrin glue

Matrix remodelled in months replaced by extracellular matrix regenerate

The overall failure rate is at present quoted as being 10 The two most common complications include bullloosening of the transplant tissue bullformation of fibrous tissue at the repair site and adhesions with return of pain and locking Neither of these complications usually leaves the patient in a worse condition than hisher pre-transplantation state

Other adverse events include bullpost-op haematoma (big blood clot)bullhypertrophic synovitis (angry knee) and superficial wound infection

COMPLICATIONS

IMPROVEMENTS IN CLINICAL OUTCOME

ASSESMENT OF TECHNIQUE

FOLLOW UP RESULTS

ONE YEAR ASSESSMENT

Radiographs Alignment Bone quality

MRI Healing

cartilage Graft failure

Arthroscopy + probe Graft integrity Pressure biopsy

FOLLOW UP BIOPSY

FOLLOW UP MRI

Final appearance of theperiosteum sutured overfemoral condyle defect Thecartilage cells have beeninjected under the flap and thefinal suture placed to close thecover and provide a watertightseal

FOLLOW UP ARTHROSCOPIC

Arthroscopic appearance of thesame area 12 months afterCarticeltrade implantation Thedefect is no longer visible andthere is now hyaline cartilage(biopsy proven) filling theoriginal defect site

REHABILITATION GUIDELINES

Immobilization first 12-24 hours

(CPM) after 12-24 hours for about 4 weeks

Complete joint loading from about 5th week trochleapatellafrom about 8th week condyle Back to sports Low impact rarr within 6 monthsRepeated impact rarr from 8th monthHigh impact rarr from 10-12th month

ACI REHABILITATION

Weight bearingIt is recommended to keep you in non-weight bearing until the second week after surgery (ACI) You can increase the weight bearing gradually and you may be able to sustain your full weight bearing after 6 to 12 weeks from surgery

Range of motionRecovery on your ROM (Range of Motion) is gradually increased with a continuous passive motion (CPM) machine and may be completed to 140 degrees of ROM at 6 weeks to 12 weeks after surgery

ACI REHABILITATIONIndoor exerciseYou can strenghthen your muscles surrounding the knee joint with a four point exercise as well as isometric hamstring and squatting exercises from 4 weeks to 6 weeks after surgeryYou may start performing stationary bike activity without resistance and increase the resistance gradually

Outdoor exerciseAt 13 weeks after surgery you can start walking lightly and at 10 months after surgery you can perform jogging and then you may enjoy intensity exercise like playing tennis or volleyball from 18 months after surgery

Rehabilitation Goals at 12 weeks after ACIFull ROM (Range of Motion) Minimal edema level Minimal occasional pain Pain free tolerance to transitional phase exercise with adequate stability and motor control

COMPARISON WITH OTHER METHODS OF TREATMENTS

Autologous Chondrocyte Implantation Aims to increase the best condition for cartilage defectAdvantagesbullHyaline cartilage is formed bullPermanent reconstructed cartilage tissue bullMost valuable treatment

bullWith Fourth Generation ACI Use of cell ndash gel mixture (collagen hyaluronic acid and fibrin) has fast gelling properties (1 ndash 5 min) upon transplantation bullNo membrane or periosteal patch bullMinimal surgical exposure and reduced surgery time bullCorrects evenly irregular defect shapes bullApplicable to larger defects

COMPARISON WITH OTHER METHODS OF TREATMENTShelliphelliphellip

Abrasion arthroplastyAims to decrease the inflammation of the jointDisadvantagesbullRemoves many cartilage fragments from the jointbullSymptoms reoccur within one year

Drilling and MicrofractureAims to generate a healing responseDisadvantagesbullThe healing response in inadequate bullNo hyaline cartilage is formed but rather fibrocartilage bullHas a limited lifespan of approximately one year bullRapid deterioration after such procedures can be expected

COMPARISON WITH OTHER METHODS OF TREATMENTShelliphelliphellip

Perichondral ResurfacingDisadvantagesbullIsolated cartilage defects are often too large to be covered byh perichondrum bullLong term follow-up of such procedures indicate that the implants undergo endochondral ossification

Synthetic Materials (ie Carbon Fiber Mesh)Disadvantagesbull It often results in fibrous tissue formation bullNot adequate biomechanically bullOften the cause for synovitis in the joints

Osteocartiloginous GraftsAims to reconstruct jointsDisadvantagesbullUnless fresh cartilage is transplanted the cartilage is dead bullFresh grafts are not commonly used as they inevitably carry a risk of disease transmission bullCyropreserved grafts can survive for many years but ultimately deteriorate

Results of the Carticeltrade procedure have been encouraging although it is not always successful An analysis was done of the US and Swedish registry of 153 consecutive patients undergoing this procedure with follow-up from 1 week to 94 months The following results were obtainedbull Patients with clinical improvement 85bull Good or Excellent results 42 bull Good or Excellent results at 2 yearspersisting at 5 years post-op 97

Thus a total of 85 of patients showed some or complete improvement with theimplantation technique The Carticel procedure demonstrated good durability at 5-10 years out

CONCLUSIONS

CONCLUSIONS ACI Vs MACI No current evidence to justify aggressive treatment of

asymptomatic lesions with ACIMACI

Patients with full thickness symptomatic defects do poorly if left untreated

ACI and MACI lead to significant improvement in objective and patient reported clinical outcome scores for up to ten years(even among those with previous failed marrow stimulation techniques)

MACI has a superior rate of clinical improvement in comparison to ACI

Repair tissue may remodel and improve in quality with time

ACI and MACI comparable at 6 years

RECENT ADVANCESHYAFF 3D MATRIX

HYAFF biomaterialscontain high quantities ofderivatized HA

HA-richchondrocyte compatibleembryonic-like mileuconductive to regenerativehealing patterns

bull Non woven felt 2 mm thick fiber diameter 10 micronsbull Chondrocytes are isolated and passaged in culture on plasticdishes up to 3 weeksbull Cells are seeded for 2 weeks on HYAFF scaffold at a density of1 x 106 cm2 resulting in a total of 4 x 106 cm2 seeded cells pergraft

HYAFF-BASED SCAFFOLD

CHONDRONtrade

Uses a cell ndash gel mixture (includes collagen hyaluronic acid and fibrin) that has fast gelling properties (1 ndash 5 min) upon transplantation

This cell and gel mixture enable even cell distribution three-dimensionally moldable to fit irregular defect shape and applicable to a larger defectThus there is minimal surgical exposure and reduced surgery time

(three-dimensional reconstruction of a chondron from the growth plate of the murine long bone the model was generated from multiple sections imaged in an electron microscope plasma membranes are coloured green and internal organelles are visible within the top cell)

RECOVERY TO

HEALTHY ACTIVE LIFE

THANK YOU

• journal club (22-10-09)
• topic autologus chondrocyte implantation
• THE ROLE OF AUTOLOGOUS CHONDROCYTE IMPLANTATION (ACI) IN THE TR
• Slide 4
• AUTOLOGOUS CHONDROCYTE GRAFTS MULTICENTRIC TRIAL WITH 28 KNEE
• Slide 6
• Slide 7
• Articular Cartilage
• Hyaline Cartilage Structure 1048715The ldquostuffrdquo of cartilage
• Slide 11
• Cartilage Injury Occurs in Many Forms
• Articular Cartilage Defects a treatment challenge
• AND WHAT IS IN OUR BASKET
• SO IT LED US TO SEARCH OF MORE PROMISING OPTION
• Autologous Chondrocyte Implantation (ACI) BACKGROUND
• Identifying a Carticelreg Patient
• Identifying a Carticelreg Patienthelliphellip
• Pre-requisite for surgery
• Autologous Chondrocyte Implantation (ACI)
• Techniques
• ACIMACI Generic Method
• Slide 23
• Treatment with CARTICEL
• CARTICEL Manufacturing and Delivery
• Step 2 Implantation
• CARTICEL Implantation
• Periosteal Patch
• Slide 29
• Slide 30
• Aci steps summarised
• Slide 32
• Complications
• Slide 34
• Slide 35
• FOLLOW UP Biopsy
• FOLLOW UP MRI
• FOLLOW UP ARTHROSCOPIC
• Rehabilitation guidelines
• ACI Rehabilitation
• ACI Rehabilitation (2)
• COMPARISON WITH OTHER METHODS OF TREATMENTS
• COMPARISON WITH OTHER METHODS OF TREATMENTShelliphelliphellip
• COMPARISON WITH OTHER METHODS OF TREATMENTShelliphelliphellip (2)
• CONCLUSIONS
• Slide 46
• Recent advancesHYAFF 3D matrix
• HYAFF-based Scaffold
• CHONDRONtrade
• RECOVERY TO
• Slide 51

CARTILAGE INJURY OCCURS IN MANY FORMS

Trauma sports or work related

Chronic instability long term effects ACL and othermeniscal deficiency

Mal-aligned joint - deformityvarus Valgus

Osteochondritis Dissecans [OCD]

Genetic pre-disposition earlyarthritis

bull Most full-thickness defects are symptomaticndash Pain swelling locking catching grinding

bull Left untreatedmay progress to significant articular defects

ARTICULAR CARTILAGE DEFECTS A TREATMENT CHALLENGE

bullMay lead to debilitatingosteoarthritis

Arthroscopic Debridement

Arthroscopic lavage

Subchondral drilling

Microfracture MARROW STIMULATION TECHNIQUES Abrasion arthroplasty -to induce the growth of fibrocartilage into the chondral defect (This fibrocartilage does not withstand shock or shearing force as well as the original hyaline cartilage and may deteriorate over time)

AND WHAT IS IN OUR BASKET

AUTOLOGUS CHONDROCYTE IMPLANTATION

SO IT LED US TO SEARCH OF MORE PROMISING OPTION

JBJS [Am] 1987 Peterson et al Gothenburgndash first application of cell engineering in orthopaedics

NEJM 1994 Brittberg et al Swedenndash successfuly regenerated hyaline-like cartilage in isolated chondral defects

AUTOLOGOUS CHONDROCYTE IMPLANTATION (ACI) BACKGROUND

IDENTIFYING A CARTICELreg PATIENT

Patient FactorsYounger patients ndash lt age 45 - 50 (avg ~ 35 yo)

Significant impairment-Compromised daily livingactivities -Refractory to treatment

Obesity

Demanding Physical activities

Willing amp capable of rehabilitation program

IDENTIFYING A CARTICELreg PATIENThelliphellip

Joint FactorsSymptomatic cartilage defects -Moderate to large (gt 2cm2 d= 16) -On the distal femur (mfc lfc trochlea) -Average defect size gt 4 cm2

-Either chondral or osteochondral

Relatively healthy joint ndash -No arthritis

Co-morbidities(meniscal tear

instability or malalignment) must be corrected prior or concurrent to implantation

Pre-requisite for surgery

Not recommended for patients who have

Appropriate biomachenical alignment

Ligamentous stabilty

Range of motion

an unstable knee

patients sensitive to materials of bovine origins

allergic to the antibiotic gentamicin

in children

yet in any joint other than the knee

AUTOLOGOUS CHONDROCYTEIMPLANTATION (ACI)

StrengthsCan produce hyaline-like cartilageCan fill defects regardless of size with functional repair tissueModerate to large defects that have failed previous interventionRepair tissue which matures rather than deteriorates over timeExpected outcomeReturn to previous level of functioning

ldquoBiological Joint replacementrdquo

LimitationsMore invasiveExpenseLonger recovery

A ACI ndash Periosteum (cells under periosteum)

B ACI ndash Chondrogide (cells under membrane)

C MACI ndash Matrix Induced ACI (cells on membrane)

Chondrogide Membrane Porcine type IIII Inert Seal Resorbs in 3-4 months

ACI MACI

TECHNIQUES

Under inert collagen membrane (ACI)

On inert collagen membrane (MACI)

Harvest 200-300mg full thickness cartilage from trochlea (non load bearing)

Cells grown on monolayer with patients serum

No cells x 20-30

ACIMACI GENERIC METHOD

ACI METHOD

TREATMENT WITH CARTICEL

Uses your own cartilage cells (chondrocytes) to repair the articular cartilage damage in your knee When implanted into a cartilage injury your own cells can form new cartilage this new cartilage is very similar to your original cartilage The CARTICEL implantation procedure is called Autologous Chondrocyte Implantation or ACI It is a two-step process

Knee Cartilage Arthroscopy and BiopsyDuring an arthroscopic procedure surgeon assesses the extent of cartilage damage amp pt as a candidate for CARTICEL implantation

ldquoBiopsyrdquo of healthy tissue about the size of a pencil eraser ie about 200 -300 mg

From outer edge of sup Med or lat Femoral condyle or inner edge of lat Femoral condyle at the intercondylar notch

This sample is sent to product labs

Step 1 Biopsy

Biopsy can be stored for up to two years so you can schedule your surgery at your convenience

When you are ready your cells are cultured over three to five weeks they increase to approx 12 million cells in a vial containing 03 ndash 04 cc of medium Every step of the manufacturing process is monitored to ensure high quality and safety

CARTICEL MANUFACTURING AND DELIVERY

STEP 2 IMPLANTATION

Cartilage Injury CleanedDuring this second stage arthrotomy done to expose knee and any dead or damaged tissue from the injury removed with curette leaving only healthy tissue

Biomachenical allignment procedures if required should be done in conjunction with implantation

CARTICEL IMPLANTATION

PERIOSTEAL PATCH

surgeon takes a small piece of tissue from your shin bone and sews it securely over the injury

CARTICEL Implantation surgeon injects CARTICEL under the patch

When CARTICEL is surgically implanted into a cartilage injury it can grow and form new hyaline-like cartilage with properties similar to those of the original cartilage

Repairing the injury helps to reduce pain and improve movement and function

ACI STEPS summarised

MACI METHOD

Cultured chondrocytes seeded in bilayered typeIIII collagen membrane

Implanted using fibrin glue

Matrix remodelled in months replaced by extracellular matrix regenerate

The overall failure rate is at present quoted as being 10 The two most common complications include bullloosening of the transplant tissue bullformation of fibrous tissue at the repair site and adhesions with return of pain and locking Neither of these complications usually leaves the patient in a worse condition than hisher pre-transplantation state

Other adverse events include bullpost-op haematoma (big blood clot)bullhypertrophic synovitis (angry knee) and superficial wound infection

COMPLICATIONS

IMPROVEMENTS IN CLINICAL OUTCOME

ASSESMENT OF TECHNIQUE

FOLLOW UP RESULTS

ONE YEAR ASSESSMENT

Radiographs Alignment Bone quality

MRI Healing

cartilage Graft failure

Arthroscopy + probe Graft integrity Pressure biopsy

FOLLOW UP BIOPSY

FOLLOW UP MRI

Final appearance of theperiosteum sutured overfemoral condyle defect Thecartilage cells have beeninjected under the flap and thefinal suture placed to close thecover and provide a watertightseal

FOLLOW UP ARTHROSCOPIC

Arthroscopic appearance of thesame area 12 months afterCarticeltrade implantation Thedefect is no longer visible andthere is now hyaline cartilage(biopsy proven) filling theoriginal defect site

REHABILITATION GUIDELINES

Immobilization first 12-24 hours

(CPM) after 12-24 hours for about 4 weeks

Complete joint loading from about 5th week trochleapatellafrom about 8th week condyle Back to sports Low impact rarr within 6 monthsRepeated impact rarr from 8th monthHigh impact rarr from 10-12th month

ACI REHABILITATION

Weight bearingIt is recommended to keep you in non-weight bearing until the second week after surgery (ACI) You can increase the weight bearing gradually and you may be able to sustain your full weight bearing after 6 to 12 weeks from surgery

Range of motionRecovery on your ROM (Range of Motion) is gradually increased with a continuous passive motion (CPM) machine and may be completed to 140 degrees of ROM at 6 weeks to 12 weeks after surgery

ACI REHABILITATIONIndoor exerciseYou can strenghthen your muscles surrounding the knee joint with a four point exercise as well as isometric hamstring and squatting exercises from 4 weeks to 6 weeks after surgeryYou may start performing stationary bike activity without resistance and increase the resistance gradually

Outdoor exerciseAt 13 weeks after surgery you can start walking lightly and at 10 months after surgery you can perform jogging and then you may enjoy intensity exercise like playing tennis or volleyball from 18 months after surgery

Rehabilitation Goals at 12 weeks after ACIFull ROM (Range of Motion) Minimal edema level Minimal occasional pain Pain free tolerance to transitional phase exercise with adequate stability and motor control

COMPARISON WITH OTHER METHODS OF TREATMENTS

Autologous Chondrocyte Implantation Aims to increase the best condition for cartilage defectAdvantagesbullHyaline cartilage is formed bullPermanent reconstructed cartilage tissue bullMost valuable treatment

bullWith Fourth Generation ACI Use of cell ndash gel mixture (collagen hyaluronic acid and fibrin) has fast gelling properties (1 ndash 5 min) upon transplantation bullNo membrane or periosteal patch bullMinimal surgical exposure and reduced surgery time bullCorrects evenly irregular defect shapes bullApplicable to larger defects

COMPARISON WITH OTHER METHODS OF TREATMENTShelliphelliphellip

Abrasion arthroplastyAims to decrease the inflammation of the jointDisadvantagesbullRemoves many cartilage fragments from the jointbullSymptoms reoccur within one year

Drilling and MicrofractureAims to generate a healing responseDisadvantagesbullThe healing response in inadequate bullNo hyaline cartilage is formed but rather fibrocartilage bullHas a limited lifespan of approximately one year bullRapid deterioration after such procedures can be expected

COMPARISON WITH OTHER METHODS OF TREATMENTShelliphelliphellip

Perichondral ResurfacingDisadvantagesbullIsolated cartilage defects are often too large to be covered byh perichondrum bullLong term follow-up of such procedures indicate that the implants undergo endochondral ossification

Synthetic Materials (ie Carbon Fiber Mesh)Disadvantagesbull It often results in fibrous tissue formation bullNot adequate biomechanically bullOften the cause for synovitis in the joints

Osteocartiloginous GraftsAims to reconstruct jointsDisadvantagesbullUnless fresh cartilage is transplanted the cartilage is dead bullFresh grafts are not commonly used as they inevitably carry a risk of disease transmission bullCyropreserved grafts can survive for many years but ultimately deteriorate

Results of the Carticeltrade procedure have been encouraging although it is not always successful An analysis was done of the US and Swedish registry of 153 consecutive patients undergoing this procedure with follow-up from 1 week to 94 months The following results were obtainedbull Patients with clinical improvement 85bull Good or Excellent results 42 bull Good or Excellent results at 2 yearspersisting at 5 years post-op 97

Thus a total of 85 of patients showed some or complete improvement with theimplantation technique The Carticel procedure demonstrated good durability at 5-10 years out

CONCLUSIONS

CONCLUSIONS ACI Vs MACI No current evidence to justify aggressive treatment of

asymptomatic lesions with ACIMACI

Patients with full thickness symptomatic defects do poorly if left untreated

ACI and MACI lead to significant improvement in objective and patient reported clinical outcome scores for up to ten years(even among those with previous failed marrow stimulation techniques)

MACI has a superior rate of clinical improvement in comparison to ACI

Repair tissue may remodel and improve in quality with time

ACI and MACI comparable at 6 years

RECENT ADVANCESHYAFF 3D MATRIX

HYAFF biomaterialscontain high quantities ofderivatized HA

HA-richchondrocyte compatibleembryonic-like mileuconductive to regenerativehealing patterns

bull Non woven felt 2 mm thick fiber diameter 10 micronsbull Chondrocytes are isolated and passaged in culture on plasticdishes up to 3 weeksbull Cells are seeded for 2 weeks on HYAFF scaffold at a density of1 x 106 cm2 resulting in a total of 4 x 106 cm2 seeded cells pergraft

HYAFF-BASED SCAFFOLD

CHONDRONtrade

Uses a cell ndash gel mixture (includes collagen hyaluronic acid and fibrin) that has fast gelling properties (1 ndash 5 min) upon transplantation

This cell and gel mixture enable even cell distribution three-dimensionally moldable to fit irregular defect shape and applicable to a larger defectThus there is minimal surgical exposure and reduced surgery time

(three-dimensional reconstruction of a chondron from the growth plate of the murine long bone the model was generated from multiple sections imaged in an electron microscope plasma membranes are coloured green and internal organelles are visible within the top cell)

RECOVERY TO

HEALTHY ACTIVE LIFE

THANK YOU

• journal club (22-10-09)
• topic autologus chondrocyte implantation
• THE ROLE OF AUTOLOGOUS CHONDROCYTE IMPLANTATION (ACI) IN THE TR
• Slide 4
• AUTOLOGOUS CHONDROCYTE GRAFTS MULTICENTRIC TRIAL WITH 28 KNEE
• Slide 6
• Slide 7
• Articular Cartilage
• Hyaline Cartilage Structure 1048715The ldquostuffrdquo of cartilage
• Slide 11
• Cartilage Injury Occurs in Many Forms
• Articular Cartilage Defects a treatment challenge
• AND WHAT IS IN OUR BASKET
• SO IT LED US TO SEARCH OF MORE PROMISING OPTION
• Autologous Chondrocyte Implantation (ACI) BACKGROUND
• Identifying a Carticelreg Patient
• Identifying a Carticelreg Patienthelliphellip
• Pre-requisite for surgery
• Autologous Chondrocyte Implantation (ACI)
• Techniques
• ACIMACI Generic Method
• Slide 23
• Treatment with CARTICEL
• CARTICEL Manufacturing and Delivery
• Step 2 Implantation
• CARTICEL Implantation
• Periosteal Patch
• Slide 29
• Slide 30
• Aci steps summarised
• Slide 32
• Complications
• Slide 34
• Slide 35
• FOLLOW UP Biopsy
• FOLLOW UP MRI
• FOLLOW UP ARTHROSCOPIC
• Rehabilitation guidelines
• ACI Rehabilitation
• ACI Rehabilitation (2)
• COMPARISON WITH OTHER METHODS OF TREATMENTS
• COMPARISON WITH OTHER METHODS OF TREATMENTShelliphelliphellip
• COMPARISON WITH OTHER METHODS OF TREATMENTShelliphelliphellip (2)
• CONCLUSIONS
• Slide 46
• Recent advancesHYAFF 3D matrix
• HYAFF-based Scaffold
• CHONDRONtrade
• RECOVERY TO
• Slide 51

bull Most full-thickness defects are symptomaticndash Pain swelling locking catching grinding

bull Left untreatedmay progress to significant articular defects

ARTICULAR CARTILAGE DEFECTS A TREATMENT CHALLENGE

bullMay lead to debilitatingosteoarthritis

Arthroscopic Debridement

Arthroscopic lavage

Subchondral drilling

Microfracture MARROW STIMULATION TECHNIQUES Abrasion arthroplasty -to induce the growth of fibrocartilage into the chondral defect (This fibrocartilage does not withstand shock or shearing force as well as the original hyaline cartilage and may deteriorate over time)

AND WHAT IS IN OUR BASKET

AUTOLOGUS CHONDROCYTE IMPLANTATION

SO IT LED US TO SEARCH OF MORE PROMISING OPTION

JBJS [Am] 1987 Peterson et al Gothenburgndash first application of cell engineering in orthopaedics

NEJM 1994 Brittberg et al Swedenndash successfuly regenerated hyaline-like cartilage in isolated chondral defects

AUTOLOGOUS CHONDROCYTE IMPLANTATION (ACI) BACKGROUND

IDENTIFYING A CARTICELreg PATIENT

Patient FactorsYounger patients ndash lt age 45 - 50 (avg ~ 35 yo)

Significant impairment-Compromised daily livingactivities -Refractory to treatment

Obesity

Demanding Physical activities

Willing amp capable of rehabilitation program

IDENTIFYING A CARTICELreg PATIENThelliphellip

Joint FactorsSymptomatic cartilage defects -Moderate to large (gt 2cm2 d= 16) -On the distal femur (mfc lfc trochlea) -Average defect size gt 4 cm2

-Either chondral or osteochondral

Relatively healthy joint ndash -No arthritis

Co-morbidities(meniscal tear

instability or malalignment) must be corrected prior or concurrent to implantation

Pre-requisite for surgery

Not recommended for patients who have

Appropriate biomachenical alignment

Ligamentous stabilty

Range of motion

an unstable knee

patients sensitive to materials of bovine origins

allergic to the antibiotic gentamicin

in children

yet in any joint other than the knee

AUTOLOGOUS CHONDROCYTEIMPLANTATION (ACI)

StrengthsCan produce hyaline-like cartilageCan fill defects regardless of size with functional repair tissueModerate to large defects that have failed previous interventionRepair tissue which matures rather than deteriorates over timeExpected outcomeReturn to previous level of functioning

ldquoBiological Joint replacementrdquo

LimitationsMore invasiveExpenseLonger recovery

A ACI ndash Periosteum (cells under periosteum)

B ACI ndash Chondrogide (cells under membrane)

C MACI ndash Matrix Induced ACI (cells on membrane)

Chondrogide Membrane Porcine type IIII Inert Seal Resorbs in 3-4 months

ACI MACI

TECHNIQUES

Under inert collagen membrane (ACI)

On inert collagen membrane (MACI)

Harvest 200-300mg full thickness cartilage from trochlea (non load bearing)

Cells grown on monolayer with patients serum

No cells x 20-30

ACIMACI GENERIC METHOD

ACI METHOD

TREATMENT WITH CARTICEL

Uses your own cartilage cells (chondrocytes) to repair the articular cartilage damage in your knee When implanted into a cartilage injury your own cells can form new cartilage this new cartilage is very similar to your original cartilage The CARTICEL implantation procedure is called Autologous Chondrocyte Implantation or ACI It is a two-step process

Knee Cartilage Arthroscopy and BiopsyDuring an arthroscopic procedure surgeon assesses the extent of cartilage damage amp pt as a candidate for CARTICEL implantation

ldquoBiopsyrdquo of healthy tissue about the size of a pencil eraser ie about 200 -300 mg

From outer edge of sup Med or lat Femoral condyle or inner edge of lat Femoral condyle at the intercondylar notch

This sample is sent to product labs

Step 1 Biopsy

Biopsy can be stored for up to two years so you can schedule your surgery at your convenience

When you are ready your cells are cultured over three to five weeks they increase to approx 12 million cells in a vial containing 03 ndash 04 cc of medium Every step of the manufacturing process is monitored to ensure high quality and safety

CARTICEL MANUFACTURING AND DELIVERY

STEP 2 IMPLANTATION

Cartilage Injury CleanedDuring this second stage arthrotomy done to expose knee and any dead or damaged tissue from the injury removed with curette leaving only healthy tissue

Biomachenical allignment procedures if required should be done in conjunction with implantation

CARTICEL IMPLANTATION

PERIOSTEAL PATCH

surgeon takes a small piece of tissue from your shin bone and sews it securely over the injury

CARTICEL Implantation surgeon injects CARTICEL under the patch

When CARTICEL is surgically implanted into a cartilage injury it can grow and form new hyaline-like cartilage with properties similar to those of the original cartilage

Repairing the injury helps to reduce pain and improve movement and function

ACI STEPS summarised

MACI METHOD

Cultured chondrocytes seeded in bilayered typeIIII collagen membrane

Implanted using fibrin glue

Matrix remodelled in months replaced by extracellular matrix regenerate

The overall failure rate is at present quoted as being 10 The two most common complications include bullloosening of the transplant tissue bullformation of fibrous tissue at the repair site and adhesions with return of pain and locking Neither of these complications usually leaves the patient in a worse condition than hisher pre-transplantation state

Other adverse events include bullpost-op haematoma (big blood clot)bullhypertrophic synovitis (angry knee) and superficial wound infection

COMPLICATIONS

IMPROVEMENTS IN CLINICAL OUTCOME

ASSESMENT OF TECHNIQUE

FOLLOW UP RESULTS

ONE YEAR ASSESSMENT

Radiographs Alignment Bone quality

MRI Healing

cartilage Graft failure

Arthroscopy + probe Graft integrity Pressure biopsy

FOLLOW UP BIOPSY

FOLLOW UP MRI

Final appearance of theperiosteum sutured overfemoral condyle defect Thecartilage cells have beeninjected under the flap and thefinal suture placed to close thecover and provide a watertightseal

FOLLOW UP ARTHROSCOPIC

Arthroscopic appearance of thesame area 12 months afterCarticeltrade implantation Thedefect is no longer visible andthere is now hyaline cartilage(biopsy proven) filling theoriginal defect site

REHABILITATION GUIDELINES

Immobilization first 12-24 hours

(CPM) after 12-24 hours for about 4 weeks

Complete joint loading from about 5th week trochleapatellafrom about 8th week condyle Back to sports Low impact rarr within 6 monthsRepeated impact rarr from 8th monthHigh impact rarr from 10-12th month

ACI REHABILITATION

Weight bearingIt is recommended to keep you in non-weight bearing until the second week after surgery (ACI) You can increase the weight bearing gradually and you may be able to sustain your full weight bearing after 6 to 12 weeks from surgery

Range of motionRecovery on your ROM (Range of Motion) is gradually increased with a continuous passive motion (CPM) machine and may be completed to 140 degrees of ROM at 6 weeks to 12 weeks after surgery

ACI REHABILITATIONIndoor exerciseYou can strenghthen your muscles surrounding the knee joint with a four point exercise as well as isometric hamstring and squatting exercises from 4 weeks to 6 weeks after surgeryYou may start performing stationary bike activity without resistance and increase the resistance gradually

Outdoor exerciseAt 13 weeks after surgery you can start walking lightly and at 10 months after surgery you can perform jogging and then you may enjoy intensity exercise like playing tennis or volleyball from 18 months after surgery

Rehabilitation Goals at 12 weeks after ACIFull ROM (Range of Motion) Minimal edema level Minimal occasional pain Pain free tolerance to transitional phase exercise with adequate stability and motor control

COMPARISON WITH OTHER METHODS OF TREATMENTS

Autologous Chondrocyte Implantation Aims to increase the best condition for cartilage defectAdvantagesbullHyaline cartilage is formed bullPermanent reconstructed cartilage tissue bullMost valuable treatment

bullWith Fourth Generation ACI Use of cell ndash gel mixture (collagen hyaluronic acid and fibrin) has fast gelling properties (1 ndash 5 min) upon transplantation bullNo membrane or periosteal patch bullMinimal surgical exposure and reduced surgery time bullCorrects evenly irregular defect shapes bullApplicable to larger defects

COMPARISON WITH OTHER METHODS OF TREATMENTShelliphelliphellip

Abrasion arthroplastyAims to decrease the inflammation of the jointDisadvantagesbullRemoves many cartilage fragments from the jointbullSymptoms reoccur within one year

Drilling and MicrofractureAims to generate a healing responseDisadvantagesbullThe healing response in inadequate bullNo hyaline cartilage is formed but rather fibrocartilage bullHas a limited lifespan of approximately one year bullRapid deterioration after such procedures can be expected

COMPARISON WITH OTHER METHODS OF TREATMENTShelliphelliphellip

Perichondral ResurfacingDisadvantagesbullIsolated cartilage defects are often too large to be covered byh perichondrum bullLong term follow-up of such procedures indicate that the implants undergo endochondral ossification

Synthetic Materials (ie Carbon Fiber Mesh)Disadvantagesbull It often results in fibrous tissue formation bullNot adequate biomechanically bullOften the cause for synovitis in the joints

Osteocartiloginous GraftsAims to reconstruct jointsDisadvantagesbullUnless fresh cartilage is transplanted the cartilage is dead bullFresh grafts are not commonly used as they inevitably carry a risk of disease transmission bullCyropreserved grafts can survive for many years but ultimately deteriorate

Results of the Carticeltrade procedure have been encouraging although it is not always successful An analysis was done of the US and Swedish registry of 153 consecutive patients undergoing this procedure with follow-up from 1 week to 94 months The following results were obtainedbull Patients with clinical improvement 85bull Good or Excellent results 42 bull Good or Excellent results at 2 yearspersisting at 5 years post-op 97

Thus a total of 85 of patients showed some or complete improvement with theimplantation technique The Carticel procedure demonstrated good durability at 5-10 years out

CONCLUSIONS

CONCLUSIONS ACI Vs MACI No current evidence to justify aggressive treatment of

asymptomatic lesions with ACIMACI

Patients with full thickness symptomatic defects do poorly if left untreated

ACI and MACI lead to significant improvement in objective and patient reported clinical outcome scores for up to ten years(even among those with previous failed marrow stimulation techniques)

MACI has a superior rate of clinical improvement in comparison to ACI

Repair tissue may remodel and improve in quality with time

ACI and MACI comparable at 6 years

RECENT ADVANCESHYAFF 3D MATRIX

HYAFF biomaterialscontain high quantities ofderivatized HA

HA-richchondrocyte compatibleembryonic-like mileuconductive to regenerativehealing patterns

bull Non woven felt 2 mm thick fiber diameter 10 micronsbull Chondrocytes are isolated and passaged in culture on plasticdishes up to 3 weeksbull Cells are seeded for 2 weeks on HYAFF scaffold at a density of1 x 106 cm2 resulting in a total of 4 x 106 cm2 seeded cells pergraft

HYAFF-BASED SCAFFOLD

CHONDRONtrade

Uses a cell ndash gel mixture (includes collagen hyaluronic acid and fibrin) that has fast gelling properties (1 ndash 5 min) upon transplantation

This cell and gel mixture enable even cell distribution three-dimensionally moldable to fit irregular defect shape and applicable to a larger defectThus there is minimal surgical exposure and reduced surgery time

(three-dimensional reconstruction of a chondron from the growth plate of the murine long bone the model was generated from multiple sections imaged in an electron microscope plasma membranes are coloured green and internal organelles are visible within the top cell)

RECOVERY TO

HEALTHY ACTIVE LIFE

THANK YOU

• journal club (22-10-09)
• topic autologus chondrocyte implantation
• THE ROLE OF AUTOLOGOUS CHONDROCYTE IMPLANTATION (ACI) IN THE TR
• Slide 4
• AUTOLOGOUS CHONDROCYTE GRAFTS MULTICENTRIC TRIAL WITH 28 KNEE
• Slide 6
• Slide 7
• Articular Cartilage
• Hyaline Cartilage Structure 1048715The ldquostuffrdquo of cartilage
• Slide 11
• Cartilage Injury Occurs in Many Forms
• Articular Cartilage Defects a treatment challenge
• AND WHAT IS IN OUR BASKET
• SO IT LED US TO SEARCH OF MORE PROMISING OPTION
• Autologous Chondrocyte Implantation (ACI) BACKGROUND
• Identifying a Carticelreg Patient
• Identifying a Carticelreg Patienthelliphellip
• Pre-requisite for surgery
• Autologous Chondrocyte Implantation (ACI)
• Techniques
• ACIMACI Generic Method
• Slide 23
• Treatment with CARTICEL
• CARTICEL Manufacturing and Delivery
• Step 2 Implantation
• CARTICEL Implantation
• Periosteal Patch
• Slide 29
• Slide 30
• Aci steps summarised
• Slide 32
• Complications
• Slide 34
• Slide 35
• FOLLOW UP Biopsy
• FOLLOW UP MRI
• FOLLOW UP ARTHROSCOPIC
• Rehabilitation guidelines
• ACI Rehabilitation
• ACI Rehabilitation (2)
• COMPARISON WITH OTHER METHODS OF TREATMENTS
• COMPARISON WITH OTHER METHODS OF TREATMENTShelliphelliphellip
• COMPARISON WITH OTHER METHODS OF TREATMENTShelliphelliphellip (2)
• CONCLUSIONS
• Slide 46
• Recent advancesHYAFF 3D matrix
• HYAFF-based Scaffold
• CHONDRONtrade
• RECOVERY TO
• Slide 51

Arthroscopic Debridement

Arthroscopic lavage

Subchondral drilling

Microfracture MARROW STIMULATION TECHNIQUES Abrasion arthroplasty -to induce the growth of fibrocartilage into the chondral defect (This fibrocartilage does not withstand shock or shearing force as well as the original hyaline cartilage and may deteriorate over time)

AND WHAT IS IN OUR BASKET

AUTOLOGUS CHONDROCYTE IMPLANTATION

SO IT LED US TO SEARCH OF MORE PROMISING OPTION

JBJS [Am] 1987 Peterson et al Gothenburgndash first application of cell engineering in orthopaedics

NEJM 1994 Brittberg et al Swedenndash successfuly regenerated hyaline-like cartilage in isolated chondral defects

AUTOLOGOUS CHONDROCYTE IMPLANTATION (ACI) BACKGROUND

IDENTIFYING A CARTICELreg PATIENT

Patient FactorsYounger patients ndash lt age 45 - 50 (avg ~ 35 yo)

Significant impairment-Compromised daily livingactivities -Refractory to treatment

Obesity

Demanding Physical activities

Willing amp capable of rehabilitation program

IDENTIFYING A CARTICELreg PATIENThelliphellip

Joint FactorsSymptomatic cartilage defects -Moderate to large (gt 2cm2 d= 16) -On the distal femur (mfc lfc trochlea) -Average defect size gt 4 cm2

-Either chondral or osteochondral

Relatively healthy joint ndash -No arthritis

Co-morbidities(meniscal tear

instability or malalignment) must be corrected prior or concurrent to implantation

Pre-requisite for surgery

Not recommended for patients who have

Appropriate biomachenical alignment

Ligamentous stabilty

Range of motion

an unstable knee

patients sensitive to materials of bovine origins

allergic to the antibiotic gentamicin

in children

yet in any joint other than the knee

AUTOLOGOUS CHONDROCYTEIMPLANTATION (ACI)

StrengthsCan produce hyaline-like cartilageCan fill defects regardless of size with functional repair tissueModerate to large defects that have failed previous interventionRepair tissue which matures rather than deteriorates over timeExpected outcomeReturn to previous level of functioning

ldquoBiological Joint replacementrdquo

LimitationsMore invasiveExpenseLonger recovery

A ACI ndash Periosteum (cells under periosteum)

B ACI ndash Chondrogide (cells under membrane)

C MACI ndash Matrix Induced ACI (cells on membrane)

Chondrogide Membrane Porcine type IIII Inert Seal Resorbs in 3-4 months

ACI MACI

TECHNIQUES

Under inert collagen membrane (ACI)

On inert collagen membrane (MACI)

Harvest 200-300mg full thickness cartilage from trochlea (non load bearing)

Cells grown on monolayer with patients serum

No cells x 20-30

ACIMACI GENERIC METHOD

ACI METHOD

TREATMENT WITH CARTICEL

Uses your own cartilage cells (chondrocytes) to repair the articular cartilage damage in your knee When implanted into a cartilage injury your own cells can form new cartilage this new cartilage is very similar to your original cartilage The CARTICEL implantation procedure is called Autologous Chondrocyte Implantation or ACI It is a two-step process

Knee Cartilage Arthroscopy and BiopsyDuring an arthroscopic procedure surgeon assesses the extent of cartilage damage amp pt as a candidate for CARTICEL implantation

ldquoBiopsyrdquo of healthy tissue about the size of a pencil eraser ie about 200 -300 mg

From outer edge of sup Med or lat Femoral condyle or inner edge of lat Femoral condyle at the intercondylar notch

This sample is sent to product labs

Step 1 Biopsy

Biopsy can be stored for up to two years so you can schedule your surgery at your convenience

When you are ready your cells are cultured over three to five weeks they increase to approx 12 million cells in a vial containing 03 ndash 04 cc of medium Every step of the manufacturing process is monitored to ensure high quality and safety

CARTICEL MANUFACTURING AND DELIVERY

STEP 2 IMPLANTATION

Cartilage Injury CleanedDuring this second stage arthrotomy done to expose knee and any dead or damaged tissue from the injury removed with curette leaving only healthy tissue

Biomachenical allignment procedures if required should be done in conjunction with implantation

CARTICEL IMPLANTATION

PERIOSTEAL PATCH

surgeon takes a small piece of tissue from your shin bone and sews it securely over the injury

CARTICEL Implantation surgeon injects CARTICEL under the patch

When CARTICEL is surgically implanted into a cartilage injury it can grow and form new hyaline-like cartilage with properties similar to those of the original cartilage

Repairing the injury helps to reduce pain and improve movement and function

ACI STEPS summarised

MACI METHOD

Cultured chondrocytes seeded in bilayered typeIIII collagen membrane

Implanted using fibrin glue

Matrix remodelled in months replaced by extracellular matrix regenerate

The overall failure rate is at present quoted as being 10 The two most common complications include bullloosening of the transplant tissue bullformation of fibrous tissue at the repair site and adhesions with return of pain and locking Neither of these complications usually leaves the patient in a worse condition than hisher pre-transplantation state

Other adverse events include bullpost-op haematoma (big blood clot)bullhypertrophic synovitis (angry knee) and superficial wound infection

COMPLICATIONS

IMPROVEMENTS IN CLINICAL OUTCOME

ASSESMENT OF TECHNIQUE

FOLLOW UP RESULTS

ONE YEAR ASSESSMENT

Radiographs Alignment Bone quality

MRI Healing

cartilage Graft failure

Arthroscopy + probe Graft integrity Pressure biopsy

FOLLOW UP BIOPSY

FOLLOW UP MRI

Final appearance of theperiosteum sutured overfemoral condyle defect Thecartilage cells have beeninjected under the flap and thefinal suture placed to close thecover and provide a watertightseal

FOLLOW UP ARTHROSCOPIC

Arthroscopic appearance of thesame area 12 months afterCarticeltrade implantation Thedefect is no longer visible andthere is now hyaline cartilage(biopsy proven) filling theoriginal defect site

REHABILITATION GUIDELINES

Immobilization first 12-24 hours

(CPM) after 12-24 hours for about 4 weeks

Complete joint loading from about 5th week trochleapatellafrom about 8th week condyle Back to sports Low impact rarr within 6 monthsRepeated impact rarr from 8th monthHigh impact rarr from 10-12th month

ACI REHABILITATION

Weight bearingIt is recommended to keep you in non-weight bearing until the second week after surgery (ACI) You can increase the weight bearing gradually and you may be able to sustain your full weight bearing after 6 to 12 weeks from surgery

Range of motionRecovery on your ROM (Range of Motion) is gradually increased with a continuous passive motion (CPM) machine and may be completed to 140 degrees of ROM at 6 weeks to 12 weeks after surgery

ACI REHABILITATIONIndoor exerciseYou can strenghthen your muscles surrounding the knee joint with a four point exercise as well as isometric hamstring and squatting exercises from 4 weeks to 6 weeks after surgeryYou may start performing stationary bike activity without resistance and increase the resistance gradually

Outdoor exerciseAt 13 weeks after surgery you can start walking lightly and at 10 months after surgery you can perform jogging and then you may enjoy intensity exercise like playing tennis or volleyball from 18 months after surgery

Rehabilitation Goals at 12 weeks after ACIFull ROM (Range of Motion) Minimal edema level Minimal occasional pain Pain free tolerance to transitional phase exercise with adequate stability and motor control

COMPARISON WITH OTHER METHODS OF TREATMENTS

Autologous Chondrocyte Implantation Aims to increase the best condition for cartilage defectAdvantagesbullHyaline cartilage is formed bullPermanent reconstructed cartilage tissue bullMost valuable treatment

bullWith Fourth Generation ACI Use of cell ndash gel mixture (collagen hyaluronic acid and fibrin) has fast gelling properties (1 ndash 5 min) upon transplantation bullNo membrane or periosteal patch bullMinimal surgical exposure and reduced surgery time bullCorrects evenly irregular defect shapes bullApplicable to larger defects

COMPARISON WITH OTHER METHODS OF TREATMENTShelliphelliphellip

Abrasion arthroplastyAims to decrease the inflammation of the jointDisadvantagesbullRemoves many cartilage fragments from the jointbullSymptoms reoccur within one year

Drilling and MicrofractureAims to generate a healing responseDisadvantagesbullThe healing response in inadequate bullNo hyaline cartilage is formed but rather fibrocartilage bullHas a limited lifespan of approximately one year bullRapid deterioration after such procedures can be expected

COMPARISON WITH OTHER METHODS OF TREATMENTShelliphelliphellip

Perichondral ResurfacingDisadvantagesbullIsolated cartilage defects are often too large to be covered byh perichondrum bullLong term follow-up of such procedures indicate that the implants undergo endochondral ossification

Synthetic Materials (ie Carbon Fiber Mesh)Disadvantagesbull It often results in fibrous tissue formation bullNot adequate biomechanically bullOften the cause for synovitis in the joints

Osteocartiloginous GraftsAims to reconstruct jointsDisadvantagesbullUnless fresh cartilage is transplanted the cartilage is dead bullFresh grafts are not commonly used as they inevitably carry a risk of disease transmission bullCyropreserved grafts can survive for many years but ultimately deteriorate

Results of the Carticeltrade procedure have been encouraging although it is not always successful An analysis was done of the US and Swedish registry of 153 consecutive patients undergoing this procedure with follow-up from 1 week to 94 months The following results were obtainedbull Patients with clinical improvement 85bull Good or Excellent results 42 bull Good or Excellent results at 2 yearspersisting at 5 years post-op 97

Thus a total of 85 of patients showed some or complete improvement with theimplantation technique The Carticel procedure demonstrated good durability at 5-10 years out

CONCLUSIONS

CONCLUSIONS ACI Vs MACI No current evidence to justify aggressive treatment of

asymptomatic lesions with ACIMACI

Patients with full thickness symptomatic defects do poorly if left untreated

ACI and MACI lead to significant improvement in objective and patient reported clinical outcome scores for up to ten years(even among those with previous failed marrow stimulation techniques)

MACI has a superior rate of clinical improvement in comparison to ACI

Repair tissue may remodel and improve in quality with time

ACI and MACI comparable at 6 years

RECENT ADVANCESHYAFF 3D MATRIX

HYAFF biomaterialscontain high quantities ofderivatized HA

HA-richchondrocyte compatibleembryonic-like mileuconductive to regenerativehealing patterns

bull Non woven felt 2 mm thick fiber diameter 10 micronsbull Chondrocytes are isolated and passaged in culture on plasticdishes up to 3 weeksbull Cells are seeded for 2 weeks on HYAFF scaffold at a density of1 x 106 cm2 resulting in a total of 4 x 106 cm2 seeded cells pergraft

HYAFF-BASED SCAFFOLD

CHONDRONtrade

Uses a cell ndash gel mixture (includes collagen hyaluronic acid and fibrin) that has fast gelling properties (1 ndash 5 min) upon transplantation

This cell and gel mixture enable even cell distribution three-dimensionally moldable to fit irregular defect shape and applicable to a larger defectThus there is minimal surgical exposure and reduced surgery time

(three-dimensional reconstruction of a chondron from the growth plate of the murine long bone the model was generated from multiple sections imaged in an electron microscope plasma membranes are coloured green and internal organelles are visible within the top cell)

RECOVERY TO

HEALTHY ACTIVE LIFE

THANK YOU

• journal club (22-10-09)
• topic autologus chondrocyte implantation
• THE ROLE OF AUTOLOGOUS CHONDROCYTE IMPLANTATION (ACI) IN THE TR
• Slide 4
• AUTOLOGOUS CHONDROCYTE GRAFTS MULTICENTRIC TRIAL WITH 28 KNEE
• Slide 6
• Slide 7
• Articular Cartilage
• Hyaline Cartilage Structure 1048715The ldquostuffrdquo of cartilage
• Slide 11
• Cartilage Injury Occurs in Many Forms
• Articular Cartilage Defects a treatment challenge
• AND WHAT IS IN OUR BASKET
• SO IT LED US TO SEARCH OF MORE PROMISING OPTION
• Autologous Chondrocyte Implantation (ACI) BACKGROUND
• Identifying a Carticelreg Patient
• Identifying a Carticelreg Patienthelliphellip
• Pre-requisite for surgery
• Autologous Chondrocyte Implantation (ACI)
• Techniques
• ACIMACI Generic Method
• Slide 23
• Treatment with CARTICEL
• CARTICEL Manufacturing and Delivery
• Step 2 Implantation
• CARTICEL Implantation
• Periosteal Patch
• Slide 29
• Slide 30
• Aci steps summarised
• Slide 32
• Complications
• Slide 34
• Slide 35
• FOLLOW UP Biopsy
• FOLLOW UP MRI
• FOLLOW UP ARTHROSCOPIC
• Rehabilitation guidelines
• ACI Rehabilitation
• ACI Rehabilitation (2)
• COMPARISON WITH OTHER METHODS OF TREATMENTS
• COMPARISON WITH OTHER METHODS OF TREATMENTShelliphelliphellip
• COMPARISON WITH OTHER METHODS OF TREATMENTShelliphelliphellip (2)
• CONCLUSIONS
• Slide 46
• Recent advancesHYAFF 3D matrix
• HYAFF-based Scaffold
• CHONDRONtrade
• RECOVERY TO
• Slide 51

AUTOLOGUS CHONDROCYTE IMPLANTATION

SO IT LED US TO SEARCH OF MORE PROMISING OPTION

JBJS [Am] 1987 Peterson et al Gothenburgndash first application of cell engineering in orthopaedics

NEJM 1994 Brittberg et al Swedenndash successfuly regenerated hyaline-like cartilage in isolated chondral defects

AUTOLOGOUS CHONDROCYTE IMPLANTATION (ACI) BACKGROUND

IDENTIFYING A CARTICELreg PATIENT

Patient FactorsYounger patients ndash lt age 45 - 50 (avg ~ 35 yo)

Significant impairment-Compromised daily livingactivities -Refractory to treatment

Obesity

Demanding Physical activities

Willing amp capable of rehabilitation program

IDENTIFYING A CARTICELreg PATIENThelliphellip

Joint FactorsSymptomatic cartilage defects -Moderate to large (gt 2cm2 d= 16) -On the distal femur (mfc lfc trochlea) -Average defect size gt 4 cm2

-Either chondral or osteochondral

Relatively healthy joint ndash -No arthritis

Co-morbidities(meniscal tear

instability or malalignment) must be corrected prior or concurrent to implantation

Pre-requisite for surgery

Not recommended for patients who have

Appropriate biomachenical alignment

Ligamentous stabilty

Range of motion

an unstable knee

patients sensitive to materials of bovine origins

allergic to the antibiotic gentamicin

in children

yet in any joint other than the knee

AUTOLOGOUS CHONDROCYTEIMPLANTATION (ACI)

StrengthsCan produce hyaline-like cartilageCan fill defects regardless of size with functional repair tissueModerate to large defects that have failed previous interventionRepair tissue which matures rather than deteriorates over timeExpected outcomeReturn to previous level of functioning

ldquoBiological Joint replacementrdquo

LimitationsMore invasiveExpenseLonger recovery

A ACI ndash Periosteum (cells under periosteum)

B ACI ndash Chondrogide (cells under membrane)

C MACI ndash Matrix Induced ACI (cells on membrane)

Chondrogide Membrane Porcine type IIII Inert Seal Resorbs in 3-4 months

ACI MACI

TECHNIQUES

Under inert collagen membrane (ACI)

On inert collagen membrane (MACI)

Harvest 200-300mg full thickness cartilage from trochlea (non load bearing)

Cells grown on monolayer with patients serum

No cells x 20-30

ACIMACI GENERIC METHOD

ACI METHOD

TREATMENT WITH CARTICEL

Uses your own cartilage cells (chondrocytes) to repair the articular cartilage damage in your knee When implanted into a cartilage injury your own cells can form new cartilage this new cartilage is very similar to your original cartilage The CARTICEL implantation procedure is called Autologous Chondrocyte Implantation or ACI It is a two-step process

Knee Cartilage Arthroscopy and BiopsyDuring an arthroscopic procedure surgeon assesses the extent of cartilage damage amp pt as a candidate for CARTICEL implantation

ldquoBiopsyrdquo of healthy tissue about the size of a pencil eraser ie about 200 -300 mg

From outer edge of sup Med or lat Femoral condyle or inner edge of lat Femoral condyle at the intercondylar notch

This sample is sent to product labs

Step 1 Biopsy

Biopsy can be stored for up to two years so you can schedule your surgery at your convenience

When you are ready your cells are cultured over three to five weeks they increase to approx 12 million cells in a vial containing 03 ndash 04 cc of medium Every step of the manufacturing process is monitored to ensure high quality and safety

CARTICEL MANUFACTURING AND DELIVERY

STEP 2 IMPLANTATION

Cartilage Injury CleanedDuring this second stage arthrotomy done to expose knee and any dead or damaged tissue from the injury removed with curette leaving only healthy tissue

Biomachenical allignment procedures if required should be done in conjunction with implantation

CARTICEL IMPLANTATION

PERIOSTEAL PATCH

surgeon takes a small piece of tissue from your shin bone and sews it securely over the injury

CARTICEL Implantation surgeon injects CARTICEL under the patch

When CARTICEL is surgically implanted into a cartilage injury it can grow and form new hyaline-like cartilage with properties similar to those of the original cartilage

Repairing the injury helps to reduce pain and improve movement and function

ACI STEPS summarised

MACI METHOD

Cultured chondrocytes seeded in bilayered typeIIII collagen membrane

Implanted using fibrin glue

Matrix remodelled in months replaced by extracellular matrix regenerate

The overall failure rate is at present quoted as being 10 The two most common complications include bullloosening of the transplant tissue bullformation of fibrous tissue at the repair site and adhesions with return of pain and locking Neither of these complications usually leaves the patient in a worse condition than hisher pre-transplantation state

Other adverse events include bullpost-op haematoma (big blood clot)bullhypertrophic synovitis (angry knee) and superficial wound infection

COMPLICATIONS

IMPROVEMENTS IN CLINICAL OUTCOME

ASSESMENT OF TECHNIQUE

FOLLOW UP RESULTS

ONE YEAR ASSESSMENT

Radiographs Alignment Bone quality

MRI Healing

cartilage Graft failure

Arthroscopy + probe Graft integrity Pressure biopsy

FOLLOW UP BIOPSY

FOLLOW UP MRI

Final appearance of theperiosteum sutured overfemoral condyle defect Thecartilage cells have beeninjected under the flap and thefinal suture placed to close thecover and provide a watertightseal

FOLLOW UP ARTHROSCOPIC

Arthroscopic appearance of thesame area 12 months afterCarticeltrade implantation Thedefect is no longer visible andthere is now hyaline cartilage(biopsy proven) filling theoriginal defect site

REHABILITATION GUIDELINES

Immobilization first 12-24 hours

(CPM) after 12-24 hours for about 4 weeks

Complete joint loading from about 5th week trochleapatellafrom about 8th week condyle Back to sports Low impact rarr within 6 monthsRepeated impact rarr from 8th monthHigh impact rarr from 10-12th month

ACI REHABILITATION

Weight bearingIt is recommended to keep you in non-weight bearing until the second week after surgery (ACI) You can increase the weight bearing gradually and you may be able to sustain your full weight bearing after 6 to 12 weeks from surgery

Range of motionRecovery on your ROM (Range of Motion) is gradually increased with a continuous passive motion (CPM) machine and may be completed to 140 degrees of ROM at 6 weeks to 12 weeks after surgery

ACI REHABILITATIONIndoor exerciseYou can strenghthen your muscles surrounding the knee joint with a four point exercise as well as isometric hamstring and squatting exercises from 4 weeks to 6 weeks after surgeryYou may start performing stationary bike activity without resistance and increase the resistance gradually

Outdoor exerciseAt 13 weeks after surgery you can start walking lightly and at 10 months after surgery you can perform jogging and then you may enjoy intensity exercise like playing tennis or volleyball from 18 months after surgery

Rehabilitation Goals at 12 weeks after ACIFull ROM (Range of Motion) Minimal edema level Minimal occasional pain Pain free tolerance to transitional phase exercise with adequate stability and motor control

COMPARISON WITH OTHER METHODS OF TREATMENTS

Autologous Chondrocyte Implantation Aims to increase the best condition for cartilage defectAdvantagesbullHyaline cartilage is formed bullPermanent reconstructed cartilage tissue bullMost valuable treatment

bullWith Fourth Generation ACI Use of cell ndash gel mixture (collagen hyaluronic acid and fibrin) has fast gelling properties (1 ndash 5 min) upon transplantation bullNo membrane or periosteal patch bullMinimal surgical exposure and reduced surgery time bullCorrects evenly irregular defect shapes bullApplicable to larger defects

COMPARISON WITH OTHER METHODS OF TREATMENTShelliphelliphellip

Abrasion arthroplastyAims to decrease the inflammation of the jointDisadvantagesbullRemoves many cartilage fragments from the jointbullSymptoms reoccur within one year

Drilling and MicrofractureAims to generate a healing responseDisadvantagesbullThe healing response in inadequate bullNo hyaline cartilage is formed but rather fibrocartilage bullHas a limited lifespan of approximately one year bullRapid deterioration after such procedures can be expected

COMPARISON WITH OTHER METHODS OF TREATMENTShelliphelliphellip

Perichondral ResurfacingDisadvantagesbullIsolated cartilage defects are often too large to be covered byh perichondrum bullLong term follow-up of such procedures indicate that the implants undergo endochondral ossification

Synthetic Materials (ie Carbon Fiber Mesh)Disadvantagesbull It often results in fibrous tissue formation bullNot adequate biomechanically bullOften the cause for synovitis in the joints

Osteocartiloginous GraftsAims to reconstruct jointsDisadvantagesbullUnless fresh cartilage is transplanted the cartilage is dead bullFresh grafts are not commonly used as they inevitably carry a risk of disease transmission bullCyropreserved grafts can survive for many years but ultimately deteriorate

Results of the Carticeltrade procedure have been encouraging although it is not always successful An analysis was done of the US and Swedish registry of 153 consecutive patients undergoing this procedure with follow-up from 1 week to 94 months The following results were obtainedbull Patients with clinical improvement 85bull Good or Excellent results 42 bull Good or Excellent results at 2 yearspersisting at 5 years post-op 97

Thus a total of 85 of patients showed some or complete improvement with theimplantation technique The Carticel procedure demonstrated good durability at 5-10 years out

CONCLUSIONS

CONCLUSIONS ACI Vs MACI No current evidence to justify aggressive treatment of

asymptomatic lesions with ACIMACI

Patients with full thickness symptomatic defects do poorly if left untreated

ACI and MACI lead to significant improvement in objective and patient reported clinical outcome scores for up to ten years(even among those with previous failed marrow stimulation techniques)

MACI has a superior rate of clinical improvement in comparison to ACI

Repair tissue may remodel and improve in quality with time

ACI and MACI comparable at 6 years

RECENT ADVANCESHYAFF 3D MATRIX

HYAFF biomaterialscontain high quantities ofderivatized HA

HA-richchondrocyte compatibleembryonic-like mileuconductive to regenerativehealing patterns

bull Non woven felt 2 mm thick fiber diameter 10 micronsbull Chondrocytes are isolated and passaged in culture on plasticdishes up to 3 weeksbull Cells are seeded for 2 weeks on HYAFF scaffold at a density of1 x 106 cm2 resulting in a total of 4 x 106 cm2 seeded cells pergraft

HYAFF-BASED SCAFFOLD

CHONDRONtrade

Uses a cell ndash gel mixture (includes collagen hyaluronic acid and fibrin) that has fast gelling properties (1 ndash 5 min) upon transplantation

This cell and gel mixture enable even cell distribution three-dimensionally moldable to fit irregular defect shape and applicable to a larger defectThus there is minimal surgical exposure and reduced surgery time

(three-dimensional reconstruction of a chondron from the growth plate of the murine long bone the model was generated from multiple sections imaged in an electron microscope plasma membranes are coloured green and internal organelles are visible within the top cell)

RECOVERY TO

HEALTHY ACTIVE LIFE

THANK YOU

• journal club (22-10-09)
• topic autologus chondrocyte implantation
• THE ROLE OF AUTOLOGOUS CHONDROCYTE IMPLANTATION (ACI) IN THE TR
• Slide 4
• AUTOLOGOUS CHONDROCYTE GRAFTS MULTICENTRIC TRIAL WITH 28 KNEE
• Slide 6
• Slide 7
• Articular Cartilage
• Hyaline Cartilage Structure 1048715The ldquostuffrdquo of cartilage
• Slide 11
• Cartilage Injury Occurs in Many Forms
• Articular Cartilage Defects a treatment challenge
• AND WHAT IS IN OUR BASKET
• SO IT LED US TO SEARCH OF MORE PROMISING OPTION
• Autologous Chondrocyte Implantation (ACI) BACKGROUND
• Identifying a Carticelreg Patient
• Identifying a Carticelreg Patienthelliphellip
• Pre-requisite for surgery
• Autologous Chondrocyte Implantation (ACI)
• Techniques
• ACIMACI Generic Method
• Slide 23
• Treatment with CARTICEL
• CARTICEL Manufacturing and Delivery
• Step 2 Implantation
• CARTICEL Implantation
• Periosteal Patch
• Slide 29
• Slide 30
• Aci steps summarised
• Slide 32
• Complications
• Slide 34
• Slide 35
• FOLLOW UP Biopsy
• FOLLOW UP MRI
• FOLLOW UP ARTHROSCOPIC
• Rehabilitation guidelines
• ACI Rehabilitation
• ACI Rehabilitation (2)
• COMPARISON WITH OTHER METHODS OF TREATMENTS
• COMPARISON WITH OTHER METHODS OF TREATMENTShelliphelliphellip
• COMPARISON WITH OTHER METHODS OF TREATMENTShelliphelliphellip (2)
• CONCLUSIONS
• Slide 46
• Recent advancesHYAFF 3D matrix
• HYAFF-based Scaffold
• CHONDRONtrade
• RECOVERY TO
• Slide 51

JBJS [Am] 1987 Peterson et al Gothenburgndash first application of cell engineering in orthopaedics

NEJM 1994 Brittberg et al Swedenndash successfuly regenerated hyaline-like cartilage in isolated chondral defects

AUTOLOGOUS CHONDROCYTE IMPLANTATION (ACI) BACKGROUND

IDENTIFYING A CARTICELreg PATIENT

Patient FactorsYounger patients ndash lt age 45 - 50 (avg ~ 35 yo)

Significant impairment-Compromised daily livingactivities -Refractory to treatment

Obesity

Demanding Physical activities

Willing amp capable of rehabilitation program

IDENTIFYING A CARTICELreg PATIENThelliphellip

Joint FactorsSymptomatic cartilage defects -Moderate to large (gt 2cm2 d= 16) -On the distal femur (mfc lfc trochlea) -Average defect size gt 4 cm2

-Either chondral or osteochondral

Relatively healthy joint ndash -No arthritis

Co-morbidities(meniscal tear

instability or malalignment) must be corrected prior or concurrent to implantation

Pre-requisite for surgery

Not recommended for patients who have

Appropriate biomachenical alignment

Ligamentous stabilty

Range of motion

an unstable knee

patients sensitive to materials of bovine origins

allergic to the antibiotic gentamicin

in children

yet in any joint other than the knee

AUTOLOGOUS CHONDROCYTEIMPLANTATION (ACI)

StrengthsCan produce hyaline-like cartilageCan fill defects regardless of size with functional repair tissueModerate to large defects that have failed previous interventionRepair tissue which matures rather than deteriorates over timeExpected outcomeReturn to previous level of functioning

ldquoBiological Joint replacementrdquo

LimitationsMore invasiveExpenseLonger recovery

A ACI ndash Periosteum (cells under periosteum)

B ACI ndash Chondrogide (cells under membrane)

C MACI ndash Matrix Induced ACI (cells on membrane)

Chondrogide Membrane Porcine type IIII Inert Seal Resorbs in 3-4 months

ACI MACI

TECHNIQUES

Under inert collagen membrane (ACI)

On inert collagen membrane (MACI)

Harvest 200-300mg full thickness cartilage from trochlea (non load bearing)

Cells grown on monolayer with patients serum

No cells x 20-30

ACIMACI GENERIC METHOD

ACI METHOD

TREATMENT WITH CARTICEL

Uses your own cartilage cells (chondrocytes) to repair the articular cartilage damage in your knee When implanted into a cartilage injury your own cells can form new cartilage this new cartilage is very similar to your original cartilage The CARTICEL implantation procedure is called Autologous Chondrocyte Implantation or ACI It is a two-step process

Knee Cartilage Arthroscopy and BiopsyDuring an arthroscopic procedure surgeon assesses the extent of cartilage damage amp pt as a candidate for CARTICEL implantation

ldquoBiopsyrdquo of healthy tissue about the size of a pencil eraser ie about 200 -300 mg

From outer edge of sup Med or lat Femoral condyle or inner edge of lat Femoral condyle at the intercondylar notch

This sample is sent to product labs

Step 1 Biopsy

Biopsy can be stored for up to two years so you can schedule your surgery at your convenience

When you are ready your cells are cultured over three to five weeks they increase to approx 12 million cells in a vial containing 03 ndash 04 cc of medium Every step of the manufacturing process is monitored to ensure high quality and safety

CARTICEL MANUFACTURING AND DELIVERY

STEP 2 IMPLANTATION

Cartilage Injury CleanedDuring this second stage arthrotomy done to expose knee and any dead or damaged tissue from the injury removed with curette leaving only healthy tissue

Biomachenical allignment procedures if required should be done in conjunction with implantation

CARTICEL IMPLANTATION

PERIOSTEAL PATCH

surgeon takes a small piece of tissue from your shin bone and sews it securely over the injury

CARTICEL Implantation surgeon injects CARTICEL under the patch

When CARTICEL is surgically implanted into a cartilage injury it can grow and form new hyaline-like cartilage with properties similar to those of the original cartilage

Repairing the injury helps to reduce pain and improve movement and function

ACI STEPS summarised

MACI METHOD

Cultured chondrocytes seeded in bilayered typeIIII collagen membrane

Implanted using fibrin glue

Matrix remodelled in months replaced by extracellular matrix regenerate

The overall failure rate is at present quoted as being 10 The two most common complications include bullloosening of the transplant tissue bullformation of fibrous tissue at the repair site and adhesions with return of pain and locking Neither of these complications usually leaves the patient in a worse condition than hisher pre-transplantation state

Other adverse events include bullpost-op haematoma (big blood clot)bullhypertrophic synovitis (angry knee) and superficial wound infection

COMPLICATIONS

IMPROVEMENTS IN CLINICAL OUTCOME

ASSESMENT OF TECHNIQUE

FOLLOW UP RESULTS

ONE YEAR ASSESSMENT

Radiographs Alignment Bone quality

MRI Healing

cartilage Graft failure

Arthroscopy + probe Graft integrity Pressure biopsy

FOLLOW UP BIOPSY

FOLLOW UP MRI

Final appearance of theperiosteum sutured overfemoral condyle defect Thecartilage cells have beeninjected under the flap and thefinal suture placed to close thecover and provide a watertightseal

FOLLOW UP ARTHROSCOPIC

Arthroscopic appearance of thesame area 12 months afterCarticeltrade implantation Thedefect is no longer visible andthere is now hyaline cartilage(biopsy proven) filling theoriginal defect site

REHABILITATION GUIDELINES

Immobilization first 12-24 hours

(CPM) after 12-24 hours for about 4 weeks

Complete joint loading from about 5th week trochleapatellafrom about 8th week condyle Back to sports Low impact rarr within 6 monthsRepeated impact rarr from 8th monthHigh impact rarr from 10-12th month

ACI REHABILITATION

Weight bearingIt is recommended to keep you in non-weight bearing until the second week after surgery (ACI) You can increase the weight bearing gradually and you may be able to sustain your full weight bearing after 6 to 12 weeks from surgery

Range of motionRecovery on your ROM (Range of Motion) is gradually increased with a continuous passive motion (CPM) machine and may be completed to 140 degrees of ROM at 6 weeks to 12 weeks after surgery

ACI REHABILITATIONIndoor exerciseYou can strenghthen your muscles surrounding the knee joint with a four point exercise as well as isometric hamstring and squatting exercises from 4 weeks to 6 weeks after surgeryYou may start performing stationary bike activity without resistance and increase the resistance gradually

Outdoor exerciseAt 13 weeks after surgery you can start walking lightly and at 10 months after surgery you can perform jogging and then you may enjoy intensity exercise like playing tennis or volleyball from 18 months after surgery

Rehabilitation Goals at 12 weeks after ACIFull ROM (Range of Motion) Minimal edema level Minimal occasional pain Pain free tolerance to transitional phase exercise with adequate stability and motor control

COMPARISON WITH OTHER METHODS OF TREATMENTS

Autologous Chondrocyte Implantation Aims to increase the best condition for cartilage defectAdvantagesbullHyaline cartilage is formed bullPermanent reconstructed cartilage tissue bullMost valuable treatment

bullWith Fourth Generation ACI Use of cell ndash gel mixture (collagen hyaluronic acid and fibrin) has fast gelling properties (1 ndash 5 min) upon transplantation bullNo membrane or periosteal patch bullMinimal surgical exposure and reduced surgery time bullCorrects evenly irregular defect shapes bullApplicable to larger defects

COMPARISON WITH OTHER METHODS OF TREATMENTShelliphelliphellip

Abrasion arthroplastyAims to decrease the inflammation of the jointDisadvantagesbullRemoves many cartilage fragments from the jointbullSymptoms reoccur within one year

Drilling and MicrofractureAims to generate a healing responseDisadvantagesbullThe healing response in inadequate bullNo hyaline cartilage is formed but rather fibrocartilage bullHas a limited lifespan of approximately one year bullRapid deterioration after such procedures can be expected

COMPARISON WITH OTHER METHODS OF TREATMENTShelliphelliphellip

Perichondral ResurfacingDisadvantagesbullIsolated cartilage defects are often too large to be covered byh perichondrum bullLong term follow-up of such procedures indicate that the implants undergo endochondral ossification

Synthetic Materials (ie Carbon Fiber Mesh)Disadvantagesbull It often results in fibrous tissue formation bullNot adequate biomechanically bullOften the cause for synovitis in the joints

Osteocartiloginous GraftsAims to reconstruct jointsDisadvantagesbullUnless fresh cartilage is transplanted the cartilage is dead bullFresh grafts are not commonly used as they inevitably carry a risk of disease transmission bullCyropreserved grafts can survive for many years but ultimately deteriorate

Results of the Carticeltrade procedure have been encouraging although it is not always successful An analysis was done of the US and Swedish registry of 153 consecutive patients undergoing this procedure with follow-up from 1 week to 94 months The following results were obtainedbull Patients with clinical improvement 85bull Good or Excellent results 42 bull Good or Excellent results at 2 yearspersisting at 5 years post-op 97

Thus a total of 85 of patients showed some or complete improvement with theimplantation technique The Carticel procedure demonstrated good durability at 5-10 years out

CONCLUSIONS

CONCLUSIONS ACI Vs MACI No current evidence to justify aggressive treatment of

asymptomatic lesions with ACIMACI

Patients with full thickness symptomatic defects do poorly if left untreated

ACI and MACI lead to significant improvement in objective and patient reported clinical outcome scores for up to ten years(even among those with previous failed marrow stimulation techniques)

MACI has a superior rate of clinical improvement in comparison to ACI

Repair tissue may remodel and improve in quality with time

ACI and MACI comparable at 6 years

RECENT ADVANCESHYAFF 3D MATRIX

HYAFF biomaterialscontain high quantities ofderivatized HA

HA-richchondrocyte compatibleembryonic-like mileuconductive to regenerativehealing patterns

bull Non woven felt 2 mm thick fiber diameter 10 micronsbull Chondrocytes are isolated and passaged in culture on plasticdishes up to 3 weeksbull Cells are seeded for 2 weeks on HYAFF scaffold at a density of1 x 106 cm2 resulting in a total of 4 x 106 cm2 seeded cells pergraft

HYAFF-BASED SCAFFOLD

CHONDRONtrade

Uses a cell ndash gel mixture (includes collagen hyaluronic acid and fibrin) that has fast gelling properties (1 ndash 5 min) upon transplantation

This cell and gel mixture enable even cell distribution three-dimensionally moldable to fit irregular defect shape and applicable to a larger defectThus there is minimal surgical exposure and reduced surgery time

(three-dimensional reconstruction of a chondron from the growth plate of the murine long bone the model was generated from multiple sections imaged in an electron microscope plasma membranes are coloured green and internal organelles are visible within the top cell)

RECOVERY TO

HEALTHY ACTIVE LIFE

THANK YOU

• journal club (22-10-09)
• topic autologus chondrocyte implantation
• THE ROLE OF AUTOLOGOUS CHONDROCYTE IMPLANTATION (ACI) IN THE TR
• Slide 4
• AUTOLOGOUS CHONDROCYTE GRAFTS MULTICENTRIC TRIAL WITH 28 KNEE
• Slide 6
• Slide 7
• Articular Cartilage
• Hyaline Cartilage Structure 1048715The ldquostuffrdquo of cartilage
• Slide 11
• Cartilage Injury Occurs in Many Forms
• Articular Cartilage Defects a treatment challenge
• AND WHAT IS IN OUR BASKET
• SO IT LED US TO SEARCH OF MORE PROMISING OPTION
• Autologous Chondrocyte Implantation (ACI) BACKGROUND
• Identifying a Carticelreg Patient
• Identifying a Carticelreg Patienthelliphellip
• Pre-requisite for surgery
• Autologous Chondrocyte Implantation (ACI)
• Techniques
• ACIMACI Generic Method
• Slide 23
• Treatment with CARTICEL
• CARTICEL Manufacturing and Delivery
• Step 2 Implantation
• CARTICEL Implantation
• Periosteal Patch
• Slide 29
• Slide 30
• Aci steps summarised
• Slide 32
• Complications
• Slide 34
• Slide 35
• FOLLOW UP Biopsy
• FOLLOW UP MRI
• FOLLOW UP ARTHROSCOPIC
• Rehabilitation guidelines
• ACI Rehabilitation
• ACI Rehabilitation (2)
• COMPARISON WITH OTHER METHODS OF TREATMENTS
• COMPARISON WITH OTHER METHODS OF TREATMENTShelliphelliphellip
• COMPARISON WITH OTHER METHODS OF TREATMENTShelliphelliphellip (2)
• CONCLUSIONS
• Slide 46
• Recent advancesHYAFF 3D matrix
• HYAFF-based Scaffold
• CHONDRONtrade
• RECOVERY TO
• Slide 51

IDENTIFYING A CARTICELreg PATIENT

Patient FactorsYounger patients ndash lt age 45 - 50 (avg ~ 35 yo)

Significant impairment-Compromised daily livingactivities -Refractory to treatment

Obesity

Demanding Physical activities

Willing amp capable of rehabilitation program

IDENTIFYING A CARTICELreg PATIENThelliphellip

Joint FactorsSymptomatic cartilage defects -Moderate to large (gt 2cm2 d= 16) -On the distal femur (mfc lfc trochlea) -Average defect size gt 4 cm2

-Either chondral or osteochondral

Relatively healthy joint ndash -No arthritis

Co-morbidities(meniscal tear

instability or malalignment) must be corrected prior or concurrent to implantation

Pre-requisite for surgery

Not recommended for patients who have

Appropriate biomachenical alignment

Ligamentous stabilty

Range of motion

an unstable knee

patients sensitive to materials of bovine origins

allergic to the antibiotic gentamicin

in children

yet in any joint other than the knee

AUTOLOGOUS CHONDROCYTEIMPLANTATION (ACI)

StrengthsCan produce hyaline-like cartilageCan fill defects regardless of size with functional repair tissueModerate to large defects that have failed previous interventionRepair tissue which matures rather than deteriorates over timeExpected outcomeReturn to previous level of functioning

ldquoBiological Joint replacementrdquo

LimitationsMore invasiveExpenseLonger recovery

A ACI ndash Periosteum (cells under periosteum)

B ACI ndash Chondrogide (cells under membrane)

C MACI ndash Matrix Induced ACI (cells on membrane)

Chondrogide Membrane Porcine type IIII Inert Seal Resorbs in 3-4 months

ACI MACI

TECHNIQUES

Under inert collagen membrane (ACI)

On inert collagen membrane (MACI)

Harvest 200-300mg full thickness cartilage from trochlea (non load bearing)

Cells grown on monolayer with patients serum

No cells x 20-30

ACIMACI GENERIC METHOD

ACI METHOD

TREATMENT WITH CARTICEL

Uses your own cartilage cells (chondrocytes) to repair the articular cartilage damage in your knee When implanted into a cartilage injury your own cells can form new cartilage this new cartilage is very similar to your original cartilage The CARTICEL implantation procedure is called Autologous Chondrocyte Implantation or ACI It is a two-step process

Knee Cartilage Arthroscopy and BiopsyDuring an arthroscopic procedure surgeon assesses the extent of cartilage damage amp pt as a candidate for CARTICEL implantation

ldquoBiopsyrdquo of healthy tissue about the size of a pencil eraser ie about 200 -300 mg

From outer edge of sup Med or lat Femoral condyle or inner edge of lat Femoral condyle at the intercondylar notch

This sample is sent to product labs

Step 1 Biopsy

Biopsy can be stored for up to two years so you can schedule your surgery at your convenience

When you are ready your cells are cultured over three to five weeks they increase to approx 12 million cells in a vial containing 03 ndash 04 cc of medium Every step of the manufacturing process is monitored to ensure high quality and safety

CARTICEL MANUFACTURING AND DELIVERY

STEP 2 IMPLANTATION

Cartilage Injury CleanedDuring this second stage arthrotomy done to expose knee and any dead or damaged tissue from the injury removed with curette leaving only healthy tissue

Biomachenical allignment procedures if required should be done in conjunction with implantation

CARTICEL IMPLANTATION

PERIOSTEAL PATCH

surgeon takes a small piece of tissue from your shin bone and sews it securely over the injury

CARTICEL Implantation surgeon injects CARTICEL under the patch

When CARTICEL is surgically implanted into a cartilage injury it can grow and form new hyaline-like cartilage with properties similar to those of the original cartilage

Repairing the injury helps to reduce pain and improve movement and function

ACI STEPS summarised

MACI METHOD

Cultured chondrocytes seeded in bilayered typeIIII collagen membrane

Implanted using fibrin glue

Matrix remodelled in months replaced by extracellular matrix regenerate

The overall failure rate is at present quoted as being 10 The two most common complications include bullloosening of the transplant tissue bullformation of fibrous tissue at the repair site and adhesions with return of pain and locking Neither of these complications usually leaves the patient in a worse condition than hisher pre-transplantation state

Other adverse events include bullpost-op haematoma (big blood clot)bullhypertrophic synovitis (angry knee) and superficial wound infection

COMPLICATIONS

IMPROVEMENTS IN CLINICAL OUTCOME

ASSESMENT OF TECHNIQUE

FOLLOW UP RESULTS

ONE YEAR ASSESSMENT

Radiographs Alignment Bone quality

MRI Healing

cartilage Graft failure

Arthroscopy + probe Graft integrity Pressure biopsy

FOLLOW UP BIOPSY

FOLLOW UP MRI

Final appearance of theperiosteum sutured overfemoral condyle defect Thecartilage cells have beeninjected under the flap and thefinal suture placed to close thecover and provide a watertightseal

FOLLOW UP ARTHROSCOPIC

Arthroscopic appearance of thesame area 12 months afterCarticeltrade implantation Thedefect is no longer visible andthere is now hyaline cartilage(biopsy proven) filling theoriginal defect site

REHABILITATION GUIDELINES

Immobilization first 12-24 hours

(CPM) after 12-24 hours for about 4 weeks

Complete joint loading from about 5th week trochleapatellafrom about 8th week condyle Back to sports Low impact rarr within 6 monthsRepeated impact rarr from 8th monthHigh impact rarr from 10-12th month

ACI REHABILITATION

Weight bearingIt is recommended to keep you in non-weight bearing until the second week after surgery (ACI) You can increase the weight bearing gradually and you may be able to sustain your full weight bearing after 6 to 12 weeks from surgery

Range of motionRecovery on your ROM (Range of Motion) is gradually increased with a continuous passive motion (CPM) machine and may be completed to 140 degrees of ROM at 6 weeks to 12 weeks after surgery

ACI REHABILITATIONIndoor exerciseYou can strenghthen your muscles surrounding the knee joint with a four point exercise as well as isometric hamstring and squatting exercises from 4 weeks to 6 weeks after surgeryYou may start performing stationary bike activity without resistance and increase the resistance gradually

Outdoor exerciseAt 13 weeks after surgery you can start walking lightly and at 10 months after surgery you can perform jogging and then you may enjoy intensity exercise like playing tennis or volleyball from 18 months after surgery

Rehabilitation Goals at 12 weeks after ACIFull ROM (Range of Motion) Minimal edema level Minimal occasional pain Pain free tolerance to transitional phase exercise with adequate stability and motor control

COMPARISON WITH OTHER METHODS OF TREATMENTS

Autologous Chondrocyte Implantation Aims to increase the best condition for cartilage defectAdvantagesbullHyaline cartilage is formed bullPermanent reconstructed cartilage tissue bullMost valuable treatment

bullWith Fourth Generation ACI Use of cell ndash gel mixture (collagen hyaluronic acid and fibrin) has fast gelling properties (1 ndash 5 min) upon transplantation bullNo membrane or periosteal patch bullMinimal surgical exposure and reduced surgery time bullCorrects evenly irregular defect shapes bullApplicable to larger defects

COMPARISON WITH OTHER METHODS OF TREATMENTShelliphelliphellip

Abrasion arthroplastyAims to decrease the inflammation of the jointDisadvantagesbullRemoves many cartilage fragments from the jointbullSymptoms reoccur within one year

Drilling and MicrofractureAims to generate a healing responseDisadvantagesbullThe healing response in inadequate bullNo hyaline cartilage is formed but rather fibrocartilage bullHas a limited lifespan of approximately one year bullRapid deterioration after such procedures can be expected

COMPARISON WITH OTHER METHODS OF TREATMENTShelliphelliphellip

Perichondral ResurfacingDisadvantagesbullIsolated cartilage defects are often too large to be covered byh perichondrum bullLong term follow-up of such procedures indicate that the implants undergo endochondral ossification

Synthetic Materials (ie Carbon Fiber Mesh)Disadvantagesbull It often results in fibrous tissue formation bullNot adequate biomechanically bullOften the cause for synovitis in the joints

Osteocartiloginous GraftsAims to reconstruct jointsDisadvantagesbullUnless fresh cartilage is transplanted the cartilage is dead bullFresh grafts are not commonly used as they inevitably carry a risk of disease transmission bullCyropreserved grafts can survive for many years but ultimately deteriorate

Results of the Carticeltrade procedure have been encouraging although it is not always successful An analysis was done of the US and Swedish registry of 153 consecutive patients undergoing this procedure with follow-up from 1 week to 94 months The following results were obtainedbull Patients with clinical improvement 85bull Good or Excellent results 42 bull Good or Excellent results at 2 yearspersisting at 5 years post-op 97

Thus a total of 85 of patients showed some or complete improvement with theimplantation technique The Carticel procedure demonstrated good durability at 5-10 years out

CONCLUSIONS

CONCLUSIONS ACI Vs MACI No current evidence to justify aggressive treatment of

asymptomatic lesions with ACIMACI

Patients with full thickness symptomatic defects do poorly if left untreated

ACI and MACI lead to significant improvement in objective and patient reported clinical outcome scores for up to ten years(even among those with previous failed marrow stimulation techniques)

MACI has a superior rate of clinical improvement in comparison to ACI

Repair tissue may remodel and improve in quality with time

ACI and MACI comparable at 6 years

RECENT ADVANCESHYAFF 3D MATRIX

HYAFF biomaterialscontain high quantities ofderivatized HA

HA-richchondrocyte compatibleembryonic-like mileuconductive to regenerativehealing patterns

bull Non woven felt 2 mm thick fiber diameter 10 micronsbull Chondrocytes are isolated and passaged in culture on plasticdishes up to 3 weeksbull Cells are seeded for 2 weeks on HYAFF scaffold at a density of1 x 106 cm2 resulting in a total of 4 x 106 cm2 seeded cells pergraft

HYAFF-BASED SCAFFOLD

CHONDRONtrade

Uses a cell ndash gel mixture (includes collagen hyaluronic acid and fibrin) that has fast gelling properties (1 ndash 5 min) upon transplantation

This cell and gel mixture enable even cell distribution three-dimensionally moldable to fit irregular defect shape and applicable to a larger defectThus there is minimal surgical exposure and reduced surgery time

(three-dimensional reconstruction of a chondron from the growth plate of the murine long bone the model was generated from multiple sections imaged in an electron microscope plasma membranes are coloured green and internal organelles are visible within the top cell)

RECOVERY TO

HEALTHY ACTIVE LIFE

THANK YOU

• journal club (22-10-09)
• topic autologus chondrocyte implantation
• THE ROLE OF AUTOLOGOUS CHONDROCYTE IMPLANTATION (ACI) IN THE TR
• Slide 4
• AUTOLOGOUS CHONDROCYTE GRAFTS MULTICENTRIC TRIAL WITH 28 KNEE
• Slide 6
• Slide 7
• Articular Cartilage
• Hyaline Cartilage Structure 1048715The ldquostuffrdquo of cartilage
• Slide 11
• Cartilage Injury Occurs in Many Forms
• Articular Cartilage Defects a treatment challenge
• AND WHAT IS IN OUR BASKET
• SO IT LED US TO SEARCH OF MORE PROMISING OPTION
• Autologous Chondrocyte Implantation (ACI) BACKGROUND
• Identifying a Carticelreg Patient
• Identifying a Carticelreg Patienthelliphellip
• Pre-requisite for surgery
• Autologous Chondrocyte Implantation (ACI)
• Techniques
• ACIMACI Generic Method
• Slide 23
• Treatment with CARTICEL
• CARTICEL Manufacturing and Delivery
• Step 2 Implantation
• CARTICEL Implantation
• Periosteal Patch
• Slide 29
• Slide 30
• Aci steps summarised
• Slide 32
• Complications
• Slide 34
• Slide 35
• FOLLOW UP Biopsy
• FOLLOW UP MRI
• FOLLOW UP ARTHROSCOPIC
• Rehabilitation guidelines
• ACI Rehabilitation
• ACI Rehabilitation (2)
• COMPARISON WITH OTHER METHODS OF TREATMENTS
• COMPARISON WITH OTHER METHODS OF TREATMENTShelliphelliphellip
• COMPARISON WITH OTHER METHODS OF TREATMENTShelliphelliphellip (2)
• CONCLUSIONS
• Slide 46
• Recent advancesHYAFF 3D matrix
• HYAFF-based Scaffold
• CHONDRONtrade
• RECOVERY TO
• Slide 51

IDENTIFYING A CARTICELreg PATIENThelliphellip

Joint FactorsSymptomatic cartilage defects -Moderate to large (gt 2cm2 d= 16) -On the distal femur (mfc lfc trochlea) -Average defect size gt 4 cm2

-Either chondral or osteochondral

Relatively healthy joint ndash -No arthritis

Co-morbidities(meniscal tear

instability or malalignment) must be corrected prior or concurrent to implantation

Pre-requisite for surgery

Not recommended for patients who have

Appropriate biomachenical alignment

Ligamentous stabilty

Range of motion

an unstable knee

patients sensitive to materials of bovine origins

allergic to the antibiotic gentamicin

in children

yet in any joint other than the knee

AUTOLOGOUS CHONDROCYTEIMPLANTATION (ACI)

StrengthsCan produce hyaline-like cartilageCan fill defects regardless of size with functional repair tissueModerate to large defects that have failed previous interventionRepair tissue which matures rather than deteriorates over timeExpected outcomeReturn to previous level of functioning

ldquoBiological Joint replacementrdquo

LimitationsMore invasiveExpenseLonger recovery

A ACI ndash Periosteum (cells under periosteum)

B ACI ndash Chondrogide (cells under membrane)

C MACI ndash Matrix Induced ACI (cells on membrane)

Chondrogide Membrane Porcine type IIII Inert Seal Resorbs in 3-4 months

ACI MACI

TECHNIQUES

Under inert collagen membrane (ACI)

On inert collagen membrane (MACI)

Harvest 200-300mg full thickness cartilage from trochlea (non load bearing)

Cells grown on monolayer with patients serum

No cells x 20-30

ACIMACI GENERIC METHOD

ACI METHOD

TREATMENT WITH CARTICEL

Uses your own cartilage cells (chondrocytes) to repair the articular cartilage damage in your knee When implanted into a cartilage injury your own cells can form new cartilage this new cartilage is very similar to your original cartilage The CARTICEL implantation procedure is called Autologous Chondrocyte Implantation or ACI It is a two-step process

Knee Cartilage Arthroscopy and BiopsyDuring an arthroscopic procedure surgeon assesses the extent of cartilage damage amp pt as a candidate for CARTICEL implantation

ldquoBiopsyrdquo of healthy tissue about the size of a pencil eraser ie about 200 -300 mg

From outer edge of sup Med or lat Femoral condyle or inner edge of lat Femoral condyle at the intercondylar notch

This sample is sent to product labs

Step 1 Biopsy

Biopsy can be stored for up to two years so you can schedule your surgery at your convenience

When you are ready your cells are cultured over three to five weeks they increase to approx 12 million cells in a vial containing 03 ndash 04 cc of medium Every step of the manufacturing process is monitored to ensure high quality and safety

CARTICEL MANUFACTURING AND DELIVERY

STEP 2 IMPLANTATION

Cartilage Injury CleanedDuring this second stage arthrotomy done to expose knee and any dead or damaged tissue from the injury removed with curette leaving only healthy tissue

Biomachenical allignment procedures if required should be done in conjunction with implantation

CARTICEL IMPLANTATION

PERIOSTEAL PATCH

surgeon takes a small piece of tissue from your shin bone and sews it securely over the injury

CARTICEL Implantation surgeon injects CARTICEL under the patch

When CARTICEL is surgically implanted into a cartilage injury it can grow and form new hyaline-like cartilage with properties similar to those of the original cartilage

Repairing the injury helps to reduce pain and improve movement and function

ACI STEPS summarised

MACI METHOD

Cultured chondrocytes seeded in bilayered typeIIII collagen membrane

Implanted using fibrin glue

Matrix remodelled in months replaced by extracellular matrix regenerate

The overall failure rate is at present quoted as being 10 The two most common complications include bullloosening of the transplant tissue bullformation of fibrous tissue at the repair site and adhesions with return of pain and locking Neither of these complications usually leaves the patient in a worse condition than hisher pre-transplantation state

Other adverse events include bullpost-op haematoma (big blood clot)bullhypertrophic synovitis (angry knee) and superficial wound infection

COMPLICATIONS

IMPROVEMENTS IN CLINICAL OUTCOME

ASSESMENT OF TECHNIQUE

FOLLOW UP RESULTS

ONE YEAR ASSESSMENT

Radiographs Alignment Bone quality

MRI Healing

cartilage Graft failure

Arthroscopy + probe Graft integrity Pressure biopsy

FOLLOW UP BIOPSY

FOLLOW UP MRI

Final appearance of theperiosteum sutured overfemoral condyle defect Thecartilage cells have beeninjected under the flap and thefinal suture placed to close thecover and provide a watertightseal

FOLLOW UP ARTHROSCOPIC

Arthroscopic appearance of thesame area 12 months afterCarticeltrade implantation Thedefect is no longer visible andthere is now hyaline cartilage(biopsy proven) filling theoriginal defect site

REHABILITATION GUIDELINES

Immobilization first 12-24 hours

(CPM) after 12-24 hours for about 4 weeks

Complete joint loading from about 5th week trochleapatellafrom about 8th week condyle Back to sports Low impact rarr within 6 monthsRepeated impact rarr from 8th monthHigh impact rarr from 10-12th month

ACI REHABILITATION

Weight bearingIt is recommended to keep you in non-weight bearing until the second week after surgery (ACI) You can increase the weight bearing gradually and you may be able to sustain your full weight bearing after 6 to 12 weeks from surgery

Range of motionRecovery on your ROM (Range of Motion) is gradually increased with a continuous passive motion (CPM) machine and may be completed to 140 degrees of ROM at 6 weeks to 12 weeks after surgery

ACI REHABILITATIONIndoor exerciseYou can strenghthen your muscles surrounding the knee joint with a four point exercise as well as isometric hamstring and squatting exercises from 4 weeks to 6 weeks after surgeryYou may start performing stationary bike activity without resistance and increase the resistance gradually

Outdoor exerciseAt 13 weeks after surgery you can start walking lightly and at 10 months after surgery you can perform jogging and then you may enjoy intensity exercise like playing tennis or volleyball from 18 months after surgery

Rehabilitation Goals at 12 weeks after ACIFull ROM (Range of Motion) Minimal edema level Minimal occasional pain Pain free tolerance to transitional phase exercise with adequate stability and motor control

COMPARISON WITH OTHER METHODS OF TREATMENTS

Autologous Chondrocyte Implantation Aims to increase the best condition for cartilage defectAdvantagesbullHyaline cartilage is formed bullPermanent reconstructed cartilage tissue bullMost valuable treatment

bullWith Fourth Generation ACI Use of cell ndash gel mixture (collagen hyaluronic acid and fibrin) has fast gelling properties (1 ndash 5 min) upon transplantation bullNo membrane or periosteal patch bullMinimal surgical exposure and reduced surgery time bullCorrects evenly irregular defect shapes bullApplicable to larger defects

COMPARISON WITH OTHER METHODS OF TREATMENTShelliphelliphellip

Abrasion arthroplastyAims to decrease the inflammation of the jointDisadvantagesbullRemoves many cartilage fragments from the jointbullSymptoms reoccur within one year

Drilling and MicrofractureAims to generate a healing responseDisadvantagesbullThe healing response in inadequate bullNo hyaline cartilage is formed but rather fibrocartilage bullHas a limited lifespan of approximately one year bullRapid deterioration after such procedures can be expected

COMPARISON WITH OTHER METHODS OF TREATMENTShelliphelliphellip

Perichondral ResurfacingDisadvantagesbullIsolated cartilage defects are often too large to be covered byh perichondrum bullLong term follow-up of such procedures indicate that the implants undergo endochondral ossification

Synthetic Materials (ie Carbon Fiber Mesh)Disadvantagesbull It often results in fibrous tissue formation bullNot adequate biomechanically bullOften the cause for synovitis in the joints

Osteocartiloginous GraftsAims to reconstruct jointsDisadvantagesbullUnless fresh cartilage is transplanted the cartilage is dead bullFresh grafts are not commonly used as they inevitably carry a risk of disease transmission bullCyropreserved grafts can survive for many years but ultimately deteriorate

Results of the Carticeltrade procedure have been encouraging although it is not always successful An analysis was done of the US and Swedish registry of 153 consecutive patients undergoing this procedure with follow-up from 1 week to 94 months The following results were obtainedbull Patients with clinical improvement 85bull Good or Excellent results 42 bull Good or Excellent results at 2 yearspersisting at 5 years post-op 97

Thus a total of 85 of patients showed some or complete improvement with theimplantation technique The Carticel procedure demonstrated good durability at 5-10 years out

CONCLUSIONS

CONCLUSIONS ACI Vs MACI No current evidence to justify aggressive treatment of

asymptomatic lesions with ACIMACI

Patients with full thickness symptomatic defects do poorly if left untreated

ACI and MACI lead to significant improvement in objective and patient reported clinical outcome scores for up to ten years(even among those with previous failed marrow stimulation techniques)

MACI has a superior rate of clinical improvement in comparison to ACI

Repair tissue may remodel and improve in quality with time

ACI and MACI comparable at 6 years

RECENT ADVANCESHYAFF 3D MATRIX

HYAFF biomaterialscontain high quantities ofderivatized HA

HA-richchondrocyte compatibleembryonic-like mileuconductive to regenerativehealing patterns

bull Non woven felt 2 mm thick fiber diameter 10 micronsbull Chondrocytes are isolated and passaged in culture on plasticdishes up to 3 weeksbull Cells are seeded for 2 weeks on HYAFF scaffold at a density of1 x 106 cm2 resulting in a total of 4 x 106 cm2 seeded cells pergraft

HYAFF-BASED SCAFFOLD

CHONDRONtrade

Uses a cell ndash gel mixture (includes collagen hyaluronic acid and fibrin) that has fast gelling properties (1 ndash 5 min) upon transplantation

This cell and gel mixture enable even cell distribution three-dimensionally moldable to fit irregular defect shape and applicable to a larger defectThus there is minimal surgical exposure and reduced surgery time

(three-dimensional reconstruction of a chondron from the growth plate of the murine long bone the model was generated from multiple sections imaged in an electron microscope plasma membranes are coloured green and internal organelles are visible within the top cell)

RECOVERY TO

HEALTHY ACTIVE LIFE

THANK YOU

• journal club (22-10-09)
• topic autologus chondrocyte implantation
• THE ROLE OF AUTOLOGOUS CHONDROCYTE IMPLANTATION (ACI) IN THE TR
• Slide 4
• AUTOLOGOUS CHONDROCYTE GRAFTS MULTICENTRIC TRIAL WITH 28 KNEE
• Slide 6
• Slide 7
• Articular Cartilage
• Hyaline Cartilage Structure 1048715The ldquostuffrdquo of cartilage
• Slide 11
• Cartilage Injury Occurs in Many Forms
• Articular Cartilage Defects a treatment challenge
• AND WHAT IS IN OUR BASKET
• SO IT LED US TO SEARCH OF MORE PROMISING OPTION
• Autologous Chondrocyte Implantation (ACI) BACKGROUND
• Identifying a Carticelreg Patient
• Identifying a Carticelreg Patienthelliphellip
• Pre-requisite for surgery
• Autologous Chondrocyte Implantation (ACI)
• Techniques
• ACIMACI Generic Method
• Slide 23
• Treatment with CARTICEL
• CARTICEL Manufacturing and Delivery
• Step 2 Implantation
• CARTICEL Implantation
• Periosteal Patch
• Slide 29
• Slide 30
• Aci steps summarised
• Slide 32
• Complications
• Slide 34
• Slide 35
• FOLLOW UP Biopsy
• FOLLOW UP MRI
• FOLLOW UP ARTHROSCOPIC
• Rehabilitation guidelines
• ACI Rehabilitation
• ACI Rehabilitation (2)
• COMPARISON WITH OTHER METHODS OF TREATMENTS
• COMPARISON WITH OTHER METHODS OF TREATMENTShelliphelliphellip
• COMPARISON WITH OTHER METHODS OF TREATMENTShelliphelliphellip (2)
• CONCLUSIONS
• Slide 46
• Recent advancesHYAFF 3D matrix
• HYAFF-based Scaffold
• CHONDRONtrade
• RECOVERY TO
• Slide 51

Pre-requisite for surgery

Not recommended for patients who have

Appropriate biomachenical alignment

Ligamentous stabilty

Range of motion

an unstable knee

patients sensitive to materials of bovine origins

allergic to the antibiotic gentamicin

in children

yet in any joint other than the knee

AUTOLOGOUS CHONDROCYTEIMPLANTATION (ACI)

StrengthsCan produce hyaline-like cartilageCan fill defects regardless of size with functional repair tissueModerate to large defects that have failed previous interventionRepair tissue which matures rather than deteriorates over timeExpected outcomeReturn to previous level of functioning

ldquoBiological Joint replacementrdquo

LimitationsMore invasiveExpenseLonger recovery

A ACI ndash Periosteum (cells under periosteum)

B ACI ndash Chondrogide (cells under membrane)

C MACI ndash Matrix Induced ACI (cells on membrane)

Chondrogide Membrane Porcine type IIII Inert Seal Resorbs in 3-4 months

ACI MACI

TECHNIQUES

Under inert collagen membrane (ACI)

On inert collagen membrane (MACI)

Harvest 200-300mg full thickness cartilage from trochlea (non load bearing)

Cells grown on monolayer with patients serum

No cells x 20-30

ACIMACI GENERIC METHOD

ACI METHOD

TREATMENT WITH CARTICEL

Uses your own cartilage cells (chondrocytes) to repair the articular cartilage damage in your knee When implanted into a cartilage injury your own cells can form new cartilage this new cartilage is very similar to your original cartilage The CARTICEL implantation procedure is called Autologous Chondrocyte Implantation or ACI It is a two-step process

Knee Cartilage Arthroscopy and BiopsyDuring an arthroscopic procedure surgeon assesses the extent of cartilage damage amp pt as a candidate for CARTICEL implantation

ldquoBiopsyrdquo of healthy tissue about the size of a pencil eraser ie about 200 -300 mg

From outer edge of sup Med or lat Femoral condyle or inner edge of lat Femoral condyle at the intercondylar notch

This sample is sent to product labs

Step 1 Biopsy

Biopsy can be stored for up to two years so you can schedule your surgery at your convenience

When you are ready your cells are cultured over three to five weeks they increase to approx 12 million cells in a vial containing 03 ndash 04 cc of medium Every step of the manufacturing process is monitored to ensure high quality and safety

CARTICEL MANUFACTURING AND DELIVERY

STEP 2 IMPLANTATION

Cartilage Injury CleanedDuring this second stage arthrotomy done to expose knee and any dead or damaged tissue from the injury removed with curette leaving only healthy tissue

Biomachenical allignment procedures if required should be done in conjunction with implantation

CARTICEL IMPLANTATION

PERIOSTEAL PATCH

surgeon takes a small piece of tissue from your shin bone and sews it securely over the injury

CARTICEL Implantation surgeon injects CARTICEL under the patch

When CARTICEL is surgically implanted into a cartilage injury it can grow and form new hyaline-like cartilage with properties similar to those of the original cartilage

Repairing the injury helps to reduce pain and improve movement and function

ACI STEPS summarised

MACI METHOD

Cultured chondrocytes seeded in bilayered typeIIII collagen membrane

Implanted using fibrin glue

Matrix remodelled in months replaced by extracellular matrix regenerate

The overall failure rate is at present quoted as being 10 The two most common complications include bullloosening of the transplant tissue bullformation of fibrous tissue at the repair site and adhesions with return of pain and locking Neither of these complications usually leaves the patient in a worse condition than hisher pre-transplantation state

Other adverse events include bullpost-op haematoma (big blood clot)bullhypertrophic synovitis (angry knee) and superficial wound infection

COMPLICATIONS

IMPROVEMENTS IN CLINICAL OUTCOME

ASSESMENT OF TECHNIQUE

FOLLOW UP RESULTS

ONE YEAR ASSESSMENT

Radiographs Alignment Bone quality

MRI Healing

cartilage Graft failure

Arthroscopy + probe Graft integrity Pressure biopsy

FOLLOW UP BIOPSY

FOLLOW UP MRI

Final appearance of theperiosteum sutured overfemoral condyle defect Thecartilage cells have beeninjected under the flap and thefinal suture placed to close thecover and provide a watertightseal

FOLLOW UP ARTHROSCOPIC

Arthroscopic appearance of thesame area 12 months afterCarticeltrade implantation Thedefect is no longer visible andthere is now hyaline cartilage(biopsy proven) filling theoriginal defect site

REHABILITATION GUIDELINES

Immobilization first 12-24 hours

(CPM) after 12-24 hours for about 4 weeks

Complete joint loading from about 5th week trochleapatellafrom about 8th week condyle Back to sports Low impact rarr within 6 monthsRepeated impact rarr from 8th monthHigh impact rarr from 10-12th month

ACI REHABILITATION

Weight bearingIt is recommended to keep you in non-weight bearing until the second week after surgery (ACI) You can increase the weight bearing gradually and you may be able to sustain your full weight bearing after 6 to 12 weeks from surgery

Range of motionRecovery on your ROM (Range of Motion) is gradually increased with a continuous passive motion (CPM) machine and may be completed to 140 degrees of ROM at 6 weeks to 12 weeks after surgery

ACI REHABILITATIONIndoor exerciseYou can strenghthen your muscles surrounding the knee joint with a four point exercise as well as isometric hamstring and squatting exercises from 4 weeks to 6 weeks after surgeryYou may start performing stationary bike activity without resistance and increase the resistance gradually

Outdoor exerciseAt 13 weeks after surgery you can start walking lightly and at 10 months after surgery you can perform jogging and then you may enjoy intensity exercise like playing tennis or volleyball from 18 months after surgery

Rehabilitation Goals at 12 weeks after ACIFull ROM (Range of Motion) Minimal edema level Minimal occasional pain Pain free tolerance to transitional phase exercise with adequate stability and motor control

COMPARISON WITH OTHER METHODS OF TREATMENTS

Autologous Chondrocyte Implantation Aims to increase the best condition for cartilage defectAdvantagesbullHyaline cartilage is formed bullPermanent reconstructed cartilage tissue bullMost valuable treatment

bullWith Fourth Generation ACI Use of cell ndash gel mixture (collagen hyaluronic acid and fibrin) has fast gelling properties (1 ndash 5 min) upon transplantation bullNo membrane or periosteal patch bullMinimal surgical exposure and reduced surgery time bullCorrects evenly irregular defect shapes bullApplicable to larger defects

COMPARISON WITH OTHER METHODS OF TREATMENTShelliphelliphellip

Abrasion arthroplastyAims to decrease the inflammation of the jointDisadvantagesbullRemoves many cartilage fragments from the jointbullSymptoms reoccur within one year

Drilling and MicrofractureAims to generate a healing responseDisadvantagesbullThe healing response in inadequate bullNo hyaline cartilage is formed but rather fibrocartilage bullHas a limited lifespan of approximately one year bullRapid deterioration after such procedures can be expected

COMPARISON WITH OTHER METHODS OF TREATMENTShelliphelliphellip

Perichondral ResurfacingDisadvantagesbullIsolated cartilage defects are often too large to be covered byh perichondrum bullLong term follow-up of such procedures indicate that the implants undergo endochondral ossification

Synthetic Materials (ie Carbon Fiber Mesh)Disadvantagesbull It often results in fibrous tissue formation bullNot adequate biomechanically bullOften the cause for synovitis in the joints

Osteocartiloginous GraftsAims to reconstruct jointsDisadvantagesbullUnless fresh cartilage is transplanted the cartilage is dead bullFresh grafts are not commonly used as they inevitably carry a risk of disease transmission bullCyropreserved grafts can survive for many years but ultimately deteriorate

Results of the Carticeltrade procedure have been encouraging although it is not always successful An analysis was done of the US and Swedish registry of 153 consecutive patients undergoing this procedure with follow-up from 1 week to 94 months The following results were obtainedbull Patients with clinical improvement 85bull Good or Excellent results 42 bull Good or Excellent results at 2 yearspersisting at 5 years post-op 97

Thus a total of 85 of patients showed some or complete improvement with theimplantation technique The Carticel procedure demonstrated good durability at 5-10 years out

CONCLUSIONS

CONCLUSIONS ACI Vs MACI No current evidence to justify aggressive treatment of

asymptomatic lesions with ACIMACI

Patients with full thickness symptomatic defects do poorly if left untreated

ACI and MACI lead to significant improvement in objective and patient reported clinical outcome scores for up to ten years(even among those with previous failed marrow stimulation techniques)

MACI has a superior rate of clinical improvement in comparison to ACI

Repair tissue may remodel and improve in quality with time

ACI and MACI comparable at 6 years

RECENT ADVANCESHYAFF 3D MATRIX

HYAFF biomaterialscontain high quantities ofderivatized HA

HA-richchondrocyte compatibleembryonic-like mileuconductive to regenerativehealing patterns

bull Non woven felt 2 mm thick fiber diameter 10 micronsbull Chondrocytes are isolated and passaged in culture on plasticdishes up to 3 weeksbull Cells are seeded for 2 weeks on HYAFF scaffold at a density of1 x 106 cm2 resulting in a total of 4 x 106 cm2 seeded cells pergraft

HYAFF-BASED SCAFFOLD

CHONDRONtrade

Uses a cell ndash gel mixture (includes collagen hyaluronic acid and fibrin) that has fast gelling properties (1 ndash 5 min) upon transplantation

This cell and gel mixture enable even cell distribution three-dimensionally moldable to fit irregular defect shape and applicable to a larger defectThus there is minimal surgical exposure and reduced surgery time

(three-dimensional reconstruction of a chondron from the growth plate of the murine long bone the model was generated from multiple sections imaged in an electron microscope plasma membranes are coloured green and internal organelles are visible within the top cell)

RECOVERY TO

HEALTHY ACTIVE LIFE

THANK YOU

• journal club (22-10-09)
• topic autologus chondrocyte implantation
• THE ROLE OF AUTOLOGOUS CHONDROCYTE IMPLANTATION (ACI) IN THE TR
• Slide 4
• AUTOLOGOUS CHONDROCYTE GRAFTS MULTICENTRIC TRIAL WITH 28 KNEE
• Slide 6
• Slide 7
• Articular Cartilage
• Hyaline Cartilage Structure 1048715The ldquostuffrdquo of cartilage
• Slide 11
• Cartilage Injury Occurs in Many Forms
• Articular Cartilage Defects a treatment challenge
• AND WHAT IS IN OUR BASKET
• SO IT LED US TO SEARCH OF MORE PROMISING OPTION
• Autologous Chondrocyte Implantation (ACI) BACKGROUND
• Identifying a Carticelreg Patient
• Identifying a Carticelreg Patienthelliphellip
• Pre-requisite for surgery
• Autologous Chondrocyte Implantation (ACI)
• Techniques
• ACIMACI Generic Method
• Slide 23
• Treatment with CARTICEL
• CARTICEL Manufacturing and Delivery
• Step 2 Implantation
• CARTICEL Implantation
• Periosteal Patch
• Slide 29
• Slide 30
• Aci steps summarised
• Slide 32
• Complications
• Slide 34
• Slide 35
• FOLLOW UP Biopsy
• FOLLOW UP MRI
• FOLLOW UP ARTHROSCOPIC
• Rehabilitation guidelines
• ACI Rehabilitation
• ACI Rehabilitation (2)
• COMPARISON WITH OTHER METHODS OF TREATMENTS
• COMPARISON WITH OTHER METHODS OF TREATMENTShelliphelliphellip
• COMPARISON WITH OTHER METHODS OF TREATMENTShelliphelliphellip (2)
• CONCLUSIONS
• Slide 46
• Recent advancesHYAFF 3D matrix
• HYAFF-based Scaffold
• CHONDRONtrade
• RECOVERY TO
• Slide 51

AUTOLOGOUS CHONDROCYTEIMPLANTATION (ACI)

StrengthsCan produce hyaline-like cartilageCan fill defects regardless of size with functional repair tissueModerate to large defects that have failed previous interventionRepair tissue which matures rather than deteriorates over timeExpected outcomeReturn to previous level of functioning

ldquoBiological Joint replacementrdquo

LimitationsMore invasiveExpenseLonger recovery

A ACI ndash Periosteum (cells under periosteum)

B ACI ndash Chondrogide (cells under membrane)

C MACI ndash Matrix Induced ACI (cells on membrane)

Chondrogide Membrane Porcine type IIII Inert Seal Resorbs in 3-4 months

ACI MACI

TECHNIQUES

Under inert collagen membrane (ACI)

On inert collagen membrane (MACI)

Harvest 200-300mg full thickness cartilage from trochlea (non load bearing)

Cells grown on monolayer with patients serum

No cells x 20-30

ACIMACI GENERIC METHOD

ACI METHOD

TREATMENT WITH CARTICEL

Uses your own cartilage cells (chondrocytes) to repair the articular cartilage damage in your knee When implanted into a cartilage injury your own cells can form new cartilage this new cartilage is very similar to your original cartilage The CARTICEL implantation procedure is called Autologous Chondrocyte Implantation or ACI It is a two-step process

Knee Cartilage Arthroscopy and BiopsyDuring an arthroscopic procedure surgeon assesses the extent of cartilage damage amp pt as a candidate for CARTICEL implantation

ldquoBiopsyrdquo of healthy tissue about the size of a pencil eraser ie about 200 -300 mg

From outer edge of sup Med or lat Femoral condyle or inner edge of lat Femoral condyle at the intercondylar notch

This sample is sent to product labs

Step 1 Biopsy

Biopsy can be stored for up to two years so you can schedule your surgery at your convenience

When you are ready your cells are cultured over three to five weeks they increase to approx 12 million cells in a vial containing 03 ndash 04 cc of medium Every step of the manufacturing process is monitored to ensure high quality and safety

CARTICEL MANUFACTURING AND DELIVERY

STEP 2 IMPLANTATION

Cartilage Injury CleanedDuring this second stage arthrotomy done to expose knee and any dead or damaged tissue from the injury removed with curette leaving only healthy tissue

Biomachenical allignment procedures if required should be done in conjunction with implantation

CARTICEL IMPLANTATION

PERIOSTEAL PATCH

surgeon takes a small piece of tissue from your shin bone and sews it securely over the injury

CARTICEL Implantation surgeon injects CARTICEL under the patch

When CARTICEL is surgically implanted into a cartilage injury it can grow and form new hyaline-like cartilage with properties similar to those of the original cartilage

Repairing the injury helps to reduce pain and improve movement and function

ACI STEPS summarised

MACI METHOD

Cultured chondrocytes seeded in bilayered typeIIII collagen membrane

Implanted using fibrin glue

Matrix remodelled in months replaced by extracellular matrix regenerate

The overall failure rate is at present quoted as being 10 The two most common complications include bullloosening of the transplant tissue bullformation of fibrous tissue at the repair site and adhesions with return of pain and locking Neither of these complications usually leaves the patient in a worse condition than hisher pre-transplantation state

Other adverse events include bullpost-op haematoma (big blood clot)bullhypertrophic synovitis (angry knee) and superficial wound infection

COMPLICATIONS

IMPROVEMENTS IN CLINICAL OUTCOME

ASSESMENT OF TECHNIQUE

FOLLOW UP RESULTS

ONE YEAR ASSESSMENT

Radiographs Alignment Bone quality

MRI Healing

cartilage Graft failure

Arthroscopy + probe Graft integrity Pressure biopsy

FOLLOW UP BIOPSY

FOLLOW UP MRI

Final appearance of theperiosteum sutured overfemoral condyle defect Thecartilage cells have beeninjected under the flap and thefinal suture placed to close thecover and provide a watertightseal

FOLLOW UP ARTHROSCOPIC

Arthroscopic appearance of thesame area 12 months afterCarticeltrade implantation Thedefect is no longer visible andthere is now hyaline cartilage(biopsy proven) filling theoriginal defect site

REHABILITATION GUIDELINES

Immobilization first 12-24 hours

(CPM) after 12-24 hours for about 4 weeks

Complete joint loading from about 5th week trochleapatellafrom about 8th week condyle Back to sports Low impact rarr within 6 monthsRepeated impact rarr from 8th monthHigh impact rarr from 10-12th month

ACI REHABILITATION

Weight bearingIt is recommended to keep you in non-weight bearing until the second week after surgery (ACI) You can increase the weight bearing gradually and you may be able to sustain your full weight bearing after 6 to 12 weeks from surgery

Range of motionRecovery on your ROM (Range of Motion) is gradually increased with a continuous passive motion (CPM) machine and may be completed to 140 degrees of ROM at 6 weeks to 12 weeks after surgery

ACI REHABILITATIONIndoor exerciseYou can strenghthen your muscles surrounding the knee joint with a four point exercise as well as isometric hamstring and squatting exercises from 4 weeks to 6 weeks after surgeryYou may start performing stationary bike activity without resistance and increase the resistance gradually

Outdoor exerciseAt 13 weeks after surgery you can start walking lightly and at 10 months after surgery you can perform jogging and then you may enjoy intensity exercise like playing tennis or volleyball from 18 months after surgery

Rehabilitation Goals at 12 weeks after ACIFull ROM (Range of Motion) Minimal edema level Minimal occasional pain Pain free tolerance to transitional phase exercise with adequate stability and motor control

COMPARISON WITH OTHER METHODS OF TREATMENTS

Autologous Chondrocyte Implantation Aims to increase the best condition for cartilage defectAdvantagesbullHyaline cartilage is formed bullPermanent reconstructed cartilage tissue bullMost valuable treatment

bullWith Fourth Generation ACI Use of cell ndash gel mixture (collagen hyaluronic acid and fibrin) has fast gelling properties (1 ndash 5 min) upon transplantation bullNo membrane or periosteal patch bullMinimal surgical exposure and reduced surgery time bullCorrects evenly irregular defect shapes bullApplicable to larger defects

COMPARISON WITH OTHER METHODS OF TREATMENTShelliphelliphellip

Abrasion arthroplastyAims to decrease the inflammation of the jointDisadvantagesbullRemoves many cartilage fragments from the jointbullSymptoms reoccur within one year

Drilling and MicrofractureAims to generate a healing responseDisadvantagesbullThe healing response in inadequate bullNo hyaline cartilage is formed but rather fibrocartilage bullHas a limited lifespan of approximately one year bullRapid deterioration after such procedures can be expected

COMPARISON WITH OTHER METHODS OF TREATMENTShelliphelliphellip

Perichondral ResurfacingDisadvantagesbullIsolated cartilage defects are often too large to be covered byh perichondrum bullLong term follow-up of such procedures indicate that the implants undergo endochondral ossification

Synthetic Materials (ie Carbon Fiber Mesh)Disadvantagesbull It often results in fibrous tissue formation bullNot adequate biomechanically bullOften the cause for synovitis in the joints

Osteocartiloginous GraftsAims to reconstruct jointsDisadvantagesbullUnless fresh cartilage is transplanted the cartilage is dead bullFresh grafts are not commonly used as they inevitably carry a risk of disease transmission bullCyropreserved grafts can survive for many years but ultimately deteriorate

Results of the Carticeltrade procedure have been encouraging although it is not always successful An analysis was done of the US and Swedish registry of 153 consecutive patients undergoing this procedure with follow-up from 1 week to 94 months The following results were obtainedbull Patients with clinical improvement 85bull Good or Excellent results 42 bull Good or Excellent results at 2 yearspersisting at 5 years post-op 97

Thus a total of 85 of patients showed some or complete improvement with theimplantation technique The Carticel procedure demonstrated good durability at 5-10 years out

CONCLUSIONS

CONCLUSIONS ACI Vs MACI No current evidence to justify aggressive treatment of

asymptomatic lesions with ACIMACI

Patients with full thickness symptomatic defects do poorly if left untreated

ACI and MACI lead to significant improvement in objective and patient reported clinical outcome scores for up to ten years(even among those with previous failed marrow stimulation techniques)

MACI has a superior rate of clinical improvement in comparison to ACI

Repair tissue may remodel and improve in quality with time

ACI and MACI comparable at 6 years

RECENT ADVANCESHYAFF 3D MATRIX

HYAFF biomaterialscontain high quantities ofderivatized HA

HA-richchondrocyte compatibleembryonic-like mileuconductive to regenerativehealing patterns

bull Non woven felt 2 mm thick fiber diameter 10 micronsbull Chondrocytes are isolated and passaged in culture on plasticdishes up to 3 weeksbull Cells are seeded for 2 weeks on HYAFF scaffold at a density of1 x 106 cm2 resulting in a total of 4 x 106 cm2 seeded cells pergraft

HYAFF-BASED SCAFFOLD

CHONDRONtrade

Uses a cell ndash gel mixture (includes collagen hyaluronic acid and fibrin) that has fast gelling properties (1 ndash 5 min) upon transplantation

This cell and gel mixture enable even cell distribution three-dimensionally moldable to fit irregular defect shape and applicable to a larger defectThus there is minimal surgical exposure and reduced surgery time

(three-dimensional reconstruction of a chondron from the growth plate of the murine long bone the model was generated from multiple sections imaged in an electron microscope plasma membranes are coloured green and internal organelles are visible within the top cell)

RECOVERY TO

HEALTHY ACTIVE LIFE

THANK YOU

• journal club (22-10-09)
• topic autologus chondrocyte implantation
• THE ROLE OF AUTOLOGOUS CHONDROCYTE IMPLANTATION (ACI) IN THE TR
• Slide 4
• AUTOLOGOUS CHONDROCYTE GRAFTS MULTICENTRIC TRIAL WITH 28 KNEE
• Slide 6
• Slide 7
• Articular Cartilage
• Hyaline Cartilage Structure 1048715The ldquostuffrdquo of cartilage
• Slide 11
• Cartilage Injury Occurs in Many Forms
• Articular Cartilage Defects a treatment challenge
• AND WHAT IS IN OUR BASKET
• SO IT LED US TO SEARCH OF MORE PROMISING OPTION
• Autologous Chondrocyte Implantation (ACI) BACKGROUND
• Identifying a Carticelreg Patient
• Identifying a Carticelreg Patienthelliphellip
• Pre-requisite for surgery
• Autologous Chondrocyte Implantation (ACI)
• Techniques
• ACIMACI Generic Method
• Slide 23
• Treatment with CARTICEL
• CARTICEL Manufacturing and Delivery
• Step 2 Implantation
• CARTICEL Implantation
• Periosteal Patch
• Slide 29
• Slide 30
• Aci steps summarised
• Slide 32
• Complications
• Slide 34
• Slide 35
• FOLLOW UP Biopsy
• FOLLOW UP MRI
• FOLLOW UP ARTHROSCOPIC
• Rehabilitation guidelines
• ACI Rehabilitation
• ACI Rehabilitation (2)
• COMPARISON WITH OTHER METHODS OF TREATMENTS
• COMPARISON WITH OTHER METHODS OF TREATMENTShelliphelliphellip
• COMPARISON WITH OTHER METHODS OF TREATMENTShelliphelliphellip (2)
• CONCLUSIONS
• Slide 46
• Recent advancesHYAFF 3D matrix
• HYAFF-based Scaffold
• CHONDRONtrade
• RECOVERY TO
• Slide 51

A ACI ndash Periosteum (cells under periosteum)

B ACI ndash Chondrogide (cells under membrane)

C MACI ndash Matrix Induced ACI (cells on membrane)

Chondrogide Membrane Porcine type IIII Inert Seal Resorbs in 3-4 months

ACI MACI

TECHNIQUES

Under inert collagen membrane (ACI)

On inert collagen membrane (MACI)

Harvest 200-300mg full thickness cartilage from trochlea (non load bearing)

Cells grown on monolayer with patients serum

No cells x 20-30

ACIMACI GENERIC METHOD

ACI METHOD

TREATMENT WITH CARTICEL

Uses your own cartilage cells (chondrocytes) to repair the articular cartilage damage in your knee When implanted into a cartilage injury your own cells can form new cartilage this new cartilage is very similar to your original cartilage The CARTICEL implantation procedure is called Autologous Chondrocyte Implantation or ACI It is a two-step process

Knee Cartilage Arthroscopy and BiopsyDuring an arthroscopic procedure surgeon assesses the extent of cartilage damage amp pt as a candidate for CARTICEL implantation

ldquoBiopsyrdquo of healthy tissue about the size of a pencil eraser ie about 200 -300 mg

From outer edge of sup Med or lat Femoral condyle or inner edge of lat Femoral condyle at the intercondylar notch

This sample is sent to product labs

Step 1 Biopsy

Biopsy can be stored for up to two years so you can schedule your surgery at your convenience

When you are ready your cells are cultured over three to five weeks they increase to approx 12 million cells in a vial containing 03 ndash 04 cc of medium Every step of the manufacturing process is monitored to ensure high quality and safety

CARTICEL MANUFACTURING AND DELIVERY

STEP 2 IMPLANTATION

Cartilage Injury CleanedDuring this second stage arthrotomy done to expose knee and any dead or damaged tissue from the injury removed with curette leaving only healthy tissue

Biomachenical allignment procedures if required should be done in conjunction with implantation

CARTICEL IMPLANTATION

PERIOSTEAL PATCH

surgeon takes a small piece of tissue from your shin bone and sews it securely over the injury

CARTICEL Implantation surgeon injects CARTICEL under the patch

When CARTICEL is surgically implanted into a cartilage injury it can grow and form new hyaline-like cartilage with properties similar to those of the original cartilage

Repairing the injury helps to reduce pain and improve movement and function

ACI STEPS summarised

MACI METHOD

Cultured chondrocytes seeded in bilayered typeIIII collagen membrane

Implanted using fibrin glue

Matrix remodelled in months replaced by extracellular matrix regenerate

The overall failure rate is at present quoted as being 10 The two most common complications include bullloosening of the transplant tissue bullformation of fibrous tissue at the repair site and adhesions with return of pain and locking Neither of these complications usually leaves the patient in a worse condition than hisher pre-transplantation state

Other adverse events include bullpost-op haematoma (big blood clot)bullhypertrophic synovitis (angry knee) and superficial wound infection

COMPLICATIONS

IMPROVEMENTS IN CLINICAL OUTCOME

ASSESMENT OF TECHNIQUE

FOLLOW UP RESULTS

ONE YEAR ASSESSMENT

Radiographs Alignment Bone quality

MRI Healing

cartilage Graft failure

Arthroscopy + probe Graft integrity Pressure biopsy

FOLLOW UP BIOPSY

FOLLOW UP MRI

Final appearance of theperiosteum sutured overfemoral condyle defect Thecartilage cells have beeninjected under the flap and thefinal suture placed to close thecover and provide a watertightseal

FOLLOW UP ARTHROSCOPIC

Arthroscopic appearance of thesame area 12 months afterCarticeltrade implantation Thedefect is no longer visible andthere is now hyaline cartilage(biopsy proven) filling theoriginal defect site

REHABILITATION GUIDELINES

Immobilization first 12-24 hours

(CPM) after 12-24 hours for about 4 weeks

Complete joint loading from about 5th week trochleapatellafrom about 8th week condyle Back to sports Low impact rarr within 6 monthsRepeated impact rarr from 8th monthHigh impact rarr from 10-12th month

ACI REHABILITATION

Weight bearingIt is recommended to keep you in non-weight bearing until the second week after surgery (ACI) You can increase the weight bearing gradually and you may be able to sustain your full weight bearing after 6 to 12 weeks from surgery

Range of motionRecovery on your ROM (Range of Motion) is gradually increased with a continuous passive motion (CPM) machine and may be completed to 140 degrees of ROM at 6 weeks to 12 weeks after surgery

ACI REHABILITATIONIndoor exerciseYou can strenghthen your muscles surrounding the knee joint with a four point exercise as well as isometric hamstring and squatting exercises from 4 weeks to 6 weeks after surgeryYou may start performing stationary bike activity without resistance and increase the resistance gradually

Outdoor exerciseAt 13 weeks after surgery you can start walking lightly and at 10 months after surgery you can perform jogging and then you may enjoy intensity exercise like playing tennis or volleyball from 18 months after surgery

Rehabilitation Goals at 12 weeks after ACIFull ROM (Range of Motion) Minimal edema level Minimal occasional pain Pain free tolerance to transitional phase exercise with adequate stability and motor control

COMPARISON WITH OTHER METHODS OF TREATMENTS

Autologous Chondrocyte Implantation Aims to increase the best condition for cartilage defectAdvantagesbullHyaline cartilage is formed bullPermanent reconstructed cartilage tissue bullMost valuable treatment

bullWith Fourth Generation ACI Use of cell ndash gel mixture (collagen hyaluronic acid and fibrin) has fast gelling properties (1 ndash 5 min) upon transplantation bullNo membrane or periosteal patch bullMinimal surgical exposure and reduced surgery time bullCorrects evenly irregular defect shapes bullApplicable to larger defects

COMPARISON WITH OTHER METHODS OF TREATMENTShelliphelliphellip

Abrasion arthroplastyAims to decrease the inflammation of the jointDisadvantagesbullRemoves many cartilage fragments from the jointbullSymptoms reoccur within one year

Drilling and MicrofractureAims to generate a healing responseDisadvantagesbullThe healing response in inadequate bullNo hyaline cartilage is formed but rather fibrocartilage bullHas a limited lifespan of approximately one year bullRapid deterioration after such procedures can be expected

COMPARISON WITH OTHER METHODS OF TREATMENTShelliphelliphellip

Perichondral ResurfacingDisadvantagesbullIsolated cartilage defects are often too large to be covered byh perichondrum bullLong term follow-up of such procedures indicate that the implants undergo endochondral ossification

Synthetic Materials (ie Carbon Fiber Mesh)Disadvantagesbull It often results in fibrous tissue formation bullNot adequate biomechanically bullOften the cause for synovitis in the joints

Osteocartiloginous GraftsAims to reconstruct jointsDisadvantagesbullUnless fresh cartilage is transplanted the cartilage is dead bullFresh grafts are not commonly used as they inevitably carry a risk of disease transmission bullCyropreserved grafts can survive for many years but ultimately deteriorate

Results of the Carticeltrade procedure have been encouraging although it is not always successful An analysis was done of the US and Swedish registry of 153 consecutive patients undergoing this procedure with follow-up from 1 week to 94 months The following results were obtainedbull Patients with clinical improvement 85bull Good or Excellent results 42 bull Good or Excellent results at 2 yearspersisting at 5 years post-op 97

Thus a total of 85 of patients showed some or complete improvement with theimplantation technique The Carticel procedure demonstrated good durability at 5-10 years out

CONCLUSIONS

CONCLUSIONS ACI Vs MACI No current evidence to justify aggressive treatment of

asymptomatic lesions with ACIMACI

Patients with full thickness symptomatic defects do poorly if left untreated

ACI and MACI lead to significant improvement in objective and patient reported clinical outcome scores for up to ten years(even among those with previous failed marrow stimulation techniques)

MACI has a superior rate of clinical improvement in comparison to ACI

Repair tissue may remodel and improve in quality with time

ACI and MACI comparable at 6 years

RECENT ADVANCESHYAFF 3D MATRIX

HYAFF biomaterialscontain high quantities ofderivatized HA

HA-richchondrocyte compatibleembryonic-like mileuconductive to regenerativehealing patterns

bull Non woven felt 2 mm thick fiber diameter 10 micronsbull Chondrocytes are isolated and passaged in culture on plasticdishes up to 3 weeksbull Cells are seeded for 2 weeks on HYAFF scaffold at a density of1 x 106 cm2 resulting in a total of 4 x 106 cm2 seeded cells pergraft

HYAFF-BASED SCAFFOLD

CHONDRONtrade

Uses a cell ndash gel mixture (includes collagen hyaluronic acid and fibrin) that has fast gelling properties (1 ndash 5 min) upon transplantation

This cell and gel mixture enable even cell distribution three-dimensionally moldable to fit irregular defect shape and applicable to a larger defectThus there is minimal surgical exposure and reduced surgery time

(three-dimensional reconstruction of a chondron from the growth plate of the murine long bone the model was generated from multiple sections imaged in an electron microscope plasma membranes are coloured green and internal organelles are visible within the top cell)

RECOVERY TO

HEALTHY ACTIVE LIFE

THANK YOU

• journal club (22-10-09)
• topic autologus chondrocyte implantation
• THE ROLE OF AUTOLOGOUS CHONDROCYTE IMPLANTATION (ACI) IN THE TR
• Slide 4
• AUTOLOGOUS CHONDROCYTE GRAFTS MULTICENTRIC TRIAL WITH 28 KNEE
• Slide 6
• Slide 7
• Articular Cartilage
• Hyaline Cartilage Structure 1048715The ldquostuffrdquo of cartilage
• Slide 11
• Cartilage Injury Occurs in Many Forms
• Articular Cartilage Defects a treatment challenge
• AND WHAT IS IN OUR BASKET
• SO IT LED US TO SEARCH OF MORE PROMISING OPTION
• Autologous Chondrocyte Implantation (ACI) BACKGROUND
• Identifying a Carticelreg Patient
• Identifying a Carticelreg Patienthelliphellip
• Pre-requisite for surgery
• Autologous Chondrocyte Implantation (ACI)
• Techniques
• ACIMACI Generic Method
• Slide 23
• Treatment with CARTICEL
• CARTICEL Manufacturing and Delivery
• Step 2 Implantation
• CARTICEL Implantation
• Periosteal Patch
• Slide 29
• Slide 30
• Aci steps summarised
• Slide 32
• Complications
• Slide 34
• Slide 35
• FOLLOW UP Biopsy
• FOLLOW UP MRI
• FOLLOW UP ARTHROSCOPIC
• Rehabilitation guidelines
• ACI Rehabilitation
• ACI Rehabilitation (2)
• COMPARISON WITH OTHER METHODS OF TREATMENTS
• COMPARISON WITH OTHER METHODS OF TREATMENTShelliphelliphellip
• COMPARISON WITH OTHER METHODS OF TREATMENTShelliphelliphellip (2)
• CONCLUSIONS
• Slide 46
• Recent advancesHYAFF 3D matrix
• HYAFF-based Scaffold
• CHONDRONtrade
• RECOVERY TO
• Slide 51

Under inert collagen membrane (ACI)

On inert collagen membrane (MACI)

Harvest 200-300mg full thickness cartilage from trochlea (non load bearing)

Cells grown on monolayer with patients serum

No cells x 20-30

ACIMACI GENERIC METHOD

ACI METHOD

TREATMENT WITH CARTICEL

Uses your own cartilage cells (chondrocytes) to repair the articular cartilage damage in your knee When implanted into a cartilage injury your own cells can form new cartilage this new cartilage is very similar to your original cartilage The CARTICEL implantation procedure is called Autologous Chondrocyte Implantation or ACI It is a two-step process

Knee Cartilage Arthroscopy and BiopsyDuring an arthroscopic procedure surgeon assesses the extent of cartilage damage amp pt as a candidate for CARTICEL implantation

ldquoBiopsyrdquo of healthy tissue about the size of a pencil eraser ie about 200 -300 mg

From outer edge of sup Med or lat Femoral condyle or inner edge of lat Femoral condyle at the intercondylar notch

This sample is sent to product labs

Step 1 Biopsy

Biopsy can be stored for up to two years so you can schedule your surgery at your convenience

When you are ready your cells are cultured over three to five weeks they increase to approx 12 million cells in a vial containing 03 ndash 04 cc of medium Every step of the manufacturing process is monitored to ensure high quality and safety

CARTICEL MANUFACTURING AND DELIVERY

STEP 2 IMPLANTATION

Cartilage Injury CleanedDuring this second stage arthrotomy done to expose knee and any dead or damaged tissue from the injury removed with curette leaving only healthy tissue

Biomachenical allignment procedures if required should be done in conjunction with implantation

CARTICEL IMPLANTATION

PERIOSTEAL PATCH

surgeon takes a small piece of tissue from your shin bone and sews it securely over the injury

CARTICEL Implantation surgeon injects CARTICEL under the patch

When CARTICEL is surgically implanted into a cartilage injury it can grow and form new hyaline-like cartilage with properties similar to those of the original cartilage

Repairing the injury helps to reduce pain and improve movement and function

ACI STEPS summarised

MACI METHOD

Cultured chondrocytes seeded in bilayered typeIIII collagen membrane

Implanted using fibrin glue

Matrix remodelled in months replaced by extracellular matrix regenerate

The overall failure rate is at present quoted as being 10 The two most common complications include bullloosening of the transplant tissue bullformation of fibrous tissue at the repair site and adhesions with return of pain and locking Neither of these complications usually leaves the patient in a worse condition than hisher pre-transplantation state

Other adverse events include bullpost-op haematoma (big blood clot)bullhypertrophic synovitis (angry knee) and superficial wound infection

COMPLICATIONS

IMPROVEMENTS IN CLINICAL OUTCOME

ASSESMENT OF TECHNIQUE

FOLLOW UP RESULTS

ONE YEAR ASSESSMENT

Radiographs Alignment Bone quality

MRI Healing

cartilage Graft failure

Arthroscopy + probe Graft integrity Pressure biopsy

FOLLOW UP BIOPSY

FOLLOW UP MRI

Final appearance of theperiosteum sutured overfemoral condyle defect Thecartilage cells have beeninjected under the flap and thefinal suture placed to close thecover and provide a watertightseal

FOLLOW UP ARTHROSCOPIC

Arthroscopic appearance of thesame area 12 months afterCarticeltrade implantation Thedefect is no longer visible andthere is now hyaline cartilage(biopsy proven) filling theoriginal defect site

REHABILITATION GUIDELINES

Immobilization first 12-24 hours

(CPM) after 12-24 hours for about 4 weeks

Complete joint loading from about 5th week trochleapatellafrom about 8th week condyle Back to sports Low impact rarr within 6 monthsRepeated impact rarr from 8th monthHigh impact rarr from 10-12th month

ACI REHABILITATION

Weight bearingIt is recommended to keep you in non-weight bearing until the second week after surgery (ACI) You can increase the weight bearing gradually and you may be able to sustain your full weight bearing after 6 to 12 weeks from surgery

Range of motionRecovery on your ROM (Range of Motion) is gradually increased with a continuous passive motion (CPM) machine and may be completed to 140 degrees of ROM at 6 weeks to 12 weeks after surgery

ACI REHABILITATIONIndoor exerciseYou can strenghthen your muscles surrounding the knee joint with a four point exercise as well as isometric hamstring and squatting exercises from 4 weeks to 6 weeks after surgeryYou may start performing stationary bike activity without resistance and increase the resistance gradually

Outdoor exerciseAt 13 weeks after surgery you can start walking lightly and at 10 months after surgery you can perform jogging and then you may enjoy intensity exercise like playing tennis or volleyball from 18 months after surgery

Rehabilitation Goals at 12 weeks after ACIFull ROM (Range of Motion) Minimal edema level Minimal occasional pain Pain free tolerance to transitional phase exercise with adequate stability and motor control

COMPARISON WITH OTHER METHODS OF TREATMENTS

Autologous Chondrocyte Implantation Aims to increase the best condition for cartilage defectAdvantagesbullHyaline cartilage is formed bullPermanent reconstructed cartilage tissue bullMost valuable treatment

bullWith Fourth Generation ACI Use of cell ndash gel mixture (collagen hyaluronic acid and fibrin) has fast gelling properties (1 ndash 5 min) upon transplantation bullNo membrane or periosteal patch bullMinimal surgical exposure and reduced surgery time bullCorrects evenly irregular defect shapes bullApplicable to larger defects

COMPARISON WITH OTHER METHODS OF TREATMENTShelliphelliphellip

Abrasion arthroplastyAims to decrease the inflammation of the jointDisadvantagesbullRemoves many cartilage fragments from the jointbullSymptoms reoccur within one year

Drilling and MicrofractureAims to generate a healing responseDisadvantagesbullThe healing response in inadequate bullNo hyaline cartilage is formed but rather fibrocartilage bullHas a limited lifespan of approximately one year bullRapid deterioration after such procedures can be expected

COMPARISON WITH OTHER METHODS OF TREATMENTShelliphelliphellip

Perichondral ResurfacingDisadvantagesbullIsolated cartilage defects are often too large to be covered byh perichondrum bullLong term follow-up of such procedures indicate that the implants undergo endochondral ossification

Synthetic Materials (ie Carbon Fiber Mesh)Disadvantagesbull It often results in fibrous tissue formation bullNot adequate biomechanically bullOften the cause for synovitis in the joints

Osteocartiloginous GraftsAims to reconstruct jointsDisadvantagesbullUnless fresh cartilage is transplanted the cartilage is dead bullFresh grafts are not commonly used as they inevitably carry a risk of disease transmission bullCyropreserved grafts can survive for many years but ultimately deteriorate

Results of the Carticeltrade procedure have been encouraging although it is not always successful An analysis was done of the US and Swedish registry of 153 consecutive patients undergoing this procedure with follow-up from 1 week to 94 months The following results were obtainedbull Patients with clinical improvement 85bull Good or Excellent results 42 bull Good or Excellent results at 2 yearspersisting at 5 years post-op 97

Thus a total of 85 of patients showed some or complete improvement with theimplantation technique The Carticel procedure demonstrated good durability at 5-10 years out

CONCLUSIONS

CONCLUSIONS ACI Vs MACI No current evidence to justify aggressive treatment of

asymptomatic lesions with ACIMACI

Patients with full thickness symptomatic defects do poorly if left untreated

ACI and MACI lead to significant improvement in objective and patient reported clinical outcome scores for up to ten years(even among those with previous failed marrow stimulation techniques)

MACI has a superior rate of clinical improvement in comparison to ACI

Repair tissue may remodel and improve in quality with time

ACI and MACI comparable at 6 years

RECENT ADVANCESHYAFF 3D MATRIX

HYAFF biomaterialscontain high quantities ofderivatized HA

HA-richchondrocyte compatibleembryonic-like mileuconductive to regenerativehealing patterns

bull Non woven felt 2 mm thick fiber diameter 10 micronsbull Chondrocytes are isolated and passaged in culture on plasticdishes up to 3 weeksbull Cells are seeded for 2 weeks on HYAFF scaffold at a density of1 x 106 cm2 resulting in a total of 4 x 106 cm2 seeded cells pergraft

HYAFF-BASED SCAFFOLD

CHONDRONtrade

Uses a cell ndash gel mixture (includes collagen hyaluronic acid and fibrin) that has fast gelling properties (1 ndash 5 min) upon transplantation

This cell and gel mixture enable even cell distribution three-dimensionally moldable to fit irregular defect shape and applicable to a larger defectThus there is minimal surgical exposure and reduced surgery time

(three-dimensional reconstruction of a chondron from the growth plate of the murine long bone the model was generated from multiple sections imaged in an electron microscope plasma membranes are coloured green and internal organelles are visible within the top cell)

RECOVERY TO

HEALTHY ACTIVE LIFE

THANK YOU

• journal club (22-10-09)
• topic autologus chondrocyte implantation
• THE ROLE OF AUTOLOGOUS CHONDROCYTE IMPLANTATION (ACI) IN THE TR
• Slide 4
• AUTOLOGOUS CHONDROCYTE GRAFTS MULTICENTRIC TRIAL WITH 28 KNEE
• Slide 6
• Slide 7
• Articular Cartilage
• Hyaline Cartilage Structure 1048715The ldquostuffrdquo of cartilage
• Slide 11
• Cartilage Injury Occurs in Many Forms
• Articular Cartilage Defects a treatment challenge
• AND WHAT IS IN OUR BASKET
• SO IT LED US TO SEARCH OF MORE PROMISING OPTION
• Autologous Chondrocyte Implantation (ACI) BACKGROUND
• Identifying a Carticelreg Patient
• Identifying a Carticelreg Patienthelliphellip
• Pre-requisite for surgery
• Autologous Chondrocyte Implantation (ACI)
• Techniques
• ACIMACI Generic Method
• Slide 23
• Treatment with CARTICEL
• CARTICEL Manufacturing and Delivery
• Step 2 Implantation
• CARTICEL Implantation
• Periosteal Patch
• Slide 29
• Slide 30
• Aci steps summarised
• Slide 32
• Complications
• Slide 34
• Slide 35
• FOLLOW UP Biopsy
• FOLLOW UP MRI
• FOLLOW UP ARTHROSCOPIC
• Rehabilitation guidelines
• ACI Rehabilitation
• ACI Rehabilitation (2)
• COMPARISON WITH OTHER METHODS OF TREATMENTS
• COMPARISON WITH OTHER METHODS OF TREATMENTShelliphelliphellip
• COMPARISON WITH OTHER METHODS OF TREATMENTShelliphelliphellip (2)
• CONCLUSIONS
• Slide 46
• Recent advancesHYAFF 3D matrix
• HYAFF-based Scaffold
• CHONDRONtrade
• RECOVERY TO
• Slide 51

ACI METHOD

TREATMENT WITH CARTICEL

Uses your own cartilage cells (chondrocytes) to repair the articular cartilage damage in your knee When implanted into a cartilage injury your own cells can form new cartilage this new cartilage is very similar to your original cartilage The CARTICEL implantation procedure is called Autologous Chondrocyte Implantation or ACI It is a two-step process

Knee Cartilage Arthroscopy and BiopsyDuring an arthroscopic procedure surgeon assesses the extent of cartilage damage amp pt as a candidate for CARTICEL implantation

ldquoBiopsyrdquo of healthy tissue about the size of a pencil eraser ie about 200 -300 mg

From outer edge of sup Med or lat Femoral condyle or inner edge of lat Femoral condyle at the intercondylar notch

This sample is sent to product labs

Step 1 Biopsy

Biopsy can be stored for up to two years so you can schedule your surgery at your convenience

When you are ready your cells are cultured over three to five weeks they increase to approx 12 million cells in a vial containing 03 ndash 04 cc of medium Every step of the manufacturing process is monitored to ensure high quality and safety

CARTICEL MANUFACTURING AND DELIVERY

STEP 2 IMPLANTATION

Cartilage Injury CleanedDuring this second stage arthrotomy done to expose knee and any dead or damaged tissue from the injury removed with curette leaving only healthy tissue

Biomachenical allignment procedures if required should be done in conjunction with implantation

CARTICEL IMPLANTATION

PERIOSTEAL PATCH

surgeon takes a small piece of tissue from your shin bone and sews it securely over the injury

CARTICEL Implantation surgeon injects CARTICEL under the patch

When CARTICEL is surgically implanted into a cartilage injury it can grow and form new hyaline-like cartilage with properties similar to those of the original cartilage

Repairing the injury helps to reduce pain and improve movement and function

ACI STEPS summarised

MACI METHOD

Cultured chondrocytes seeded in bilayered typeIIII collagen membrane

Implanted using fibrin glue

Matrix remodelled in months replaced by extracellular matrix regenerate

The overall failure rate is at present quoted as being 10 The two most common complications include bullloosening of the transplant tissue bullformation of fibrous tissue at the repair site and adhesions with return of pain and locking Neither of these complications usually leaves the patient in a worse condition than hisher pre-transplantation state

Other adverse events include bullpost-op haematoma (big blood clot)bullhypertrophic synovitis (angry knee) and superficial wound infection

COMPLICATIONS

IMPROVEMENTS IN CLINICAL OUTCOME

ASSESMENT OF TECHNIQUE

FOLLOW UP RESULTS

ONE YEAR ASSESSMENT

Radiographs Alignment Bone quality

MRI Healing

cartilage Graft failure

Arthroscopy + probe Graft integrity Pressure biopsy

FOLLOW UP BIOPSY

FOLLOW UP MRI

Final appearance of theperiosteum sutured overfemoral condyle defect Thecartilage cells have beeninjected under the flap and thefinal suture placed to close thecover and provide a watertightseal

FOLLOW UP ARTHROSCOPIC

Arthroscopic appearance of thesame area 12 months afterCarticeltrade implantation Thedefect is no longer visible andthere is now hyaline cartilage(biopsy proven) filling theoriginal defect site

REHABILITATION GUIDELINES

Immobilization first 12-24 hours

(CPM) after 12-24 hours for about 4 weeks

Complete joint loading from about 5th week trochleapatellafrom about 8th week condyle Back to sports Low impact rarr within 6 monthsRepeated impact rarr from 8th monthHigh impact rarr from 10-12th month

ACI REHABILITATION

Weight bearingIt is recommended to keep you in non-weight bearing until the second week after surgery (ACI) You can increase the weight bearing gradually and you may be able to sustain your full weight bearing after 6 to 12 weeks from surgery

Range of motionRecovery on your ROM (Range of Motion) is gradually increased with a continuous passive motion (CPM) machine and may be completed to 140 degrees of ROM at 6 weeks to 12 weeks after surgery

ACI REHABILITATIONIndoor exerciseYou can strenghthen your muscles surrounding the knee joint with a four point exercise as well as isometric hamstring and squatting exercises from 4 weeks to 6 weeks after surgeryYou may start performing stationary bike activity without resistance and increase the resistance gradually

Outdoor exerciseAt 13 weeks after surgery you can start walking lightly and at 10 months after surgery you can perform jogging and then you may enjoy intensity exercise like playing tennis or volleyball from 18 months after surgery

Rehabilitation Goals at 12 weeks after ACIFull ROM (Range of Motion) Minimal edema level Minimal occasional pain Pain free tolerance to transitional phase exercise with adequate stability and motor control

COMPARISON WITH OTHER METHODS OF TREATMENTS

Autologous Chondrocyte Implantation Aims to increase the best condition for cartilage defectAdvantagesbullHyaline cartilage is formed bullPermanent reconstructed cartilage tissue bullMost valuable treatment

bullWith Fourth Generation ACI Use of cell ndash gel mixture (collagen hyaluronic acid and fibrin) has fast gelling properties (1 ndash 5 min) upon transplantation bullNo membrane or periosteal patch bullMinimal surgical exposure and reduced surgery time bullCorrects evenly irregular defect shapes bullApplicable to larger defects

COMPARISON WITH OTHER METHODS OF TREATMENTShelliphelliphellip

Abrasion arthroplastyAims to decrease the inflammation of the jointDisadvantagesbullRemoves many cartilage fragments from the jointbullSymptoms reoccur within one year

Drilling and MicrofractureAims to generate a healing responseDisadvantagesbullThe healing response in inadequate bullNo hyaline cartilage is formed but rather fibrocartilage bullHas a limited lifespan of approximately one year bullRapid deterioration after such procedures can be expected

COMPARISON WITH OTHER METHODS OF TREATMENTShelliphelliphellip

Perichondral ResurfacingDisadvantagesbullIsolated cartilage defects are often too large to be covered byh perichondrum bullLong term follow-up of such procedures indicate that the implants undergo endochondral ossification

Synthetic Materials (ie Carbon Fiber Mesh)Disadvantagesbull It often results in fibrous tissue formation bullNot adequate biomechanically bullOften the cause for synovitis in the joints

Osteocartiloginous GraftsAims to reconstruct jointsDisadvantagesbullUnless fresh cartilage is transplanted the cartilage is dead bullFresh grafts are not commonly used as they inevitably carry a risk of disease transmission bullCyropreserved grafts can survive for many years but ultimately deteriorate

Results of the Carticeltrade procedure have been encouraging although it is not always successful An analysis was done of the US and Swedish registry of 153 consecutive patients undergoing this procedure with follow-up from 1 week to 94 months The following results were obtainedbull Patients with clinical improvement 85bull Good or Excellent results 42 bull Good or Excellent results at 2 yearspersisting at 5 years post-op 97

Thus a total of 85 of patients showed some or complete improvement with theimplantation technique The Carticel procedure demonstrated good durability at 5-10 years out

CONCLUSIONS

CONCLUSIONS ACI Vs MACI No current evidence to justify aggressive treatment of

asymptomatic lesions with ACIMACI

Patients with full thickness symptomatic defects do poorly if left untreated

ACI and MACI lead to significant improvement in objective and patient reported clinical outcome scores for up to ten years(even among those with previous failed marrow stimulation techniques)

MACI has a superior rate of clinical improvement in comparison to ACI

Repair tissue may remodel and improve in quality with time

ACI and MACI comparable at 6 years

RECENT ADVANCESHYAFF 3D MATRIX

HYAFF biomaterialscontain high quantities ofderivatized HA

HA-richchondrocyte compatibleembryonic-like mileuconductive to regenerativehealing patterns

bull Non woven felt 2 mm thick fiber diameter 10 micronsbull Chondrocytes are isolated and passaged in culture on plasticdishes up to 3 weeksbull Cells are seeded for 2 weeks on HYAFF scaffold at a density of1 x 106 cm2 resulting in a total of 4 x 106 cm2 seeded cells pergraft

HYAFF-BASED SCAFFOLD

CHONDRONtrade

Uses a cell ndash gel mixture (includes collagen hyaluronic acid and fibrin) that has fast gelling properties (1 ndash 5 min) upon transplantation

This cell and gel mixture enable even cell distribution three-dimensionally moldable to fit irregular defect shape and applicable to a larger defectThus there is minimal surgical exposure and reduced surgery time

(three-dimensional reconstruction of a chondron from the growth plate of the murine long bone the model was generated from multiple sections imaged in an electron microscope plasma membranes are coloured green and internal organelles are visible within the top cell)

RECOVERY TO

HEALTHY ACTIVE LIFE

THANK YOU

• journal club (22-10-09)
• topic autologus chondrocyte implantation
• THE ROLE OF AUTOLOGOUS CHONDROCYTE IMPLANTATION (ACI) IN THE TR
• Slide 4
• AUTOLOGOUS CHONDROCYTE GRAFTS MULTICENTRIC TRIAL WITH 28 KNEE
• Slide 6
• Slide 7
• Articular Cartilage
• Hyaline Cartilage Structure 1048715The ldquostuffrdquo of cartilage
• Slide 11
• Cartilage Injury Occurs in Many Forms
• Articular Cartilage Defects a treatment challenge
• AND WHAT IS IN OUR BASKET
• SO IT LED US TO SEARCH OF MORE PROMISING OPTION
• Autologous Chondrocyte Implantation (ACI) BACKGROUND
• Identifying a Carticelreg Patient
• Identifying a Carticelreg Patienthelliphellip
• Pre-requisite for surgery
• Autologous Chondrocyte Implantation (ACI)
• Techniques
• ACIMACI Generic Method
• Slide 23
• Treatment with CARTICEL
• CARTICEL Manufacturing and Delivery
• Step 2 Implantation
• CARTICEL Implantation
• Periosteal Patch
• Slide 29
• Slide 30
• Aci steps summarised
• Slide 32
• Complications
• Slide 34
• Slide 35
• FOLLOW UP Biopsy
• FOLLOW UP MRI
• FOLLOW UP ARTHROSCOPIC
• Rehabilitation guidelines
• ACI Rehabilitation
• ACI Rehabilitation (2)
• COMPARISON WITH OTHER METHODS OF TREATMENTS
• COMPARISON WITH OTHER METHODS OF TREATMENTShelliphelliphellip
• COMPARISON WITH OTHER METHODS OF TREATMENTShelliphelliphellip (2)
• CONCLUSIONS
• Slide 46
• Recent advancesHYAFF 3D matrix
• HYAFF-based Scaffold
• CHONDRONtrade
• RECOVERY TO
• Slide 51

TREATMENT WITH CARTICEL

Uses your own cartilage cells (chondrocytes) to repair the articular cartilage damage in your knee When implanted into a cartilage injury your own cells can form new cartilage this new cartilage is very similar to your original cartilage The CARTICEL implantation procedure is called Autologous Chondrocyte Implantation or ACI It is a two-step process

Knee Cartilage Arthroscopy and BiopsyDuring an arthroscopic procedure surgeon assesses the extent of cartilage damage amp pt as a candidate for CARTICEL implantation

ldquoBiopsyrdquo of healthy tissue about the size of a pencil eraser ie about 200 -300 mg

From outer edge of sup Med or lat Femoral condyle or inner edge of lat Femoral condyle at the intercondylar notch

This sample is sent to product labs

Step 1 Biopsy

Biopsy can be stored for up to two years so you can schedule your surgery at your convenience

When you are ready your cells are cultured over three to five weeks they increase to approx 12 million cells in a vial containing 03 ndash 04 cc of medium Every step of the manufacturing process is monitored to ensure high quality and safety

CARTICEL MANUFACTURING AND DELIVERY

STEP 2 IMPLANTATION

Cartilage Injury CleanedDuring this second stage arthrotomy done to expose knee and any dead or damaged tissue from the injury removed with curette leaving only healthy tissue

Biomachenical allignment procedures if required should be done in conjunction with implantation

CARTICEL IMPLANTATION

PERIOSTEAL PATCH

surgeon takes a small piece of tissue from your shin bone and sews it securely over the injury

CARTICEL Implantation surgeon injects CARTICEL under the patch

When CARTICEL is surgically implanted into a cartilage injury it can grow and form new hyaline-like cartilage with properties similar to those of the original cartilage

Repairing the injury helps to reduce pain and improve movement and function

ACI STEPS summarised

MACI METHOD

Cultured chondrocytes seeded in bilayered typeIIII collagen membrane

Implanted using fibrin glue

Matrix remodelled in months replaced by extracellular matrix regenerate

The overall failure rate is at present quoted as being 10 The two most common complications include bullloosening of the transplant tissue bullformation of fibrous tissue at the repair site and adhesions with return of pain and locking Neither of these complications usually leaves the patient in a worse condition than hisher pre-transplantation state

Other adverse events include bullpost-op haematoma (big blood clot)bullhypertrophic synovitis (angry knee) and superficial wound infection

COMPLICATIONS

IMPROVEMENTS IN CLINICAL OUTCOME

ASSESMENT OF TECHNIQUE

FOLLOW UP RESULTS

ONE YEAR ASSESSMENT

Radiographs Alignment Bone quality

MRI Healing

cartilage Graft failure

Arthroscopy + probe Graft integrity Pressure biopsy

FOLLOW UP BIOPSY

FOLLOW UP MRI

Final appearance of theperiosteum sutured overfemoral condyle defect Thecartilage cells have beeninjected under the flap and thefinal suture placed to close thecover and provide a watertightseal

FOLLOW UP ARTHROSCOPIC

Arthroscopic appearance of thesame area 12 months afterCarticeltrade implantation Thedefect is no longer visible andthere is now hyaline cartilage(biopsy proven) filling theoriginal defect site

REHABILITATION GUIDELINES

Immobilization first 12-24 hours

(CPM) after 12-24 hours for about 4 weeks

Complete joint loading from about 5th week trochleapatellafrom about 8th week condyle Back to sports Low impact rarr within 6 monthsRepeated impact rarr from 8th monthHigh impact rarr from 10-12th month

ACI REHABILITATION

Weight bearingIt is recommended to keep you in non-weight bearing until the second week after surgery (ACI) You can increase the weight bearing gradually and you may be able to sustain your full weight bearing after 6 to 12 weeks from surgery

Range of motionRecovery on your ROM (Range of Motion) is gradually increased with a continuous passive motion (CPM) machine and may be completed to 140 degrees of ROM at 6 weeks to 12 weeks after surgery

ACI REHABILITATIONIndoor exerciseYou can strenghthen your muscles surrounding the knee joint with a four point exercise as well as isometric hamstring and squatting exercises from 4 weeks to 6 weeks after surgeryYou may start performing stationary bike activity without resistance and increase the resistance gradually

Outdoor exerciseAt 13 weeks after surgery you can start walking lightly and at 10 months after surgery you can perform jogging and then you may enjoy intensity exercise like playing tennis or volleyball from 18 months after surgery

Rehabilitation Goals at 12 weeks after ACIFull ROM (Range of Motion) Minimal edema level Minimal occasional pain Pain free tolerance to transitional phase exercise with adequate stability and motor control

COMPARISON WITH OTHER METHODS OF TREATMENTS

Autologous Chondrocyte Implantation Aims to increase the best condition for cartilage defectAdvantagesbullHyaline cartilage is formed bullPermanent reconstructed cartilage tissue bullMost valuable treatment

bullWith Fourth Generation ACI Use of cell ndash gel mixture (collagen hyaluronic acid and fibrin) has fast gelling properties (1 ndash 5 min) upon transplantation bullNo membrane or periosteal patch bullMinimal surgical exposure and reduced surgery time bullCorrects evenly irregular defect shapes bullApplicable to larger defects

COMPARISON WITH OTHER METHODS OF TREATMENTShelliphelliphellip

Abrasion arthroplastyAims to decrease the inflammation of the jointDisadvantagesbullRemoves many cartilage fragments from the jointbullSymptoms reoccur within one year

Drilling and MicrofractureAims to generate a healing responseDisadvantagesbullThe healing response in inadequate bullNo hyaline cartilage is formed but rather fibrocartilage bullHas a limited lifespan of approximately one year bullRapid deterioration after such procedures can be expected

COMPARISON WITH OTHER METHODS OF TREATMENTShelliphelliphellip

Perichondral ResurfacingDisadvantagesbullIsolated cartilage defects are often too large to be covered byh perichondrum bullLong term follow-up of such procedures indicate that the implants undergo endochondral ossification

Synthetic Materials (ie Carbon Fiber Mesh)Disadvantagesbull It often results in fibrous tissue formation bullNot adequate biomechanically bullOften the cause for synovitis in the joints

Osteocartiloginous GraftsAims to reconstruct jointsDisadvantagesbullUnless fresh cartilage is transplanted the cartilage is dead bullFresh grafts are not commonly used as they inevitably carry a risk of disease transmission bullCyropreserved grafts can survive for many years but ultimately deteriorate

Results of the Carticeltrade procedure have been encouraging although it is not always successful An analysis was done of the US and Swedish registry of 153 consecutive patients undergoing this procedure with follow-up from 1 week to 94 months The following results were obtainedbull Patients with clinical improvement 85bull Good or Excellent results 42 bull Good or Excellent results at 2 yearspersisting at 5 years post-op 97

Thus a total of 85 of patients showed some or complete improvement with theimplantation technique The Carticel procedure demonstrated good durability at 5-10 years out

CONCLUSIONS

CONCLUSIONS ACI Vs MACI No current evidence to justify aggressive treatment of

asymptomatic lesions with ACIMACI

Patients with full thickness symptomatic defects do poorly if left untreated

ACI and MACI lead to significant improvement in objective and patient reported clinical outcome scores for up to ten years(even among those with previous failed marrow stimulation techniques)

MACI has a superior rate of clinical improvement in comparison to ACI

Repair tissue may remodel and improve in quality with time

ACI and MACI comparable at 6 years

RECENT ADVANCESHYAFF 3D MATRIX

HYAFF biomaterialscontain high quantities ofderivatized HA

HA-richchondrocyte compatibleembryonic-like mileuconductive to regenerativehealing patterns

bull Non woven felt 2 mm thick fiber diameter 10 micronsbull Chondrocytes are isolated and passaged in culture on plasticdishes up to 3 weeksbull Cells are seeded for 2 weeks on HYAFF scaffold at a density of1 x 106 cm2 resulting in a total of 4 x 106 cm2 seeded cells pergraft

HYAFF-BASED SCAFFOLD

CHONDRONtrade

Uses a cell ndash gel mixture (includes collagen hyaluronic acid and fibrin) that has fast gelling properties (1 ndash 5 min) upon transplantation

This cell and gel mixture enable even cell distribution three-dimensionally moldable to fit irregular defect shape and applicable to a larger defectThus there is minimal surgical exposure and reduced surgery time

(three-dimensional reconstruction of a chondron from the growth plate of the murine long bone the model was generated from multiple sections imaged in an electron microscope plasma membranes are coloured green and internal organelles are visible within the top cell)

RECOVERY TO

HEALTHY ACTIVE LIFE

THANK YOU

• journal club (22-10-09)
• topic autologus chondrocyte implantation
• THE ROLE OF AUTOLOGOUS CHONDROCYTE IMPLANTATION (ACI) IN THE TR
• Slide 4
• AUTOLOGOUS CHONDROCYTE GRAFTS MULTICENTRIC TRIAL WITH 28 KNEE
• Slide 6
• Slide 7
• Articular Cartilage
• Hyaline Cartilage Structure 1048715The ldquostuffrdquo of cartilage
• Slide 11
• Cartilage Injury Occurs in Many Forms
• Articular Cartilage Defects a treatment challenge
• AND WHAT IS IN OUR BASKET
• SO IT LED US TO SEARCH OF MORE PROMISING OPTION
• Autologous Chondrocyte Implantation (ACI) BACKGROUND
• Identifying a Carticelreg Patient
• Identifying a Carticelreg Patienthelliphellip
• Pre-requisite for surgery
• Autologous Chondrocyte Implantation (ACI)
• Techniques
• ACIMACI Generic Method
• Slide 23
• Treatment with CARTICEL
• CARTICEL Manufacturing and Delivery
• Step 2 Implantation
• CARTICEL Implantation
• Periosteal Patch
• Slide 29
• Slide 30
• Aci steps summarised
• Slide 32
• Complications
• Slide 34
• Slide 35
• FOLLOW UP Biopsy
• FOLLOW UP MRI
• FOLLOW UP ARTHROSCOPIC
• Rehabilitation guidelines
• ACI Rehabilitation
• ACI Rehabilitation (2)
• COMPARISON WITH OTHER METHODS OF TREATMENTS
• COMPARISON WITH OTHER METHODS OF TREATMENTShelliphelliphellip
• COMPARISON WITH OTHER METHODS OF TREATMENTShelliphelliphellip (2)
• CONCLUSIONS
• Slide 46
• Recent advancesHYAFF 3D matrix
• HYAFF-based Scaffold
• CHONDRONtrade
• RECOVERY TO
• Slide 51

Biopsy can be stored for up to two years so you can schedule your surgery at your convenience

When you are ready your cells are cultured over three to five weeks they increase to approx 12 million cells in a vial containing 03 ndash 04 cc of medium Every step of the manufacturing process is monitored to ensure high quality and safety

CARTICEL MANUFACTURING AND DELIVERY

STEP 2 IMPLANTATION

Cartilage Injury CleanedDuring this second stage arthrotomy done to expose knee and any dead or damaged tissue from the injury removed with curette leaving only healthy tissue

Biomachenical allignment procedures if required should be done in conjunction with implantation

CARTICEL IMPLANTATION

PERIOSTEAL PATCH

surgeon takes a small piece of tissue from your shin bone and sews it securely over the injury

CARTICEL Implantation surgeon injects CARTICEL under the patch

When CARTICEL is surgically implanted into a cartilage injury it can grow and form new hyaline-like cartilage with properties similar to those of the original cartilage

Repairing the injury helps to reduce pain and improve movement and function

ACI STEPS summarised

MACI METHOD

Cultured chondrocytes seeded in bilayered typeIIII collagen membrane

Implanted using fibrin glue

Matrix remodelled in months replaced by extracellular matrix regenerate

The overall failure rate is at present quoted as being 10 The two most common complications include bullloosening of the transplant tissue bullformation of fibrous tissue at the repair site and adhesions with return of pain and locking Neither of these complications usually leaves the patient in a worse condition than hisher pre-transplantation state

Other adverse events include bullpost-op haematoma (big blood clot)bullhypertrophic synovitis (angry knee) and superficial wound infection

COMPLICATIONS

IMPROVEMENTS IN CLINICAL OUTCOME

ASSESMENT OF TECHNIQUE

FOLLOW UP RESULTS

ONE YEAR ASSESSMENT

Radiographs Alignment Bone quality

MRI Healing

cartilage Graft failure

Arthroscopy + probe Graft integrity Pressure biopsy

FOLLOW UP BIOPSY

FOLLOW UP MRI

Final appearance of theperiosteum sutured overfemoral condyle defect Thecartilage cells have beeninjected under the flap and thefinal suture placed to close thecover and provide a watertightseal

FOLLOW UP ARTHROSCOPIC

Arthroscopic appearance of thesame area 12 months afterCarticeltrade implantation Thedefect is no longer visible andthere is now hyaline cartilage(biopsy proven) filling theoriginal defect site

REHABILITATION GUIDELINES

Immobilization first 12-24 hours

(CPM) after 12-24 hours for about 4 weeks

Complete joint loading from about 5th week trochleapatellafrom about 8th week condyle Back to sports Low impact rarr within 6 monthsRepeated impact rarr from 8th monthHigh impact rarr from 10-12th month

ACI REHABILITATION

Weight bearingIt is recommended to keep you in non-weight bearing until the second week after surgery (ACI) You can increase the weight bearing gradually and you may be able to sustain your full weight bearing after 6 to 12 weeks from surgery

Range of motionRecovery on your ROM (Range of Motion) is gradually increased with a continuous passive motion (CPM) machine and may be completed to 140 degrees of ROM at 6 weeks to 12 weeks after surgery

ACI REHABILITATIONIndoor exerciseYou can strenghthen your muscles surrounding the knee joint with a four point exercise as well as isometric hamstring and squatting exercises from 4 weeks to 6 weeks after surgeryYou may start performing stationary bike activity without resistance and increase the resistance gradually

Outdoor exerciseAt 13 weeks after surgery you can start walking lightly and at 10 months after surgery you can perform jogging and then you may enjoy intensity exercise like playing tennis or volleyball from 18 months after surgery

Rehabilitation Goals at 12 weeks after ACIFull ROM (Range of Motion) Minimal edema level Minimal occasional pain Pain free tolerance to transitional phase exercise with adequate stability and motor control

COMPARISON WITH OTHER METHODS OF TREATMENTS

Autologous Chondrocyte Implantation Aims to increase the best condition for cartilage defectAdvantagesbullHyaline cartilage is formed bullPermanent reconstructed cartilage tissue bullMost valuable treatment

bullWith Fourth Generation ACI Use of cell ndash gel mixture (collagen hyaluronic acid and fibrin) has fast gelling properties (1 ndash 5 min) upon transplantation bullNo membrane or periosteal patch bullMinimal surgical exposure and reduced surgery time bullCorrects evenly irregular defect shapes bullApplicable to larger defects

COMPARISON WITH OTHER METHODS OF TREATMENTShelliphelliphellip

Abrasion arthroplastyAims to decrease the inflammation of the jointDisadvantagesbullRemoves many cartilage fragments from the jointbullSymptoms reoccur within one year

Drilling and MicrofractureAims to generate a healing responseDisadvantagesbullThe healing response in inadequate bullNo hyaline cartilage is formed but rather fibrocartilage bullHas a limited lifespan of approximately one year bullRapid deterioration after such procedures can be expected

COMPARISON WITH OTHER METHODS OF TREATMENTShelliphelliphellip

Perichondral ResurfacingDisadvantagesbullIsolated cartilage defects are often too large to be covered byh perichondrum bullLong term follow-up of such procedures indicate that the implants undergo endochondral ossification

Synthetic Materials (ie Carbon Fiber Mesh)Disadvantagesbull It often results in fibrous tissue formation bullNot adequate biomechanically bullOften the cause for synovitis in the joints

Osteocartiloginous GraftsAims to reconstruct jointsDisadvantagesbullUnless fresh cartilage is transplanted the cartilage is dead bullFresh grafts are not commonly used as they inevitably carry a risk of disease transmission bullCyropreserved grafts can survive for many years but ultimately deteriorate

Results of the Carticeltrade procedure have been encouraging although it is not always successful An analysis was done of the US and Swedish registry of 153 consecutive patients undergoing this procedure with follow-up from 1 week to 94 months The following results were obtainedbull Patients with clinical improvement 85bull Good or Excellent results 42 bull Good or Excellent results at 2 yearspersisting at 5 years post-op 97

Thus a total of 85 of patients showed some or complete improvement with theimplantation technique The Carticel procedure demonstrated good durability at 5-10 years out

CONCLUSIONS

CONCLUSIONS ACI Vs MACI No current evidence to justify aggressive treatment of

asymptomatic lesions with ACIMACI

Patients with full thickness symptomatic defects do poorly if left untreated

ACI and MACI lead to significant improvement in objective and patient reported clinical outcome scores for up to ten years(even among those with previous failed marrow stimulation techniques)

MACI has a superior rate of clinical improvement in comparison to ACI

Repair tissue may remodel and improve in quality with time

ACI and MACI comparable at 6 years

RECENT ADVANCESHYAFF 3D MATRIX

HYAFF biomaterialscontain high quantities ofderivatized HA

HA-richchondrocyte compatibleembryonic-like mileuconductive to regenerativehealing patterns

bull Non woven felt 2 mm thick fiber diameter 10 micronsbull Chondrocytes are isolated and passaged in culture on plasticdishes up to 3 weeksbull Cells are seeded for 2 weeks on HYAFF scaffold at a density of1 x 106 cm2 resulting in a total of 4 x 106 cm2 seeded cells pergraft

HYAFF-BASED SCAFFOLD

CHONDRONtrade

Uses a cell ndash gel mixture (includes collagen hyaluronic acid and fibrin) that has fast gelling properties (1 ndash 5 min) upon transplantation

This cell and gel mixture enable even cell distribution three-dimensionally moldable to fit irregular defect shape and applicable to a larger defectThus there is minimal surgical exposure and reduced surgery time

(three-dimensional reconstruction of a chondron from the growth plate of the murine long bone the model was generated from multiple sections imaged in an electron microscope plasma membranes are coloured green and internal organelles are visible within the top cell)

RECOVERY TO

HEALTHY ACTIVE LIFE

THANK YOU

• journal club (22-10-09)
• topic autologus chondrocyte implantation
• THE ROLE OF AUTOLOGOUS CHONDROCYTE IMPLANTATION (ACI) IN THE TR
• Slide 4
• AUTOLOGOUS CHONDROCYTE GRAFTS MULTICENTRIC TRIAL WITH 28 KNEE
• Slide 6
• Slide 7
• Articular Cartilage
• Hyaline Cartilage Structure 1048715The ldquostuffrdquo of cartilage
• Slide 11
• Cartilage Injury Occurs in Many Forms
• Articular Cartilage Defects a treatment challenge
• AND WHAT IS IN OUR BASKET
• SO IT LED US TO SEARCH OF MORE PROMISING OPTION
• Autologous Chondrocyte Implantation (ACI) BACKGROUND
• Identifying a Carticelreg Patient
• Identifying a Carticelreg Patienthelliphellip
• Pre-requisite for surgery
• Autologous Chondrocyte Implantation (ACI)
• Techniques
• ACIMACI Generic Method
• Slide 23
• Treatment with CARTICEL
• CARTICEL Manufacturing and Delivery
• Step 2 Implantation
• CARTICEL Implantation
• Periosteal Patch
• Slide 29
• Slide 30
• Aci steps summarised
• Slide 32
• Complications
• Slide 34
• Slide 35
• FOLLOW UP Biopsy
• FOLLOW UP MRI
• FOLLOW UP ARTHROSCOPIC
• Rehabilitation guidelines
• ACI Rehabilitation
• ACI Rehabilitation (2)
• COMPARISON WITH OTHER METHODS OF TREATMENTS
• COMPARISON WITH OTHER METHODS OF TREATMENTShelliphelliphellip
• COMPARISON WITH OTHER METHODS OF TREATMENTShelliphelliphellip (2)
• CONCLUSIONS
• Slide 46
• Recent advancesHYAFF 3D matrix
• HYAFF-based Scaffold
• CHONDRONtrade
• RECOVERY TO
• Slide 51

STEP 2 IMPLANTATION

Cartilage Injury CleanedDuring this second stage arthrotomy done to expose knee and any dead or damaged tissue from the injury removed with curette leaving only healthy tissue

Biomachenical allignment procedures if required should be done in conjunction with implantation

CARTICEL IMPLANTATION

PERIOSTEAL PATCH

surgeon takes a small piece of tissue from your shin bone and sews it securely over the injury

CARTICEL Implantation surgeon injects CARTICEL under the patch

When CARTICEL is surgically implanted into a cartilage injury it can grow and form new hyaline-like cartilage with properties similar to those of the original cartilage

Repairing the injury helps to reduce pain and improve movement and function

ACI STEPS summarised

MACI METHOD

Cultured chondrocytes seeded in bilayered typeIIII collagen membrane

Implanted using fibrin glue

Matrix remodelled in months replaced by extracellular matrix regenerate

The overall failure rate is at present quoted as being 10 The two most common complications include bullloosening of the transplant tissue bullformation of fibrous tissue at the repair site and adhesions with return of pain and locking Neither of these complications usually leaves the patient in a worse condition than hisher pre-transplantation state

Other adverse events include bullpost-op haematoma (big blood clot)bullhypertrophic synovitis (angry knee) and superficial wound infection

COMPLICATIONS

IMPROVEMENTS IN CLINICAL OUTCOME

ASSESMENT OF TECHNIQUE

FOLLOW UP RESULTS

ONE YEAR ASSESSMENT

Radiographs Alignment Bone quality

MRI Healing

cartilage Graft failure

Arthroscopy + probe Graft integrity Pressure biopsy

FOLLOW UP BIOPSY

FOLLOW UP MRI

Final appearance of theperiosteum sutured overfemoral condyle defect Thecartilage cells have beeninjected under the flap and thefinal suture placed to close thecover and provide a watertightseal

FOLLOW UP ARTHROSCOPIC

Arthroscopic appearance of thesame area 12 months afterCarticeltrade implantation Thedefect is no longer visible andthere is now hyaline cartilage(biopsy proven) filling theoriginal defect site

REHABILITATION GUIDELINES

Immobilization first 12-24 hours

(CPM) after 12-24 hours for about 4 weeks

Complete joint loading from about 5th week trochleapatellafrom about 8th week condyle Back to sports Low impact rarr within 6 monthsRepeated impact rarr from 8th monthHigh impact rarr from 10-12th month

ACI REHABILITATION

Weight bearingIt is recommended to keep you in non-weight bearing until the second week after surgery (ACI) You can increase the weight bearing gradually and you may be able to sustain your full weight bearing after 6 to 12 weeks from surgery

Range of motionRecovery on your ROM (Range of Motion) is gradually increased with a continuous passive motion (CPM) machine and may be completed to 140 degrees of ROM at 6 weeks to 12 weeks after surgery

ACI REHABILITATIONIndoor exerciseYou can strenghthen your muscles surrounding the knee joint with a four point exercise as well as isometric hamstring and squatting exercises from 4 weeks to 6 weeks after surgeryYou may start performing stationary bike activity without resistance and increase the resistance gradually

Outdoor exerciseAt 13 weeks after surgery you can start walking lightly and at 10 months after surgery you can perform jogging and then you may enjoy intensity exercise like playing tennis or volleyball from 18 months after surgery

Rehabilitation Goals at 12 weeks after ACIFull ROM (Range of Motion) Minimal edema level Minimal occasional pain Pain free tolerance to transitional phase exercise with adequate stability and motor control

COMPARISON WITH OTHER METHODS OF TREATMENTS

Autologous Chondrocyte Implantation Aims to increase the best condition for cartilage defectAdvantagesbullHyaline cartilage is formed bullPermanent reconstructed cartilage tissue bullMost valuable treatment

bullWith Fourth Generation ACI Use of cell ndash gel mixture (collagen hyaluronic acid and fibrin) has fast gelling properties (1 ndash 5 min) upon transplantation bullNo membrane or periosteal patch bullMinimal surgical exposure and reduced surgery time bullCorrects evenly irregular defect shapes bullApplicable to larger defects

COMPARISON WITH OTHER METHODS OF TREATMENTShelliphelliphellip

Abrasion arthroplastyAims to decrease the inflammation of the jointDisadvantagesbullRemoves many cartilage fragments from the jointbullSymptoms reoccur within one year

Drilling and MicrofractureAims to generate a healing responseDisadvantagesbullThe healing response in inadequate bullNo hyaline cartilage is formed but rather fibrocartilage bullHas a limited lifespan of approximately one year bullRapid deterioration after such procedures can be expected

COMPARISON WITH OTHER METHODS OF TREATMENTShelliphelliphellip

Perichondral ResurfacingDisadvantagesbullIsolated cartilage defects are often too large to be covered byh perichondrum bullLong term follow-up of such procedures indicate that the implants undergo endochondral ossification

Synthetic Materials (ie Carbon Fiber Mesh)Disadvantagesbull It often results in fibrous tissue formation bullNot adequate biomechanically bullOften the cause for synovitis in the joints

Osteocartiloginous GraftsAims to reconstruct jointsDisadvantagesbullUnless fresh cartilage is transplanted the cartilage is dead bullFresh grafts are not commonly used as they inevitably carry a risk of disease transmission bullCyropreserved grafts can survive for many years but ultimately deteriorate

Results of the Carticeltrade procedure have been encouraging although it is not always successful An analysis was done of the US and Swedish registry of 153 consecutive patients undergoing this procedure with follow-up from 1 week to 94 months The following results were obtainedbull Patients with clinical improvement 85bull Good or Excellent results 42 bull Good or Excellent results at 2 yearspersisting at 5 years post-op 97

Thus a total of 85 of patients showed some or complete improvement with theimplantation technique The Carticel procedure demonstrated good durability at 5-10 years out

CONCLUSIONS

CONCLUSIONS ACI Vs MACI No current evidence to justify aggressive treatment of

asymptomatic lesions with ACIMACI

Patients with full thickness symptomatic defects do poorly if left untreated

ACI and MACI lead to significant improvement in objective and patient reported clinical outcome scores for up to ten years(even among those with previous failed marrow stimulation techniques)

MACI has a superior rate of clinical improvement in comparison to ACI

Repair tissue may remodel and improve in quality with time

ACI and MACI comparable at 6 years

RECENT ADVANCESHYAFF 3D MATRIX

HYAFF biomaterialscontain high quantities ofderivatized HA

HA-richchondrocyte compatibleembryonic-like mileuconductive to regenerativehealing patterns

bull Non woven felt 2 mm thick fiber diameter 10 micronsbull Chondrocytes are isolated and passaged in culture on plasticdishes up to 3 weeksbull Cells are seeded for 2 weeks on HYAFF scaffold at a density of1 x 106 cm2 resulting in a total of 4 x 106 cm2 seeded cells pergraft

HYAFF-BASED SCAFFOLD

CHONDRONtrade

Uses a cell ndash gel mixture (includes collagen hyaluronic acid and fibrin) that has fast gelling properties (1 ndash 5 min) upon transplantation

This cell and gel mixture enable even cell distribution three-dimensionally moldable to fit irregular defect shape and applicable to a larger defectThus there is minimal surgical exposure and reduced surgery time

(three-dimensional reconstruction of a chondron from the growth plate of the murine long bone the model was generated from multiple sections imaged in an electron microscope plasma membranes are coloured green and internal organelles are visible within the top cell)

RECOVERY TO

HEALTHY ACTIVE LIFE

THANK YOU

• journal club (22-10-09)
• topic autologus chondrocyte implantation
• THE ROLE OF AUTOLOGOUS CHONDROCYTE IMPLANTATION (ACI) IN THE TR
• Slide 4
• AUTOLOGOUS CHONDROCYTE GRAFTS MULTICENTRIC TRIAL WITH 28 KNEE
• Slide 6
• Slide 7
• Articular Cartilage
• Hyaline Cartilage Structure 1048715The ldquostuffrdquo of cartilage
• Slide 11
• Cartilage Injury Occurs in Many Forms
• Articular Cartilage Defects a treatment challenge
• AND WHAT IS IN OUR BASKET
• SO IT LED US TO SEARCH OF MORE PROMISING OPTION
• Autologous Chondrocyte Implantation (ACI) BACKGROUND
• Identifying a Carticelreg Patient
• Identifying a Carticelreg Patienthelliphellip
• Pre-requisite for surgery
• Autologous Chondrocyte Implantation (ACI)
• Techniques
• ACIMACI Generic Method
• Slide 23
• Treatment with CARTICEL
• CARTICEL Manufacturing and Delivery
• Step 2 Implantation
• CARTICEL Implantation
• Periosteal Patch
• Slide 29
• Slide 30
• Aci steps summarised
• Slide 32
• Complications
• Slide 34
• Slide 35
• FOLLOW UP Biopsy
• FOLLOW UP MRI
• FOLLOW UP ARTHROSCOPIC
• Rehabilitation guidelines
• ACI Rehabilitation
• ACI Rehabilitation (2)
• COMPARISON WITH OTHER METHODS OF TREATMENTS
• COMPARISON WITH OTHER METHODS OF TREATMENTShelliphelliphellip
• COMPARISON WITH OTHER METHODS OF TREATMENTShelliphelliphellip (2)
• CONCLUSIONS
• Slide 46
• Recent advancesHYAFF 3D matrix
• HYAFF-based Scaffold
• CHONDRONtrade
• RECOVERY TO
• Slide 51

CARTICEL IMPLANTATION

PERIOSTEAL PATCH

surgeon takes a small piece of tissue from your shin bone and sews it securely over the injury

CARTICEL Implantation surgeon injects CARTICEL under the patch

When CARTICEL is surgically implanted into a cartilage injury it can grow and form new hyaline-like cartilage with properties similar to those of the original cartilage

Repairing the injury helps to reduce pain and improve movement and function

ACI STEPS summarised

MACI METHOD

Cultured chondrocytes seeded in bilayered typeIIII collagen membrane

Implanted using fibrin glue

Matrix remodelled in months replaced by extracellular matrix regenerate

The overall failure rate is at present quoted as being 10 The two most common complications include bullloosening of the transplant tissue bullformation of fibrous tissue at the repair site and adhesions with return of pain and locking Neither of these complications usually leaves the patient in a worse condition than hisher pre-transplantation state

Other adverse events include bullpost-op haematoma (big blood clot)bullhypertrophic synovitis (angry knee) and superficial wound infection

COMPLICATIONS

IMPROVEMENTS IN CLINICAL OUTCOME

ASSESMENT OF TECHNIQUE

FOLLOW UP RESULTS

ONE YEAR ASSESSMENT

Radiographs Alignment Bone quality

MRI Healing

cartilage Graft failure

Arthroscopy + probe Graft integrity Pressure biopsy

FOLLOW UP BIOPSY

FOLLOW UP MRI

Final appearance of theperiosteum sutured overfemoral condyle defect Thecartilage cells have beeninjected under the flap and thefinal suture placed to close thecover and provide a watertightseal

FOLLOW UP ARTHROSCOPIC

Arthroscopic appearance of thesame area 12 months afterCarticeltrade implantation Thedefect is no longer visible andthere is now hyaline cartilage(biopsy proven) filling theoriginal defect site

REHABILITATION GUIDELINES

Immobilization first 12-24 hours

(CPM) after 12-24 hours for about 4 weeks

Complete joint loading from about 5th week trochleapatellafrom about 8th week condyle Back to sports Low impact rarr within 6 monthsRepeated impact rarr from 8th monthHigh impact rarr from 10-12th month

ACI REHABILITATION

Weight bearingIt is recommended to keep you in non-weight bearing until the second week after surgery (ACI) You can increase the weight bearing gradually and you may be able to sustain your full weight bearing after 6 to 12 weeks from surgery

Range of motionRecovery on your ROM (Range of Motion) is gradually increased with a continuous passive motion (CPM) machine and may be completed to 140 degrees of ROM at 6 weeks to 12 weeks after surgery

ACI REHABILITATIONIndoor exerciseYou can strenghthen your muscles surrounding the knee joint with a four point exercise as well as isometric hamstring and squatting exercises from 4 weeks to 6 weeks after surgeryYou may start performing stationary bike activity without resistance and increase the resistance gradually

Outdoor exerciseAt 13 weeks after surgery you can start walking lightly and at 10 months after surgery you can perform jogging and then you may enjoy intensity exercise like playing tennis or volleyball from 18 months after surgery

Rehabilitation Goals at 12 weeks after ACIFull ROM (Range of Motion) Minimal edema level Minimal occasional pain Pain free tolerance to transitional phase exercise with adequate stability and motor control

COMPARISON WITH OTHER METHODS OF TREATMENTS

Autologous Chondrocyte Implantation Aims to increase the best condition for cartilage defectAdvantagesbullHyaline cartilage is formed bullPermanent reconstructed cartilage tissue bullMost valuable treatment

bullWith Fourth Generation ACI Use of cell ndash gel mixture (collagen hyaluronic acid and fibrin) has fast gelling properties (1 ndash 5 min) upon transplantation bullNo membrane or periosteal patch bullMinimal surgical exposure and reduced surgery time bullCorrects evenly irregular defect shapes bullApplicable to larger defects

COMPARISON WITH OTHER METHODS OF TREATMENTShelliphelliphellip

Abrasion arthroplastyAims to decrease the inflammation of the jointDisadvantagesbullRemoves many cartilage fragments from the jointbullSymptoms reoccur within one year

Drilling and MicrofractureAims to generate a healing responseDisadvantagesbullThe healing response in inadequate bullNo hyaline cartilage is formed but rather fibrocartilage bullHas a limited lifespan of approximately one year bullRapid deterioration after such procedures can be expected

COMPARISON WITH OTHER METHODS OF TREATMENTShelliphelliphellip

Perichondral ResurfacingDisadvantagesbullIsolated cartilage defects are often too large to be covered byh perichondrum bullLong term follow-up of such procedures indicate that the implants undergo endochondral ossification

Synthetic Materials (ie Carbon Fiber Mesh)Disadvantagesbull It often results in fibrous tissue formation bullNot adequate biomechanically bullOften the cause for synovitis in the joints

Osteocartiloginous GraftsAims to reconstruct jointsDisadvantagesbullUnless fresh cartilage is transplanted the cartilage is dead bullFresh grafts are not commonly used as they inevitably carry a risk of disease transmission bullCyropreserved grafts can survive for many years but ultimately deteriorate

Results of the Carticeltrade procedure have been encouraging although it is not always successful An analysis was done of the US and Swedish registry of 153 consecutive patients undergoing this procedure with follow-up from 1 week to 94 months The following results were obtainedbull Patients with clinical improvement 85bull Good or Excellent results 42 bull Good or Excellent results at 2 yearspersisting at 5 years post-op 97

Thus a total of 85 of patients showed some or complete improvement with theimplantation technique The Carticel procedure demonstrated good durability at 5-10 years out

CONCLUSIONS

CONCLUSIONS ACI Vs MACI No current evidence to justify aggressive treatment of

asymptomatic lesions with ACIMACI

Patients with full thickness symptomatic defects do poorly if left untreated

ACI and MACI lead to significant improvement in objective and patient reported clinical outcome scores for up to ten years(even among those with previous failed marrow stimulation techniques)

MACI has a superior rate of clinical improvement in comparison to ACI

Repair tissue may remodel and improve in quality with time

ACI and MACI comparable at 6 years

RECENT ADVANCESHYAFF 3D MATRIX

HYAFF biomaterialscontain high quantities ofderivatized HA

HA-richchondrocyte compatibleembryonic-like mileuconductive to regenerativehealing patterns

bull Non woven felt 2 mm thick fiber diameter 10 micronsbull Chondrocytes are isolated and passaged in culture on plasticdishes up to 3 weeksbull Cells are seeded for 2 weeks on HYAFF scaffold at a density of1 x 106 cm2 resulting in a total of 4 x 106 cm2 seeded cells pergraft

HYAFF-BASED SCAFFOLD

CHONDRONtrade

Uses a cell ndash gel mixture (includes collagen hyaluronic acid and fibrin) that has fast gelling properties (1 ndash 5 min) upon transplantation

This cell and gel mixture enable even cell distribution three-dimensionally moldable to fit irregular defect shape and applicable to a larger defectThus there is minimal surgical exposure and reduced surgery time

(three-dimensional reconstruction of a chondron from the growth plate of the murine long bone the model was generated from multiple sections imaged in an electron microscope plasma membranes are coloured green and internal organelles are visible within the top cell)

RECOVERY TO

HEALTHY ACTIVE LIFE

THANK YOU

• journal club (22-10-09)
• topic autologus chondrocyte implantation
• THE ROLE OF AUTOLOGOUS CHONDROCYTE IMPLANTATION (ACI) IN THE TR
• Slide 4
• AUTOLOGOUS CHONDROCYTE GRAFTS MULTICENTRIC TRIAL WITH 28 KNEE
• Slide 6
• Slide 7
• Articular Cartilage
• Hyaline Cartilage Structure 1048715The ldquostuffrdquo of cartilage
• Slide 11
• Cartilage Injury Occurs in Many Forms
• Articular Cartilage Defects a treatment challenge
• AND WHAT IS IN OUR BASKET
• SO IT LED US TO SEARCH OF MORE PROMISING OPTION
• Autologous Chondrocyte Implantation (ACI) BACKGROUND
• Identifying a Carticelreg Patient
• Identifying a Carticelreg Patienthelliphellip
• Pre-requisite for surgery
• Autologous Chondrocyte Implantation (ACI)
• Techniques
• ACIMACI Generic Method
• Slide 23
• Treatment with CARTICEL
• CARTICEL Manufacturing and Delivery
• Step 2 Implantation
• CARTICEL Implantation
• Periosteal Patch
• Slide 29
• Slide 30
• Aci steps summarised
• Slide 32
• Complications
• Slide 34
• Slide 35
• FOLLOW UP Biopsy
• FOLLOW UP MRI
• FOLLOW UP ARTHROSCOPIC
• Rehabilitation guidelines
• ACI Rehabilitation
• ACI Rehabilitation (2)
• COMPARISON WITH OTHER METHODS OF TREATMENTS
• COMPARISON WITH OTHER METHODS OF TREATMENTShelliphelliphellip
• COMPARISON WITH OTHER METHODS OF TREATMENTShelliphelliphellip (2)
• CONCLUSIONS
• Slide 46
• Recent advancesHYAFF 3D matrix
• HYAFF-based Scaffold
• CHONDRONtrade
• RECOVERY TO
• Slide 51

PERIOSTEAL PATCH

surgeon takes a small piece of tissue from your shin bone and sews it securely over the injury

CARTICEL Implantation surgeon injects CARTICEL under the patch

When CARTICEL is surgically implanted into a cartilage injury it can grow and form new hyaline-like cartilage with properties similar to those of the original cartilage

Repairing the injury helps to reduce pain and improve movement and function

ACI STEPS summarised

MACI METHOD

Cultured chondrocytes seeded in bilayered typeIIII collagen membrane

Implanted using fibrin glue

Matrix remodelled in months replaced by extracellular matrix regenerate

The overall failure rate is at present quoted as being 10 The two most common complications include bullloosening of the transplant tissue bullformation of fibrous tissue at the repair site and adhesions with return of pain and locking Neither of these complications usually leaves the patient in a worse condition than hisher pre-transplantation state

Other adverse events include bullpost-op haematoma (big blood clot)bullhypertrophic synovitis (angry knee) and superficial wound infection

COMPLICATIONS

IMPROVEMENTS IN CLINICAL OUTCOME

ASSESMENT OF TECHNIQUE

FOLLOW UP RESULTS

ONE YEAR ASSESSMENT

Radiographs Alignment Bone quality

MRI Healing

cartilage Graft failure

Arthroscopy + probe Graft integrity Pressure biopsy

FOLLOW UP BIOPSY

FOLLOW UP MRI

Final appearance of theperiosteum sutured overfemoral condyle defect Thecartilage cells have beeninjected under the flap and thefinal suture placed to close thecover and provide a watertightseal

FOLLOW UP ARTHROSCOPIC

Arthroscopic appearance of thesame area 12 months afterCarticeltrade implantation Thedefect is no longer visible andthere is now hyaline cartilage(biopsy proven) filling theoriginal defect site

REHABILITATION GUIDELINES

Immobilization first 12-24 hours

(CPM) after 12-24 hours for about 4 weeks

Complete joint loading from about 5th week trochleapatellafrom about 8th week condyle Back to sports Low impact rarr within 6 monthsRepeated impact rarr from 8th monthHigh impact rarr from 10-12th month

ACI REHABILITATION

Weight bearingIt is recommended to keep you in non-weight bearing until the second week after surgery (ACI) You can increase the weight bearing gradually and you may be able to sustain your full weight bearing after 6 to 12 weeks from surgery

Range of motionRecovery on your ROM (Range of Motion) is gradually increased with a continuous passive motion (CPM) machine and may be completed to 140 degrees of ROM at 6 weeks to 12 weeks after surgery

ACI REHABILITATIONIndoor exerciseYou can strenghthen your muscles surrounding the knee joint with a four point exercise as well as isometric hamstring and squatting exercises from 4 weeks to 6 weeks after surgeryYou may start performing stationary bike activity without resistance and increase the resistance gradually

Outdoor exerciseAt 13 weeks after surgery you can start walking lightly and at 10 months after surgery you can perform jogging and then you may enjoy intensity exercise like playing tennis or volleyball from 18 months after surgery

Rehabilitation Goals at 12 weeks after ACIFull ROM (Range of Motion) Minimal edema level Minimal occasional pain Pain free tolerance to transitional phase exercise with adequate stability and motor control

COMPARISON WITH OTHER METHODS OF TREATMENTS

Autologous Chondrocyte Implantation Aims to increase the best condition for cartilage defectAdvantagesbullHyaline cartilage is formed bullPermanent reconstructed cartilage tissue bullMost valuable treatment

bullWith Fourth Generation ACI Use of cell ndash gel mixture (collagen hyaluronic acid and fibrin) has fast gelling properties (1 ndash 5 min) upon transplantation bullNo membrane or periosteal patch bullMinimal surgical exposure and reduced surgery time bullCorrects evenly irregular defect shapes bullApplicable to larger defects

COMPARISON WITH OTHER METHODS OF TREATMENTShelliphelliphellip

Abrasion arthroplastyAims to decrease the inflammation of the jointDisadvantagesbullRemoves many cartilage fragments from the jointbullSymptoms reoccur within one year

Drilling and MicrofractureAims to generate a healing responseDisadvantagesbullThe healing response in inadequate bullNo hyaline cartilage is formed but rather fibrocartilage bullHas a limited lifespan of approximately one year bullRapid deterioration after such procedures can be expected

COMPARISON WITH OTHER METHODS OF TREATMENTShelliphelliphellip

Perichondral ResurfacingDisadvantagesbullIsolated cartilage defects are often too large to be covered byh perichondrum bullLong term follow-up of such procedures indicate that the implants undergo endochondral ossification

Synthetic Materials (ie Carbon Fiber Mesh)Disadvantagesbull It often results in fibrous tissue formation bullNot adequate biomechanically bullOften the cause for synovitis in the joints

Osteocartiloginous GraftsAims to reconstruct jointsDisadvantagesbullUnless fresh cartilage is transplanted the cartilage is dead bullFresh grafts are not commonly used as they inevitably carry a risk of disease transmission bullCyropreserved grafts can survive for many years but ultimately deteriorate

Results of the Carticeltrade procedure have been encouraging although it is not always successful An analysis was done of the US and Swedish registry of 153 consecutive patients undergoing this procedure with follow-up from 1 week to 94 months The following results were obtainedbull Patients with clinical improvement 85bull Good or Excellent results 42 bull Good or Excellent results at 2 yearspersisting at 5 years post-op 97

Thus a total of 85 of patients showed some or complete improvement with theimplantation technique The Carticel procedure demonstrated good durability at 5-10 years out

CONCLUSIONS

CONCLUSIONS ACI Vs MACI No current evidence to justify aggressive treatment of

asymptomatic lesions with ACIMACI

Patients with full thickness symptomatic defects do poorly if left untreated

ACI and MACI lead to significant improvement in objective and patient reported clinical outcome scores for up to ten years(even among those with previous failed marrow stimulation techniques)

MACI has a superior rate of clinical improvement in comparison to ACI

Repair tissue may remodel and improve in quality with time

ACI and MACI comparable at 6 years

RECENT ADVANCESHYAFF 3D MATRIX

HYAFF biomaterialscontain high quantities ofderivatized HA

HA-richchondrocyte compatibleembryonic-like mileuconductive to regenerativehealing patterns

bull Non woven felt 2 mm thick fiber diameter 10 micronsbull Chondrocytes are isolated and passaged in culture on plasticdishes up to 3 weeksbull Cells are seeded for 2 weeks on HYAFF scaffold at a density of1 x 106 cm2 resulting in a total of 4 x 106 cm2 seeded cells pergraft

HYAFF-BASED SCAFFOLD

CHONDRONtrade

Uses a cell ndash gel mixture (includes collagen hyaluronic acid and fibrin) that has fast gelling properties (1 ndash 5 min) upon transplantation

This cell and gel mixture enable even cell distribution three-dimensionally moldable to fit irregular defect shape and applicable to a larger defectThus there is minimal surgical exposure and reduced surgery time

(three-dimensional reconstruction of a chondron from the growth plate of the murine long bone the model was generated from multiple sections imaged in an electron microscope plasma membranes are coloured green and internal organelles are visible within the top cell)

RECOVERY TO

HEALTHY ACTIVE LIFE

THANK YOU

• journal club (22-10-09)
• topic autologus chondrocyte implantation
• THE ROLE OF AUTOLOGOUS CHONDROCYTE IMPLANTATION (ACI) IN THE TR
• Slide 4
• AUTOLOGOUS CHONDROCYTE GRAFTS MULTICENTRIC TRIAL WITH 28 KNEE
• Slide 6
• Slide 7
• Articular Cartilage
• Hyaline Cartilage Structure 1048715The ldquostuffrdquo of cartilage
• Slide 11
• Cartilage Injury Occurs in Many Forms
• Articular Cartilage Defects a treatment challenge
• AND WHAT IS IN OUR BASKET
• SO IT LED US TO SEARCH OF MORE PROMISING OPTION
• Autologous Chondrocyte Implantation (ACI) BACKGROUND
• Identifying a Carticelreg Patient
• Identifying a Carticelreg Patienthelliphellip
• Pre-requisite for surgery
• Autologous Chondrocyte Implantation (ACI)
• Techniques
• ACIMACI Generic Method
• Slide 23
• Treatment with CARTICEL
• CARTICEL Manufacturing and Delivery
• Step 2 Implantation
• CARTICEL Implantation
• Periosteal Patch
• Slide 29
• Slide 30
• Aci steps summarised
• Slide 32
• Complications
• Slide 34
• Slide 35
• FOLLOW UP Biopsy
• FOLLOW UP MRI
• FOLLOW UP ARTHROSCOPIC
• Rehabilitation guidelines
• ACI Rehabilitation
• ACI Rehabilitation (2)
• COMPARISON WITH OTHER METHODS OF TREATMENTS
• COMPARISON WITH OTHER METHODS OF TREATMENTShelliphelliphellip
• COMPARISON WITH OTHER METHODS OF TREATMENTShelliphelliphellip (2)
• CONCLUSIONS
• Slide 46
• Recent advancesHYAFF 3D matrix
• HYAFF-based Scaffold
• CHONDRONtrade
• RECOVERY TO
• Slide 51

ACI STEPS summarised

MACI METHOD

Cultured chondrocytes seeded in bilayered typeIIII collagen membrane

Implanted using fibrin glue

Matrix remodelled in months replaced by extracellular matrix regenerate

The overall failure rate is at present quoted as being 10 The two most common complications include bullloosening of the transplant tissue bullformation of fibrous tissue at the repair site and adhesions with return of pain and locking Neither of these complications usually leaves the patient in a worse condition than hisher pre-transplantation state

Other adverse events include bullpost-op haematoma (big blood clot)bullhypertrophic synovitis (angry knee) and superficial wound infection

COMPLICATIONS

IMPROVEMENTS IN CLINICAL OUTCOME

ASSESMENT OF TECHNIQUE

FOLLOW UP RESULTS

ONE YEAR ASSESSMENT

Radiographs Alignment Bone quality

MRI Healing

cartilage Graft failure

Arthroscopy + probe Graft integrity Pressure biopsy

FOLLOW UP BIOPSY

FOLLOW UP MRI

Final appearance of theperiosteum sutured overfemoral condyle defect Thecartilage cells have beeninjected under the flap and thefinal suture placed to close thecover and provide a watertightseal

FOLLOW UP ARTHROSCOPIC

Arthroscopic appearance of thesame area 12 months afterCarticeltrade implantation Thedefect is no longer visible andthere is now hyaline cartilage(biopsy proven) filling theoriginal defect site

REHABILITATION GUIDELINES

Immobilization first 12-24 hours

(CPM) after 12-24 hours for about 4 weeks

Complete joint loading from about 5th week trochleapatellafrom about 8th week condyle Back to sports Low impact rarr within 6 monthsRepeated impact rarr from 8th monthHigh impact rarr from 10-12th month

ACI REHABILITATION

Weight bearingIt is recommended to keep you in non-weight bearing until the second week after surgery (ACI) You can increase the weight bearing gradually and you may be able to sustain your full weight bearing after 6 to 12 weeks from surgery

Range of motionRecovery on your ROM (Range of Motion) is gradually increased with a continuous passive motion (CPM) machine and may be completed to 140 degrees of ROM at 6 weeks to 12 weeks after surgery

ACI REHABILITATIONIndoor exerciseYou can strenghthen your muscles surrounding the knee joint with a four point exercise as well as isometric hamstring and squatting exercises from 4 weeks to 6 weeks after surgeryYou may start performing stationary bike activity without resistance and increase the resistance gradually

Outdoor exerciseAt 13 weeks after surgery you can start walking lightly and at 10 months after surgery you can perform jogging and then you may enjoy intensity exercise like playing tennis or volleyball from 18 months after surgery

Rehabilitation Goals at 12 weeks after ACIFull ROM (Range of Motion) Minimal edema level Minimal occasional pain Pain free tolerance to transitional phase exercise with adequate stability and motor control

COMPARISON WITH OTHER METHODS OF TREATMENTS

Autologous Chondrocyte Implantation Aims to increase the best condition for cartilage defectAdvantagesbullHyaline cartilage is formed bullPermanent reconstructed cartilage tissue bullMost valuable treatment

bullWith Fourth Generation ACI Use of cell ndash gel mixture (collagen hyaluronic acid and fibrin) has fast gelling properties (1 ndash 5 min) upon transplantation bullNo membrane or periosteal patch bullMinimal surgical exposure and reduced surgery time bullCorrects evenly irregular defect shapes bullApplicable to larger defects

COMPARISON WITH OTHER METHODS OF TREATMENTShelliphelliphellip

Abrasion arthroplastyAims to decrease the inflammation of the jointDisadvantagesbullRemoves many cartilage fragments from the jointbullSymptoms reoccur within one year

Drilling and MicrofractureAims to generate a healing responseDisadvantagesbullThe healing response in inadequate bullNo hyaline cartilage is formed but rather fibrocartilage bullHas a limited lifespan of approximately one year bullRapid deterioration after such procedures can be expected

COMPARISON WITH OTHER METHODS OF TREATMENTShelliphelliphellip

Perichondral ResurfacingDisadvantagesbullIsolated cartilage defects are often too large to be covered byh perichondrum bullLong term follow-up of such procedures indicate that the implants undergo endochondral ossification

Synthetic Materials (ie Carbon Fiber Mesh)Disadvantagesbull It often results in fibrous tissue formation bullNot adequate biomechanically bullOften the cause for synovitis in the joints

Osteocartiloginous GraftsAims to reconstruct jointsDisadvantagesbullUnless fresh cartilage is transplanted the cartilage is dead bullFresh grafts are not commonly used as they inevitably carry a risk of disease transmission bullCyropreserved grafts can survive for many years but ultimately deteriorate

Results of the Carticeltrade procedure have been encouraging although it is not always successful An analysis was done of the US and Swedish registry of 153 consecutive patients undergoing this procedure with follow-up from 1 week to 94 months The following results were obtainedbull Patients with clinical improvement 85bull Good or Excellent results 42 bull Good or Excellent results at 2 yearspersisting at 5 years post-op 97

Thus a total of 85 of patients showed some or complete improvement with theimplantation technique The Carticel procedure demonstrated good durability at 5-10 years out

CONCLUSIONS

CONCLUSIONS ACI Vs MACI No current evidence to justify aggressive treatment of

asymptomatic lesions with ACIMACI

Patients with full thickness symptomatic defects do poorly if left untreated

ACI and MACI lead to significant improvement in objective and patient reported clinical outcome scores for up to ten years(even among those with previous failed marrow stimulation techniques)

MACI has a superior rate of clinical improvement in comparison to ACI

Repair tissue may remodel and improve in quality with time

ACI and MACI comparable at 6 years

RECENT ADVANCESHYAFF 3D MATRIX

HYAFF biomaterialscontain high quantities ofderivatized HA

HA-richchondrocyte compatibleembryonic-like mileuconductive to regenerativehealing patterns

bull Non woven felt 2 mm thick fiber diameter 10 micronsbull Chondrocytes are isolated and passaged in culture on plasticdishes up to 3 weeksbull Cells are seeded for 2 weeks on HYAFF scaffold at a density of1 x 106 cm2 resulting in a total of 4 x 106 cm2 seeded cells pergraft

HYAFF-BASED SCAFFOLD

CHONDRONtrade

Uses a cell ndash gel mixture (includes collagen hyaluronic acid and fibrin) that has fast gelling properties (1 ndash 5 min) upon transplantation

This cell and gel mixture enable even cell distribution three-dimensionally moldable to fit irregular defect shape and applicable to a larger defectThus there is minimal surgical exposure and reduced surgery time

(three-dimensional reconstruction of a chondron from the growth plate of the murine long bone the model was generated from multiple sections imaged in an electron microscope plasma membranes are coloured green and internal organelles are visible within the top cell)

RECOVERY TO

HEALTHY ACTIVE LIFE

THANK YOU

• journal club (22-10-09)
• topic autologus chondrocyte implantation
• THE ROLE OF AUTOLOGOUS CHONDROCYTE IMPLANTATION (ACI) IN THE TR
• Slide 4
• AUTOLOGOUS CHONDROCYTE GRAFTS MULTICENTRIC TRIAL WITH 28 KNEE
• Slide 6
• Slide 7
• Articular Cartilage
• Hyaline Cartilage Structure 1048715The ldquostuffrdquo of cartilage
• Slide 11
• Cartilage Injury Occurs in Many Forms
• Articular Cartilage Defects a treatment challenge
• AND WHAT IS IN OUR BASKET
• SO IT LED US TO SEARCH OF MORE PROMISING OPTION
• Autologous Chondrocyte Implantation (ACI) BACKGROUND
• Identifying a Carticelreg Patient
• Identifying a Carticelreg Patienthelliphellip
• Pre-requisite for surgery
• Autologous Chondrocyte Implantation (ACI)
• Techniques
• ACIMACI Generic Method
• Slide 23
• Treatment with CARTICEL
• CARTICEL Manufacturing and Delivery
• Step 2 Implantation
• CARTICEL Implantation
• Periosteal Patch
• Slide 29
• Slide 30
• Aci steps summarised
• Slide 32
• Complications
• Slide 34
• Slide 35
• FOLLOW UP Biopsy
• FOLLOW UP MRI
• FOLLOW UP ARTHROSCOPIC
• Rehabilitation guidelines
• ACI Rehabilitation
• ACI Rehabilitation (2)
• COMPARISON WITH OTHER METHODS OF TREATMENTS
• COMPARISON WITH OTHER METHODS OF TREATMENTShelliphelliphellip
• COMPARISON WITH OTHER METHODS OF TREATMENTShelliphelliphellip (2)
• CONCLUSIONS
• Slide 46
• Recent advancesHYAFF 3D matrix
• HYAFF-based Scaffold
• CHONDRONtrade
• RECOVERY TO
• Slide 51

MACI METHOD

Cultured chondrocytes seeded in bilayered typeIIII collagen membrane

Implanted using fibrin glue

Matrix remodelled in months replaced by extracellular matrix regenerate

The overall failure rate is at present quoted as being 10 The two most common complications include bullloosening of the transplant tissue bullformation of fibrous tissue at the repair site and adhesions with return of pain and locking Neither of these complications usually leaves the patient in a worse condition than hisher pre-transplantation state

Other adverse events include bullpost-op haematoma (big blood clot)bullhypertrophic synovitis (angry knee) and superficial wound infection

COMPLICATIONS

IMPROVEMENTS IN CLINICAL OUTCOME

ASSESMENT OF TECHNIQUE

FOLLOW UP RESULTS

ONE YEAR ASSESSMENT

Radiographs Alignment Bone quality

MRI Healing

cartilage Graft failure

Arthroscopy + probe Graft integrity Pressure biopsy

FOLLOW UP BIOPSY

FOLLOW UP MRI

Final appearance of theperiosteum sutured overfemoral condyle defect Thecartilage cells have beeninjected under the flap and thefinal suture placed to close thecover and provide a watertightseal

FOLLOW UP ARTHROSCOPIC

Arthroscopic appearance of thesame area 12 months afterCarticeltrade implantation Thedefect is no longer visible andthere is now hyaline cartilage(biopsy proven) filling theoriginal defect site

REHABILITATION GUIDELINES

Immobilization first 12-24 hours

(CPM) after 12-24 hours for about 4 weeks

Complete joint loading from about 5th week trochleapatellafrom about 8th week condyle Back to sports Low impact rarr within 6 monthsRepeated impact rarr from 8th monthHigh impact rarr from 10-12th month

ACI REHABILITATION

Weight bearingIt is recommended to keep you in non-weight bearing until the second week after surgery (ACI) You can increase the weight bearing gradually and you may be able to sustain your full weight bearing after 6 to 12 weeks from surgery

Range of motionRecovery on your ROM (Range of Motion) is gradually increased with a continuous passive motion (CPM) machine and may be completed to 140 degrees of ROM at 6 weeks to 12 weeks after surgery

ACI REHABILITATIONIndoor exerciseYou can strenghthen your muscles surrounding the knee joint with a four point exercise as well as isometric hamstring and squatting exercises from 4 weeks to 6 weeks after surgeryYou may start performing stationary bike activity without resistance and increase the resistance gradually

Outdoor exerciseAt 13 weeks after surgery you can start walking lightly and at 10 months after surgery you can perform jogging and then you may enjoy intensity exercise like playing tennis or volleyball from 18 months after surgery

Rehabilitation Goals at 12 weeks after ACIFull ROM (Range of Motion) Minimal edema level Minimal occasional pain Pain free tolerance to transitional phase exercise with adequate stability and motor control

COMPARISON WITH OTHER METHODS OF TREATMENTS

Autologous Chondrocyte Implantation Aims to increase the best condition for cartilage defectAdvantagesbullHyaline cartilage is formed bullPermanent reconstructed cartilage tissue bullMost valuable treatment

bullWith Fourth Generation ACI Use of cell ndash gel mixture (collagen hyaluronic acid and fibrin) has fast gelling properties (1 ndash 5 min) upon transplantation bullNo membrane or periosteal patch bullMinimal surgical exposure and reduced surgery time bullCorrects evenly irregular defect shapes bullApplicable to larger defects

COMPARISON WITH OTHER METHODS OF TREATMENTShelliphelliphellip

Abrasion arthroplastyAims to decrease the inflammation of the jointDisadvantagesbullRemoves many cartilage fragments from the jointbullSymptoms reoccur within one year

Drilling and MicrofractureAims to generate a healing responseDisadvantagesbullThe healing response in inadequate bullNo hyaline cartilage is formed but rather fibrocartilage bullHas a limited lifespan of approximately one year bullRapid deterioration after such procedures can be expected

COMPARISON WITH OTHER METHODS OF TREATMENTShelliphelliphellip

Perichondral ResurfacingDisadvantagesbullIsolated cartilage defects are often too large to be covered byh perichondrum bullLong term follow-up of such procedures indicate that the implants undergo endochondral ossification

Synthetic Materials (ie Carbon Fiber Mesh)Disadvantagesbull It often results in fibrous tissue formation bullNot adequate biomechanically bullOften the cause for synovitis in the joints

Osteocartiloginous GraftsAims to reconstruct jointsDisadvantagesbullUnless fresh cartilage is transplanted the cartilage is dead bullFresh grafts are not commonly used as they inevitably carry a risk of disease transmission bullCyropreserved grafts can survive for many years but ultimately deteriorate

Results of the Carticeltrade procedure have been encouraging although it is not always successful An analysis was done of the US and Swedish registry of 153 consecutive patients undergoing this procedure with follow-up from 1 week to 94 months The following results were obtainedbull Patients with clinical improvement 85bull Good or Excellent results 42 bull Good or Excellent results at 2 yearspersisting at 5 years post-op 97

Thus a total of 85 of patients showed some or complete improvement with theimplantation technique The Carticel procedure demonstrated good durability at 5-10 years out

CONCLUSIONS

CONCLUSIONS ACI Vs MACI No current evidence to justify aggressive treatment of

asymptomatic lesions with ACIMACI

Patients with full thickness symptomatic defects do poorly if left untreated

ACI and MACI lead to significant improvement in objective and patient reported clinical outcome scores for up to ten years(even among those with previous failed marrow stimulation techniques)

MACI has a superior rate of clinical improvement in comparison to ACI

Repair tissue may remodel and improve in quality with time

ACI and MACI comparable at 6 years

RECENT ADVANCESHYAFF 3D MATRIX

HYAFF biomaterialscontain high quantities ofderivatized HA

HA-richchondrocyte compatibleembryonic-like mileuconductive to regenerativehealing patterns

bull Non woven felt 2 mm thick fiber diameter 10 micronsbull Chondrocytes are isolated and passaged in culture on plasticdishes up to 3 weeksbull Cells are seeded for 2 weeks on HYAFF scaffold at a density of1 x 106 cm2 resulting in a total of 4 x 106 cm2 seeded cells pergraft

HYAFF-BASED SCAFFOLD

CHONDRONtrade

Uses a cell ndash gel mixture (includes collagen hyaluronic acid and fibrin) that has fast gelling properties (1 ndash 5 min) upon transplantation

This cell and gel mixture enable even cell distribution three-dimensionally moldable to fit irregular defect shape and applicable to a larger defectThus there is minimal surgical exposure and reduced surgery time

(three-dimensional reconstruction of a chondron from the growth plate of the murine long bone the model was generated from multiple sections imaged in an electron microscope plasma membranes are coloured green and internal organelles are visible within the top cell)

RECOVERY TO

HEALTHY ACTIVE LIFE

THANK YOU

• journal club (22-10-09)
• topic autologus chondrocyte implantation
• THE ROLE OF AUTOLOGOUS CHONDROCYTE IMPLANTATION (ACI) IN THE TR
• Slide 4
• AUTOLOGOUS CHONDROCYTE GRAFTS MULTICENTRIC TRIAL WITH 28 KNEE
• Slide 6
• Slide 7
• Articular Cartilage
• Hyaline Cartilage Structure 1048715The ldquostuffrdquo of cartilage
• Slide 11
• Cartilage Injury Occurs in Many Forms
• Articular Cartilage Defects a treatment challenge
• AND WHAT IS IN OUR BASKET
• SO IT LED US TO SEARCH OF MORE PROMISING OPTION
• Autologous Chondrocyte Implantation (ACI) BACKGROUND
• Identifying a Carticelreg Patient
• Identifying a Carticelreg Patienthelliphellip
• Pre-requisite for surgery
• Autologous Chondrocyte Implantation (ACI)
• Techniques
• ACIMACI Generic Method
• Slide 23
• Treatment with CARTICEL
• CARTICEL Manufacturing and Delivery
• Step 2 Implantation
• CARTICEL Implantation
• Periosteal Patch
• Slide 29
• Slide 30
• Aci steps summarised
• Slide 32
• Complications
• Slide 34
• Slide 35
• FOLLOW UP Biopsy
• FOLLOW UP MRI
• FOLLOW UP ARTHROSCOPIC
• Rehabilitation guidelines
• ACI Rehabilitation
• ACI Rehabilitation (2)
• COMPARISON WITH OTHER METHODS OF TREATMENTS
• COMPARISON WITH OTHER METHODS OF TREATMENTShelliphelliphellip
• COMPARISON WITH OTHER METHODS OF TREATMENTShelliphelliphellip (2)
• CONCLUSIONS
• Slide 46
• Recent advancesHYAFF 3D matrix
• HYAFF-based Scaffold
• CHONDRONtrade
• RECOVERY TO
• Slide 51

The overall failure rate is at present quoted as being 10 The two most common complications include bullloosening of the transplant tissue bullformation of fibrous tissue at the repair site and adhesions with return of pain and locking Neither of these complications usually leaves the patient in a worse condition than hisher pre-transplantation state

Other adverse events include bullpost-op haematoma (big blood clot)bullhypertrophic synovitis (angry knee) and superficial wound infection

COMPLICATIONS

IMPROVEMENTS IN CLINICAL OUTCOME

ASSESMENT OF TECHNIQUE

FOLLOW UP RESULTS

ONE YEAR ASSESSMENT

Radiographs Alignment Bone quality

MRI Healing

cartilage Graft failure

Arthroscopy + probe Graft integrity Pressure biopsy

FOLLOW UP BIOPSY

FOLLOW UP MRI

Final appearance of theperiosteum sutured overfemoral condyle defect Thecartilage cells have beeninjected under the flap and thefinal suture placed to close thecover and provide a watertightseal

FOLLOW UP ARTHROSCOPIC

Arthroscopic appearance of thesame area 12 months afterCarticeltrade implantation Thedefect is no longer visible andthere is now hyaline cartilage(biopsy proven) filling theoriginal defect site

REHABILITATION GUIDELINES

Immobilization first 12-24 hours

(CPM) after 12-24 hours for about 4 weeks

Complete joint loading from about 5th week trochleapatellafrom about 8th week condyle Back to sports Low impact rarr within 6 monthsRepeated impact rarr from 8th monthHigh impact rarr from 10-12th month

ACI REHABILITATION

Weight bearingIt is recommended to keep you in non-weight bearing until the second week after surgery (ACI) You can increase the weight bearing gradually and you may be able to sustain your full weight bearing after 6 to 12 weeks from surgery

Range of motionRecovery on your ROM (Range of Motion) is gradually increased with a continuous passive motion (CPM) machine and may be completed to 140 degrees of ROM at 6 weeks to 12 weeks after surgery

ACI REHABILITATIONIndoor exerciseYou can strenghthen your muscles surrounding the knee joint with a four point exercise as well as isometric hamstring and squatting exercises from 4 weeks to 6 weeks after surgeryYou may start performing stationary bike activity without resistance and increase the resistance gradually

Outdoor exerciseAt 13 weeks after surgery you can start walking lightly and at 10 months after surgery you can perform jogging and then you may enjoy intensity exercise like playing tennis or volleyball from 18 months after surgery

Rehabilitation Goals at 12 weeks after ACIFull ROM (Range of Motion) Minimal edema level Minimal occasional pain Pain free tolerance to transitional phase exercise with adequate stability and motor control

COMPARISON WITH OTHER METHODS OF TREATMENTS

Autologous Chondrocyte Implantation Aims to increase the best condition for cartilage defectAdvantagesbullHyaline cartilage is formed bullPermanent reconstructed cartilage tissue bullMost valuable treatment

bullWith Fourth Generation ACI Use of cell ndash gel mixture (collagen hyaluronic acid and fibrin) has fast gelling properties (1 ndash 5 min) upon transplantation bullNo membrane or periosteal patch bullMinimal surgical exposure and reduced surgery time bullCorrects evenly irregular defect shapes bullApplicable to larger defects

COMPARISON WITH OTHER METHODS OF TREATMENTShelliphelliphellip

Abrasion arthroplastyAims to decrease the inflammation of the jointDisadvantagesbullRemoves many cartilage fragments from the jointbullSymptoms reoccur within one year

Drilling and MicrofractureAims to generate a healing responseDisadvantagesbullThe healing response in inadequate bullNo hyaline cartilage is formed but rather fibrocartilage bullHas a limited lifespan of approximately one year bullRapid deterioration after such procedures can be expected

COMPARISON WITH OTHER METHODS OF TREATMENTShelliphelliphellip

Perichondral ResurfacingDisadvantagesbullIsolated cartilage defects are often too large to be covered byh perichondrum bullLong term follow-up of such procedures indicate that the implants undergo endochondral ossification

Synthetic Materials (ie Carbon Fiber Mesh)Disadvantagesbull It often results in fibrous tissue formation bullNot adequate biomechanically bullOften the cause for synovitis in the joints

Osteocartiloginous GraftsAims to reconstruct jointsDisadvantagesbullUnless fresh cartilage is transplanted the cartilage is dead bullFresh grafts are not commonly used as they inevitably carry a risk of disease transmission bullCyropreserved grafts can survive for many years but ultimately deteriorate

Results of the Carticeltrade procedure have been encouraging although it is not always successful An analysis was done of the US and Swedish registry of 153 consecutive patients undergoing this procedure with follow-up from 1 week to 94 months The following results were obtainedbull Patients with clinical improvement 85bull Good or Excellent results 42 bull Good or Excellent results at 2 yearspersisting at 5 years post-op 97

Thus a total of 85 of patients showed some or complete improvement with theimplantation technique The Carticel procedure demonstrated good durability at 5-10 years out

CONCLUSIONS

CONCLUSIONS ACI Vs MACI No current evidence to justify aggressive treatment of

asymptomatic lesions with ACIMACI

Patients with full thickness symptomatic defects do poorly if left untreated

ACI and MACI lead to significant improvement in objective and patient reported clinical outcome scores for up to ten years(even among those with previous failed marrow stimulation techniques)

MACI has a superior rate of clinical improvement in comparison to ACI

Repair tissue may remodel and improve in quality with time

ACI and MACI comparable at 6 years

RECENT ADVANCESHYAFF 3D MATRIX

HYAFF biomaterialscontain high quantities ofderivatized HA

HA-richchondrocyte compatibleembryonic-like mileuconductive to regenerativehealing patterns

bull Non woven felt 2 mm thick fiber diameter 10 micronsbull Chondrocytes are isolated and passaged in culture on plasticdishes up to 3 weeksbull Cells are seeded for 2 weeks on HYAFF scaffold at a density of1 x 106 cm2 resulting in a total of 4 x 106 cm2 seeded cells pergraft

HYAFF-BASED SCAFFOLD

CHONDRONtrade

Uses a cell ndash gel mixture (includes collagen hyaluronic acid and fibrin) that has fast gelling properties (1 ndash 5 min) upon transplantation

This cell and gel mixture enable even cell distribution three-dimensionally moldable to fit irregular defect shape and applicable to a larger defectThus there is minimal surgical exposure and reduced surgery time

(three-dimensional reconstruction of a chondron from the growth plate of the murine long bone the model was generated from multiple sections imaged in an electron microscope plasma membranes are coloured green and internal organelles are visible within the top cell)

RECOVERY TO

HEALTHY ACTIVE LIFE

THANK YOU

• journal club (22-10-09)
• topic autologus chondrocyte implantation
• THE ROLE OF AUTOLOGOUS CHONDROCYTE IMPLANTATION (ACI) IN THE TR
• Slide 4
• AUTOLOGOUS CHONDROCYTE GRAFTS MULTICENTRIC TRIAL WITH 28 KNEE
• Slide 6
• Slide 7
• Articular Cartilage
• Hyaline Cartilage Structure 1048715The ldquostuffrdquo of cartilage
• Slide 11
• Cartilage Injury Occurs in Many Forms
• Articular Cartilage Defects a treatment challenge
• AND WHAT IS IN OUR BASKET
• SO IT LED US TO SEARCH OF MORE PROMISING OPTION
• Autologous Chondrocyte Implantation (ACI) BACKGROUND
• Identifying a Carticelreg Patient
• Identifying a Carticelreg Patienthelliphellip
• Pre-requisite for surgery
• Autologous Chondrocyte Implantation (ACI)
• Techniques
• ACIMACI Generic Method
• Slide 23
• Treatment with CARTICEL
• CARTICEL Manufacturing and Delivery
• Step 2 Implantation
• CARTICEL Implantation
• Periosteal Patch
• Slide 29
• Slide 30
• Aci steps summarised
• Slide 32
• Complications
• Slide 34
• Slide 35
• FOLLOW UP Biopsy
• FOLLOW UP MRI
• FOLLOW UP ARTHROSCOPIC
• Rehabilitation guidelines
• ACI Rehabilitation
• ACI Rehabilitation (2)
• COMPARISON WITH OTHER METHODS OF TREATMENTS
• COMPARISON WITH OTHER METHODS OF TREATMENTShelliphelliphellip
• COMPARISON WITH OTHER METHODS OF TREATMENTShelliphelliphellip (2)
• CONCLUSIONS
• Slide 46
• Recent advancesHYAFF 3D matrix
• HYAFF-based Scaffold
• CHONDRONtrade
• RECOVERY TO
• Slide 51

IMPROVEMENTS IN CLINICAL OUTCOME

ASSESMENT OF TECHNIQUE

FOLLOW UP RESULTS

ONE YEAR ASSESSMENT

Radiographs Alignment Bone quality

MRI Healing

cartilage Graft failure

Arthroscopy + probe Graft integrity Pressure biopsy

FOLLOW UP BIOPSY

FOLLOW UP MRI

Final appearance of theperiosteum sutured overfemoral condyle defect Thecartilage cells have beeninjected under the flap and thefinal suture placed to close thecover and provide a watertightseal

FOLLOW UP ARTHROSCOPIC

Arthroscopic appearance of thesame area 12 months afterCarticeltrade implantation Thedefect is no longer visible andthere is now hyaline cartilage(biopsy proven) filling theoriginal defect site

REHABILITATION GUIDELINES

Immobilization first 12-24 hours

(CPM) after 12-24 hours for about 4 weeks

Complete joint loading from about 5th week trochleapatellafrom about 8th week condyle Back to sports Low impact rarr within 6 monthsRepeated impact rarr from 8th monthHigh impact rarr from 10-12th month

ACI REHABILITATION

Weight bearingIt is recommended to keep you in non-weight bearing until the second week after surgery (ACI) You can increase the weight bearing gradually and you may be able to sustain your full weight bearing after 6 to 12 weeks from surgery

Range of motionRecovery on your ROM (Range of Motion) is gradually increased with a continuous passive motion (CPM) machine and may be completed to 140 degrees of ROM at 6 weeks to 12 weeks after surgery

ACI REHABILITATIONIndoor exerciseYou can strenghthen your muscles surrounding the knee joint with a four point exercise as well as isometric hamstring and squatting exercises from 4 weeks to 6 weeks after surgeryYou may start performing stationary bike activity without resistance and increase the resistance gradually

Outdoor exerciseAt 13 weeks after surgery you can start walking lightly and at 10 months after surgery you can perform jogging and then you may enjoy intensity exercise like playing tennis or volleyball from 18 months after surgery

Rehabilitation Goals at 12 weeks after ACIFull ROM (Range of Motion) Minimal edema level Minimal occasional pain Pain free tolerance to transitional phase exercise with adequate stability and motor control

COMPARISON WITH OTHER METHODS OF TREATMENTS

Autologous Chondrocyte Implantation Aims to increase the best condition for cartilage defectAdvantagesbullHyaline cartilage is formed bullPermanent reconstructed cartilage tissue bullMost valuable treatment

bullWith Fourth Generation ACI Use of cell ndash gel mixture (collagen hyaluronic acid and fibrin) has fast gelling properties (1 ndash 5 min) upon transplantation bullNo membrane or periosteal patch bullMinimal surgical exposure and reduced surgery time bullCorrects evenly irregular defect shapes bullApplicable to larger defects

COMPARISON WITH OTHER METHODS OF TREATMENTShelliphelliphellip

Abrasion arthroplastyAims to decrease the inflammation of the jointDisadvantagesbullRemoves many cartilage fragments from the jointbullSymptoms reoccur within one year

Drilling and MicrofractureAims to generate a healing responseDisadvantagesbullThe healing response in inadequate bullNo hyaline cartilage is formed but rather fibrocartilage bullHas a limited lifespan of approximately one year bullRapid deterioration after such procedures can be expected

COMPARISON WITH OTHER METHODS OF TREATMENTShelliphelliphellip

Perichondral ResurfacingDisadvantagesbullIsolated cartilage defects are often too large to be covered byh perichondrum bullLong term follow-up of such procedures indicate that the implants undergo endochondral ossification

Synthetic Materials (ie Carbon Fiber Mesh)Disadvantagesbull It often results in fibrous tissue formation bullNot adequate biomechanically bullOften the cause for synovitis in the joints

Osteocartiloginous GraftsAims to reconstruct jointsDisadvantagesbullUnless fresh cartilage is transplanted the cartilage is dead bullFresh grafts are not commonly used as they inevitably carry a risk of disease transmission bullCyropreserved grafts can survive for many years but ultimately deteriorate

Results of the Carticeltrade procedure have been encouraging although it is not always successful An analysis was done of the US and Swedish registry of 153 consecutive patients undergoing this procedure with follow-up from 1 week to 94 months The following results were obtainedbull Patients with clinical improvement 85bull Good or Excellent results 42 bull Good or Excellent results at 2 yearspersisting at 5 years post-op 97

Thus a total of 85 of patients showed some or complete improvement with theimplantation technique The Carticel procedure demonstrated good durability at 5-10 years out

CONCLUSIONS

CONCLUSIONS ACI Vs MACI No current evidence to justify aggressive treatment of

asymptomatic lesions with ACIMACI

Patients with full thickness symptomatic defects do poorly if left untreated

ACI and MACI lead to significant improvement in objective and patient reported clinical outcome scores for up to ten years(even among those with previous failed marrow stimulation techniques)

MACI has a superior rate of clinical improvement in comparison to ACI

Repair tissue may remodel and improve in quality with time

ACI and MACI comparable at 6 years

RECENT ADVANCESHYAFF 3D MATRIX

HYAFF biomaterialscontain high quantities ofderivatized HA

HA-richchondrocyte compatibleembryonic-like mileuconductive to regenerativehealing patterns

bull Non woven felt 2 mm thick fiber diameter 10 micronsbull Chondrocytes are isolated and passaged in culture on plasticdishes up to 3 weeksbull Cells are seeded for 2 weeks on HYAFF scaffold at a density of1 x 106 cm2 resulting in a total of 4 x 106 cm2 seeded cells pergraft

HYAFF-BASED SCAFFOLD

CHONDRONtrade

Uses a cell ndash gel mixture (includes collagen hyaluronic acid and fibrin) that has fast gelling properties (1 ndash 5 min) upon transplantation

This cell and gel mixture enable even cell distribution three-dimensionally moldable to fit irregular defect shape and applicable to a larger defectThus there is minimal surgical exposure and reduced surgery time

(three-dimensional reconstruction of a chondron from the growth plate of the murine long bone the model was generated from multiple sections imaged in an electron microscope plasma membranes are coloured green and internal organelles are visible within the top cell)

RECOVERY TO

HEALTHY ACTIVE LIFE

THANK YOU

• journal club (22-10-09)
• topic autologus chondrocyte implantation
• THE ROLE OF AUTOLOGOUS CHONDROCYTE IMPLANTATION (ACI) IN THE TR
• Slide 4
• AUTOLOGOUS CHONDROCYTE GRAFTS MULTICENTRIC TRIAL WITH 28 KNEE
• Slide 6
• Slide 7
• Articular Cartilage
• Hyaline Cartilage Structure 1048715The ldquostuffrdquo of cartilage
• Slide 11
• Cartilage Injury Occurs in Many Forms
• Articular Cartilage Defects a treatment challenge
• AND WHAT IS IN OUR BASKET
• SO IT LED US TO SEARCH OF MORE PROMISING OPTION
• Autologous Chondrocyte Implantation (ACI) BACKGROUND
• Identifying a Carticelreg Patient
• Identifying a Carticelreg Patienthelliphellip
• Pre-requisite for surgery
• Autologous Chondrocyte Implantation (ACI)
• Techniques
• ACIMACI Generic Method
• Slide 23
• Treatment with CARTICEL
• CARTICEL Manufacturing and Delivery
• Step 2 Implantation
• CARTICEL Implantation
• Periosteal Patch
• Slide 29
• Slide 30
• Aci steps summarised
• Slide 32
• Complications
• Slide 34
• Slide 35
• FOLLOW UP Biopsy
• FOLLOW UP MRI
• FOLLOW UP ARTHROSCOPIC
• Rehabilitation guidelines
• ACI Rehabilitation
• ACI Rehabilitation (2)
• COMPARISON WITH OTHER METHODS OF TREATMENTS
• COMPARISON WITH OTHER METHODS OF TREATMENTShelliphelliphellip
• COMPARISON WITH OTHER METHODS OF TREATMENTShelliphelliphellip (2)
• CONCLUSIONS
• Slide 46
• Recent advancesHYAFF 3D matrix
• HYAFF-based Scaffold
• CHONDRONtrade
• RECOVERY TO
• Slide 51

ONE YEAR ASSESSMENT

Radiographs Alignment Bone quality

MRI Healing

cartilage Graft failure

Arthroscopy + probe Graft integrity Pressure biopsy

FOLLOW UP BIOPSY

FOLLOW UP MRI

Final appearance of theperiosteum sutured overfemoral condyle defect Thecartilage cells have beeninjected under the flap and thefinal suture placed to close thecover and provide a watertightseal

FOLLOW UP ARTHROSCOPIC

Arthroscopic appearance of thesame area 12 months afterCarticeltrade implantation Thedefect is no longer visible andthere is now hyaline cartilage(biopsy proven) filling theoriginal defect site

REHABILITATION GUIDELINES

Immobilization first 12-24 hours

(CPM) after 12-24 hours for about 4 weeks

Complete joint loading from about 5th week trochleapatellafrom about 8th week condyle Back to sports Low impact rarr within 6 monthsRepeated impact rarr from 8th monthHigh impact rarr from 10-12th month

ACI REHABILITATION

Weight bearingIt is recommended to keep you in non-weight bearing until the second week after surgery (ACI) You can increase the weight bearing gradually and you may be able to sustain your full weight bearing after 6 to 12 weeks from surgery

Range of motionRecovery on your ROM (Range of Motion) is gradually increased with a continuous passive motion (CPM) machine and may be completed to 140 degrees of ROM at 6 weeks to 12 weeks after surgery

ACI REHABILITATIONIndoor exerciseYou can strenghthen your muscles surrounding the knee joint with a four point exercise as well as isometric hamstring and squatting exercises from 4 weeks to 6 weeks after surgeryYou may start performing stationary bike activity without resistance and increase the resistance gradually

Outdoor exerciseAt 13 weeks after surgery you can start walking lightly and at 10 months after surgery you can perform jogging and then you may enjoy intensity exercise like playing tennis or volleyball from 18 months after surgery

Rehabilitation Goals at 12 weeks after ACIFull ROM (Range of Motion) Minimal edema level Minimal occasional pain Pain free tolerance to transitional phase exercise with adequate stability and motor control

COMPARISON WITH OTHER METHODS OF TREATMENTS

Autologous Chondrocyte Implantation Aims to increase the best condition for cartilage defectAdvantagesbullHyaline cartilage is formed bullPermanent reconstructed cartilage tissue bullMost valuable treatment

bullWith Fourth Generation ACI Use of cell ndash gel mixture (collagen hyaluronic acid and fibrin) has fast gelling properties (1 ndash 5 min) upon transplantation bullNo membrane or periosteal patch bullMinimal surgical exposure and reduced surgery time bullCorrects evenly irregular defect shapes bullApplicable to larger defects

COMPARISON WITH OTHER METHODS OF TREATMENTShelliphelliphellip

Abrasion arthroplastyAims to decrease the inflammation of the jointDisadvantagesbullRemoves many cartilage fragments from the jointbullSymptoms reoccur within one year

Drilling and MicrofractureAims to generate a healing responseDisadvantagesbullThe healing response in inadequate bullNo hyaline cartilage is formed but rather fibrocartilage bullHas a limited lifespan of approximately one year bullRapid deterioration after such procedures can be expected

COMPARISON WITH OTHER METHODS OF TREATMENTShelliphelliphellip

Perichondral ResurfacingDisadvantagesbullIsolated cartilage defects are often too large to be covered byh perichondrum bullLong term follow-up of such procedures indicate that the implants undergo endochondral ossification

Synthetic Materials (ie Carbon Fiber Mesh)Disadvantagesbull It often results in fibrous tissue formation bullNot adequate biomechanically bullOften the cause for synovitis in the joints

Osteocartiloginous GraftsAims to reconstruct jointsDisadvantagesbullUnless fresh cartilage is transplanted the cartilage is dead bullFresh grafts are not commonly used as they inevitably carry a risk of disease transmission bullCyropreserved grafts can survive for many years but ultimately deteriorate

Results of the Carticeltrade procedure have been encouraging although it is not always successful An analysis was done of the US and Swedish registry of 153 consecutive patients undergoing this procedure with follow-up from 1 week to 94 months The following results were obtainedbull Patients with clinical improvement 85bull Good or Excellent results 42 bull Good or Excellent results at 2 yearspersisting at 5 years post-op 97

Thus a total of 85 of patients showed some or complete improvement with theimplantation technique The Carticel procedure demonstrated good durability at 5-10 years out

CONCLUSIONS

CONCLUSIONS ACI Vs MACI No current evidence to justify aggressive treatment of

asymptomatic lesions with ACIMACI

Patients with full thickness symptomatic defects do poorly if left untreated

ACI and MACI lead to significant improvement in objective and patient reported clinical outcome scores for up to ten years(even among those with previous failed marrow stimulation techniques)

MACI has a superior rate of clinical improvement in comparison to ACI

Repair tissue may remodel and improve in quality with time

ACI and MACI comparable at 6 years

RECENT ADVANCESHYAFF 3D MATRIX

HYAFF biomaterialscontain high quantities ofderivatized HA

HA-richchondrocyte compatibleembryonic-like mileuconductive to regenerativehealing patterns

bull Non woven felt 2 mm thick fiber diameter 10 micronsbull Chondrocytes are isolated and passaged in culture on plasticdishes up to 3 weeksbull Cells are seeded for 2 weeks on HYAFF scaffold at a density of1 x 106 cm2 resulting in a total of 4 x 106 cm2 seeded cells pergraft

HYAFF-BASED SCAFFOLD

CHONDRONtrade

Uses a cell ndash gel mixture (includes collagen hyaluronic acid and fibrin) that has fast gelling properties (1 ndash 5 min) upon transplantation

This cell and gel mixture enable even cell distribution three-dimensionally moldable to fit irregular defect shape and applicable to a larger defectThus there is minimal surgical exposure and reduced surgery time

(three-dimensional reconstruction of a chondron from the growth plate of the murine long bone the model was generated from multiple sections imaged in an electron microscope plasma membranes are coloured green and internal organelles are visible within the top cell)

RECOVERY TO

HEALTHY ACTIVE LIFE

THANK YOU

• journal club (22-10-09)
• topic autologus chondrocyte implantation
• THE ROLE OF AUTOLOGOUS CHONDROCYTE IMPLANTATION (ACI) IN THE TR
• Slide 4
• AUTOLOGOUS CHONDROCYTE GRAFTS MULTICENTRIC TRIAL WITH 28 KNEE
• Slide 6
• Slide 7
• Articular Cartilage
• Hyaline Cartilage Structure 1048715The ldquostuffrdquo of cartilage
• Slide 11
• Cartilage Injury Occurs in Many Forms
• Articular Cartilage Defects a treatment challenge
• AND WHAT IS IN OUR BASKET
• SO IT LED US TO SEARCH OF MORE PROMISING OPTION
• Autologous Chondrocyte Implantation (ACI) BACKGROUND
• Identifying a Carticelreg Patient
• Identifying a Carticelreg Patienthelliphellip
• Pre-requisite for surgery
• Autologous Chondrocyte Implantation (ACI)
• Techniques
• ACIMACI Generic Method
• Slide 23
• Treatment with CARTICEL
• CARTICEL Manufacturing and Delivery
• Step 2 Implantation
• CARTICEL Implantation
• Periosteal Patch
• Slide 29
• Slide 30
• Aci steps summarised
• Slide 32
• Complications
• Slide 34
• Slide 35
• FOLLOW UP Biopsy
• FOLLOW UP MRI
• FOLLOW UP ARTHROSCOPIC
• Rehabilitation guidelines
• ACI Rehabilitation
• ACI Rehabilitation (2)
• COMPARISON WITH OTHER METHODS OF TREATMENTS
• COMPARISON WITH OTHER METHODS OF TREATMENTShelliphelliphellip
• COMPARISON WITH OTHER METHODS OF TREATMENTShelliphelliphellip (2)
• CONCLUSIONS
• Slide 46
• Recent advancesHYAFF 3D matrix
• HYAFF-based Scaffold
• CHONDRONtrade
• RECOVERY TO
• Slide 51

FOLLOW UP BIOPSY

FOLLOW UP MRI

Final appearance of theperiosteum sutured overfemoral condyle defect Thecartilage cells have beeninjected under the flap and thefinal suture placed to close thecover and provide a watertightseal

FOLLOW UP ARTHROSCOPIC

Arthroscopic appearance of thesame area 12 months afterCarticeltrade implantation Thedefect is no longer visible andthere is now hyaline cartilage(biopsy proven) filling theoriginal defect site

REHABILITATION GUIDELINES

Immobilization first 12-24 hours

(CPM) after 12-24 hours for about 4 weeks

Complete joint loading from about 5th week trochleapatellafrom about 8th week condyle Back to sports Low impact rarr within 6 monthsRepeated impact rarr from 8th monthHigh impact rarr from 10-12th month

ACI REHABILITATION

Weight bearingIt is recommended to keep you in non-weight bearing until the second week after surgery (ACI) You can increase the weight bearing gradually and you may be able to sustain your full weight bearing after 6 to 12 weeks from surgery

Range of motionRecovery on your ROM (Range of Motion) is gradually increased with a continuous passive motion (CPM) machine and may be completed to 140 degrees of ROM at 6 weeks to 12 weeks after surgery

ACI REHABILITATIONIndoor exerciseYou can strenghthen your muscles surrounding the knee joint with a four point exercise as well as isometric hamstring and squatting exercises from 4 weeks to 6 weeks after surgeryYou may start performing stationary bike activity without resistance and increase the resistance gradually

Outdoor exerciseAt 13 weeks after surgery you can start walking lightly and at 10 months after surgery you can perform jogging and then you may enjoy intensity exercise like playing tennis or volleyball from 18 months after surgery

Rehabilitation Goals at 12 weeks after ACIFull ROM (Range of Motion) Minimal edema level Minimal occasional pain Pain free tolerance to transitional phase exercise with adequate stability and motor control

COMPARISON WITH OTHER METHODS OF TREATMENTS

Autologous Chondrocyte Implantation Aims to increase the best condition for cartilage defectAdvantagesbullHyaline cartilage is formed bullPermanent reconstructed cartilage tissue bullMost valuable treatment

bullWith Fourth Generation ACI Use of cell ndash gel mixture (collagen hyaluronic acid and fibrin) has fast gelling properties (1 ndash 5 min) upon transplantation bullNo membrane or periosteal patch bullMinimal surgical exposure and reduced surgery time bullCorrects evenly irregular defect shapes bullApplicable to larger defects

COMPARISON WITH OTHER METHODS OF TREATMENTShelliphelliphellip

Abrasion arthroplastyAims to decrease the inflammation of the jointDisadvantagesbullRemoves many cartilage fragments from the jointbullSymptoms reoccur within one year

Drilling and MicrofractureAims to generate a healing responseDisadvantagesbullThe healing response in inadequate bullNo hyaline cartilage is formed but rather fibrocartilage bullHas a limited lifespan of approximately one year bullRapid deterioration after such procedures can be expected

COMPARISON WITH OTHER METHODS OF TREATMENTShelliphelliphellip

Perichondral ResurfacingDisadvantagesbullIsolated cartilage defects are often too large to be covered byh perichondrum bullLong term follow-up of such procedures indicate that the implants undergo endochondral ossification

Synthetic Materials (ie Carbon Fiber Mesh)Disadvantagesbull It often results in fibrous tissue formation bullNot adequate biomechanically bullOften the cause for synovitis in the joints

Osteocartiloginous GraftsAims to reconstruct jointsDisadvantagesbullUnless fresh cartilage is transplanted the cartilage is dead bullFresh grafts are not commonly used as they inevitably carry a risk of disease transmission bullCyropreserved grafts can survive for many years but ultimately deteriorate

Results of the Carticeltrade procedure have been encouraging although it is not always successful An analysis was done of the US and Swedish registry of 153 consecutive patients undergoing this procedure with follow-up from 1 week to 94 months The following results were obtainedbull Patients with clinical improvement 85bull Good or Excellent results 42 bull Good or Excellent results at 2 yearspersisting at 5 years post-op 97

Thus a total of 85 of patients showed some or complete improvement with theimplantation technique The Carticel procedure demonstrated good durability at 5-10 years out

CONCLUSIONS

CONCLUSIONS ACI Vs MACI No current evidence to justify aggressive treatment of

asymptomatic lesions with ACIMACI

Patients with full thickness symptomatic defects do poorly if left untreated

ACI and MACI lead to significant improvement in objective and patient reported clinical outcome scores for up to ten years(even among those with previous failed marrow stimulation techniques)

MACI has a superior rate of clinical improvement in comparison to ACI

Repair tissue may remodel and improve in quality with time

ACI and MACI comparable at 6 years

RECENT ADVANCESHYAFF 3D MATRIX

HYAFF biomaterialscontain high quantities ofderivatized HA

HA-richchondrocyte compatibleembryonic-like mileuconductive to regenerativehealing patterns

bull Non woven felt 2 mm thick fiber diameter 10 micronsbull Chondrocytes are isolated and passaged in culture on plasticdishes up to 3 weeksbull Cells are seeded for 2 weeks on HYAFF scaffold at a density of1 x 106 cm2 resulting in a total of 4 x 106 cm2 seeded cells pergraft

HYAFF-BASED SCAFFOLD

CHONDRONtrade

Uses a cell ndash gel mixture (includes collagen hyaluronic acid and fibrin) that has fast gelling properties (1 ndash 5 min) upon transplantation

This cell and gel mixture enable even cell distribution three-dimensionally moldable to fit irregular defect shape and applicable to a larger defectThus there is minimal surgical exposure and reduced surgery time

(three-dimensional reconstruction of a chondron from the growth plate of the murine long bone the model was generated from multiple sections imaged in an electron microscope plasma membranes are coloured green and internal organelles are visible within the top cell)

RECOVERY TO

HEALTHY ACTIVE LIFE

THANK YOU

• journal club (22-10-09)
• topic autologus chondrocyte implantation
• THE ROLE OF AUTOLOGOUS CHONDROCYTE IMPLANTATION (ACI) IN THE TR
• Slide 4
• AUTOLOGOUS CHONDROCYTE GRAFTS MULTICENTRIC TRIAL WITH 28 KNEE
• Slide 6
• Slide 7
• Articular Cartilage
• Hyaline Cartilage Structure 1048715The ldquostuffrdquo of cartilage
• Slide 11
• Cartilage Injury Occurs in Many Forms
• Articular Cartilage Defects a treatment challenge
• AND WHAT IS IN OUR BASKET
• SO IT LED US TO SEARCH OF MORE PROMISING OPTION
• Autologous Chondrocyte Implantation (ACI) BACKGROUND
• Identifying a Carticelreg Patient
• Identifying a Carticelreg Patienthelliphellip
• Pre-requisite for surgery
• Autologous Chondrocyte Implantation (ACI)
• Techniques
• ACIMACI Generic Method
• Slide 23
• Treatment with CARTICEL
• CARTICEL Manufacturing and Delivery
• Step 2 Implantation
• CARTICEL Implantation
• Periosteal Patch
• Slide 29
• Slide 30
• Aci steps summarised
• Slide 32
• Complications
• Slide 34
• Slide 35
• FOLLOW UP Biopsy
• FOLLOW UP MRI
• FOLLOW UP ARTHROSCOPIC
• Rehabilitation guidelines
• ACI Rehabilitation
• ACI Rehabilitation (2)
• COMPARISON WITH OTHER METHODS OF TREATMENTS
• COMPARISON WITH OTHER METHODS OF TREATMENTShelliphelliphellip
• COMPARISON WITH OTHER METHODS OF TREATMENTShelliphelliphellip (2)
• CONCLUSIONS
• Slide 46
• Recent advancesHYAFF 3D matrix
• HYAFF-based Scaffold
• CHONDRONtrade
• RECOVERY TO
• Slide 51

FOLLOW UP MRI

Final appearance of theperiosteum sutured overfemoral condyle defect Thecartilage cells have beeninjected under the flap and thefinal suture placed to close thecover and provide a watertightseal

FOLLOW UP ARTHROSCOPIC

Arthroscopic appearance of thesame area 12 months afterCarticeltrade implantation Thedefect is no longer visible andthere is now hyaline cartilage(biopsy proven) filling theoriginal defect site

REHABILITATION GUIDELINES

Immobilization first 12-24 hours

(CPM) after 12-24 hours for about 4 weeks

Complete joint loading from about 5th week trochleapatellafrom about 8th week condyle Back to sports Low impact rarr within 6 monthsRepeated impact rarr from 8th monthHigh impact rarr from 10-12th month

ACI REHABILITATION

Weight bearingIt is recommended to keep you in non-weight bearing until the second week after surgery (ACI) You can increase the weight bearing gradually and you may be able to sustain your full weight bearing after 6 to 12 weeks from surgery

Range of motionRecovery on your ROM (Range of Motion) is gradually increased with a continuous passive motion (CPM) machine and may be completed to 140 degrees of ROM at 6 weeks to 12 weeks after surgery

ACI REHABILITATIONIndoor exerciseYou can strenghthen your muscles surrounding the knee joint with a four point exercise as well as isometric hamstring and squatting exercises from 4 weeks to 6 weeks after surgeryYou may start performing stationary bike activity without resistance and increase the resistance gradually

Outdoor exerciseAt 13 weeks after surgery you can start walking lightly and at 10 months after surgery you can perform jogging and then you may enjoy intensity exercise like playing tennis or volleyball from 18 months after surgery

Rehabilitation Goals at 12 weeks after ACIFull ROM (Range of Motion) Minimal edema level Minimal occasional pain Pain free tolerance to transitional phase exercise with adequate stability and motor control

COMPARISON WITH OTHER METHODS OF TREATMENTS

Autologous Chondrocyte Implantation Aims to increase the best condition for cartilage defectAdvantagesbullHyaline cartilage is formed bullPermanent reconstructed cartilage tissue bullMost valuable treatment

bullWith Fourth Generation ACI Use of cell ndash gel mixture (collagen hyaluronic acid and fibrin) has fast gelling properties (1 ndash 5 min) upon transplantation bullNo membrane or periosteal patch bullMinimal surgical exposure and reduced surgery time bullCorrects evenly irregular defect shapes bullApplicable to larger defects

COMPARISON WITH OTHER METHODS OF TREATMENTShelliphelliphellip

Abrasion arthroplastyAims to decrease the inflammation of the jointDisadvantagesbullRemoves many cartilage fragments from the jointbullSymptoms reoccur within one year

Drilling and MicrofractureAims to generate a healing responseDisadvantagesbullThe healing response in inadequate bullNo hyaline cartilage is formed but rather fibrocartilage bullHas a limited lifespan of approximately one year bullRapid deterioration after such procedures can be expected

COMPARISON WITH OTHER METHODS OF TREATMENTShelliphelliphellip

Perichondral ResurfacingDisadvantagesbullIsolated cartilage defects are often too large to be covered byh perichondrum bullLong term follow-up of such procedures indicate that the implants undergo endochondral ossification

Synthetic Materials (ie Carbon Fiber Mesh)Disadvantagesbull It often results in fibrous tissue formation bullNot adequate biomechanically bullOften the cause for synovitis in the joints

Osteocartiloginous GraftsAims to reconstruct jointsDisadvantagesbullUnless fresh cartilage is transplanted the cartilage is dead bullFresh grafts are not commonly used as they inevitably carry a risk of disease transmission bullCyropreserved grafts can survive for many years but ultimately deteriorate

Results of the Carticeltrade procedure have been encouraging although it is not always successful An analysis was done of the US and Swedish registry of 153 consecutive patients undergoing this procedure with follow-up from 1 week to 94 months The following results were obtainedbull Patients with clinical improvement 85bull Good or Excellent results 42 bull Good or Excellent results at 2 yearspersisting at 5 years post-op 97

Thus a total of 85 of patients showed some or complete improvement with theimplantation technique The Carticel procedure demonstrated good durability at 5-10 years out

CONCLUSIONS

CONCLUSIONS ACI Vs MACI No current evidence to justify aggressive treatment of

asymptomatic lesions with ACIMACI

Patients with full thickness symptomatic defects do poorly if left untreated

ACI and MACI lead to significant improvement in objective and patient reported clinical outcome scores for up to ten years(even among those with previous failed marrow stimulation techniques)

MACI has a superior rate of clinical improvement in comparison to ACI

Repair tissue may remodel and improve in quality with time

ACI and MACI comparable at 6 years

RECENT ADVANCESHYAFF 3D MATRIX

HYAFF biomaterialscontain high quantities ofderivatized HA

HA-richchondrocyte compatibleembryonic-like mileuconductive to regenerativehealing patterns

bull Non woven felt 2 mm thick fiber diameter 10 micronsbull Chondrocytes are isolated and passaged in culture on plasticdishes up to 3 weeksbull Cells are seeded for 2 weeks on HYAFF scaffold at a density of1 x 106 cm2 resulting in a total of 4 x 106 cm2 seeded cells pergraft

HYAFF-BASED SCAFFOLD

CHONDRONtrade

Uses a cell ndash gel mixture (includes collagen hyaluronic acid and fibrin) that has fast gelling properties (1 ndash 5 min) upon transplantation

This cell and gel mixture enable even cell distribution three-dimensionally moldable to fit irregular defect shape and applicable to a larger defectThus there is minimal surgical exposure and reduced surgery time

(three-dimensional reconstruction of a chondron from the growth plate of the murine long bone the model was generated from multiple sections imaged in an electron microscope plasma membranes are coloured green and internal organelles are visible within the top cell)

RECOVERY TO

HEALTHY ACTIVE LIFE

THANK YOU

• journal club (22-10-09)
• topic autologus chondrocyte implantation
• THE ROLE OF AUTOLOGOUS CHONDROCYTE IMPLANTATION (ACI) IN THE TR
• Slide 4
• AUTOLOGOUS CHONDROCYTE GRAFTS MULTICENTRIC TRIAL WITH 28 KNEE
• Slide 6
• Slide 7
• Articular Cartilage
• Hyaline Cartilage Structure 1048715The ldquostuffrdquo of cartilage
• Slide 11
• Cartilage Injury Occurs in Many Forms
• Articular Cartilage Defects a treatment challenge
• AND WHAT IS IN OUR BASKET
• SO IT LED US TO SEARCH OF MORE PROMISING OPTION
• Autologous Chondrocyte Implantation (ACI) BACKGROUND
• Identifying a Carticelreg Patient
• Identifying a Carticelreg Patienthelliphellip
• Pre-requisite for surgery
• Autologous Chondrocyte Implantation (ACI)
• Techniques
• ACIMACI Generic Method
• Slide 23
• Treatment with CARTICEL
• CARTICEL Manufacturing and Delivery
• Step 2 Implantation
• CARTICEL Implantation
• Periosteal Patch
• Slide 29
• Slide 30
• Aci steps summarised
• Slide 32
• Complications
• Slide 34
• Slide 35
• FOLLOW UP Biopsy
• FOLLOW UP MRI
• FOLLOW UP ARTHROSCOPIC
• Rehabilitation guidelines
• ACI Rehabilitation
• ACI Rehabilitation (2)
• COMPARISON WITH OTHER METHODS OF TREATMENTS
• COMPARISON WITH OTHER METHODS OF TREATMENTShelliphelliphellip
• COMPARISON WITH OTHER METHODS OF TREATMENTShelliphelliphellip (2)
• CONCLUSIONS
• Slide 46
• Recent advancesHYAFF 3D matrix
• HYAFF-based Scaffold
• CHONDRONtrade
• RECOVERY TO
• Slide 51

Final appearance of theperiosteum sutured overfemoral condyle defect Thecartilage cells have beeninjected under the flap and thefinal suture placed to close thecover and provide a watertightseal

FOLLOW UP ARTHROSCOPIC

Arthroscopic appearance of thesame area 12 months afterCarticeltrade implantation Thedefect is no longer visible andthere is now hyaline cartilage(biopsy proven) filling theoriginal defect site

REHABILITATION GUIDELINES

Immobilization first 12-24 hours

(CPM) after 12-24 hours for about 4 weeks

Complete joint loading from about 5th week trochleapatellafrom about 8th week condyle Back to sports Low impact rarr within 6 monthsRepeated impact rarr from 8th monthHigh impact rarr from 10-12th month

ACI REHABILITATION

Weight bearingIt is recommended to keep you in non-weight bearing until the second week after surgery (ACI) You can increase the weight bearing gradually and you may be able to sustain your full weight bearing after 6 to 12 weeks from surgery

Range of motionRecovery on your ROM (Range of Motion) is gradually increased with a continuous passive motion (CPM) machine and may be completed to 140 degrees of ROM at 6 weeks to 12 weeks after surgery

ACI REHABILITATIONIndoor exerciseYou can strenghthen your muscles surrounding the knee joint with a four point exercise as well as isometric hamstring and squatting exercises from 4 weeks to 6 weeks after surgeryYou may start performing stationary bike activity without resistance and increase the resistance gradually

Outdoor exerciseAt 13 weeks after surgery you can start walking lightly and at 10 months after surgery you can perform jogging and then you may enjoy intensity exercise like playing tennis or volleyball from 18 months after surgery

Rehabilitation Goals at 12 weeks after ACIFull ROM (Range of Motion) Minimal edema level Minimal occasional pain Pain free tolerance to transitional phase exercise with adequate stability and motor control

COMPARISON WITH OTHER METHODS OF TREATMENTS

Autologous Chondrocyte Implantation Aims to increase the best condition for cartilage defectAdvantagesbullHyaline cartilage is formed bullPermanent reconstructed cartilage tissue bullMost valuable treatment

bullWith Fourth Generation ACI Use of cell ndash gel mixture (collagen hyaluronic acid and fibrin) has fast gelling properties (1 ndash 5 min) upon transplantation bullNo membrane or periosteal patch bullMinimal surgical exposure and reduced surgery time bullCorrects evenly irregular defect shapes bullApplicable to larger defects

COMPARISON WITH OTHER METHODS OF TREATMENTShelliphelliphellip

Abrasion arthroplastyAims to decrease the inflammation of the jointDisadvantagesbullRemoves many cartilage fragments from the jointbullSymptoms reoccur within one year

Drilling and MicrofractureAims to generate a healing responseDisadvantagesbullThe healing response in inadequate bullNo hyaline cartilage is formed but rather fibrocartilage bullHas a limited lifespan of approximately one year bullRapid deterioration after such procedures can be expected

COMPARISON WITH OTHER METHODS OF TREATMENTShelliphelliphellip

Perichondral ResurfacingDisadvantagesbullIsolated cartilage defects are often too large to be covered byh perichondrum bullLong term follow-up of such procedures indicate that the implants undergo endochondral ossification

Synthetic Materials (ie Carbon Fiber Mesh)Disadvantagesbull It often results in fibrous tissue formation bullNot adequate biomechanically bullOften the cause for synovitis in the joints

Osteocartiloginous GraftsAims to reconstruct jointsDisadvantagesbullUnless fresh cartilage is transplanted the cartilage is dead bullFresh grafts are not commonly used as they inevitably carry a risk of disease transmission bullCyropreserved grafts can survive for many years but ultimately deteriorate

Results of the Carticeltrade procedure have been encouraging although it is not always successful An analysis was done of the US and Swedish registry of 153 consecutive patients undergoing this procedure with follow-up from 1 week to 94 months The following results were obtainedbull Patients with clinical improvement 85bull Good or Excellent results 42 bull Good or Excellent results at 2 yearspersisting at 5 years post-op 97

Thus a total of 85 of patients showed some or complete improvement with theimplantation technique The Carticel procedure demonstrated good durability at 5-10 years out

CONCLUSIONS

CONCLUSIONS ACI Vs MACI No current evidence to justify aggressive treatment of

asymptomatic lesions with ACIMACI

Patients with full thickness symptomatic defects do poorly if left untreated

ACI and MACI lead to significant improvement in objective and patient reported clinical outcome scores for up to ten years(even among those with previous failed marrow stimulation techniques)

MACI has a superior rate of clinical improvement in comparison to ACI

Repair tissue may remodel and improve in quality with time

ACI and MACI comparable at 6 years

RECENT ADVANCESHYAFF 3D MATRIX

HYAFF biomaterialscontain high quantities ofderivatized HA

HA-richchondrocyte compatibleembryonic-like mileuconductive to regenerativehealing patterns

bull Non woven felt 2 mm thick fiber diameter 10 micronsbull Chondrocytes are isolated and passaged in culture on plasticdishes up to 3 weeksbull Cells are seeded for 2 weeks on HYAFF scaffold at a density of1 x 106 cm2 resulting in a total of 4 x 106 cm2 seeded cells pergraft

HYAFF-BASED SCAFFOLD

CHONDRONtrade

Uses a cell ndash gel mixture (includes collagen hyaluronic acid and fibrin) that has fast gelling properties (1 ndash 5 min) upon transplantation

This cell and gel mixture enable even cell distribution three-dimensionally moldable to fit irregular defect shape and applicable to a larger defectThus there is minimal surgical exposure and reduced surgery time

(three-dimensional reconstruction of a chondron from the growth plate of the murine long bone the model was generated from multiple sections imaged in an electron microscope plasma membranes are coloured green and internal organelles are visible within the top cell)

RECOVERY TO

HEALTHY ACTIVE LIFE

THANK YOU

• journal club (22-10-09)
• topic autologus chondrocyte implantation
• THE ROLE OF AUTOLOGOUS CHONDROCYTE IMPLANTATION (ACI) IN THE TR
• Slide 4
• AUTOLOGOUS CHONDROCYTE GRAFTS MULTICENTRIC TRIAL WITH 28 KNEE
• Slide 6
• Slide 7
• Articular Cartilage
• Hyaline Cartilage Structure 1048715The ldquostuffrdquo of cartilage
• Slide 11
• Cartilage Injury Occurs in Many Forms
• Articular Cartilage Defects a treatment challenge
• AND WHAT IS IN OUR BASKET
• SO IT LED US TO SEARCH OF MORE PROMISING OPTION
• Autologous Chondrocyte Implantation (ACI) BACKGROUND
• Identifying a Carticelreg Patient
• Identifying a Carticelreg Patienthelliphellip
• Pre-requisite for surgery
• Autologous Chondrocyte Implantation (ACI)
• Techniques
• ACIMACI Generic Method
• Slide 23
• Treatment with CARTICEL
• CARTICEL Manufacturing and Delivery
• Step 2 Implantation
• CARTICEL Implantation
• Periosteal Patch
• Slide 29
• Slide 30
• Aci steps summarised
• Slide 32
• Complications
• Slide 34
• Slide 35
• FOLLOW UP Biopsy
• FOLLOW UP MRI
• FOLLOW UP ARTHROSCOPIC
• Rehabilitation guidelines
• ACI Rehabilitation
• ACI Rehabilitation (2)
• COMPARISON WITH OTHER METHODS OF TREATMENTS
• COMPARISON WITH OTHER METHODS OF TREATMENTShelliphelliphellip
• COMPARISON WITH OTHER METHODS OF TREATMENTShelliphelliphellip (2)
• CONCLUSIONS
• Slide 46
• Recent advancesHYAFF 3D matrix
• HYAFF-based Scaffold
• CHONDRONtrade
• RECOVERY TO
• Slide 51

REHABILITATION GUIDELINES

Immobilization first 12-24 hours

(CPM) after 12-24 hours for about 4 weeks

Complete joint loading from about 5th week trochleapatellafrom about 8th week condyle Back to sports Low impact rarr within 6 monthsRepeated impact rarr from 8th monthHigh impact rarr from 10-12th month

ACI REHABILITATION

Weight bearingIt is recommended to keep you in non-weight bearing until the second week after surgery (ACI) You can increase the weight bearing gradually and you may be able to sustain your full weight bearing after 6 to 12 weeks from surgery

Range of motionRecovery on your ROM (Range of Motion) is gradually increased with a continuous passive motion (CPM) machine and may be completed to 140 degrees of ROM at 6 weeks to 12 weeks after surgery

ACI REHABILITATIONIndoor exerciseYou can strenghthen your muscles surrounding the knee joint with a four point exercise as well as isometric hamstring and squatting exercises from 4 weeks to 6 weeks after surgeryYou may start performing stationary bike activity without resistance and increase the resistance gradually

Outdoor exerciseAt 13 weeks after surgery you can start walking lightly and at 10 months after surgery you can perform jogging and then you may enjoy intensity exercise like playing tennis or volleyball from 18 months after surgery

Rehabilitation Goals at 12 weeks after ACIFull ROM (Range of Motion) Minimal edema level Minimal occasional pain Pain free tolerance to transitional phase exercise with adequate stability and motor control

COMPARISON WITH OTHER METHODS OF TREATMENTS

Autologous Chondrocyte Implantation Aims to increase the best condition for cartilage defectAdvantagesbullHyaline cartilage is formed bullPermanent reconstructed cartilage tissue bullMost valuable treatment

bullWith Fourth Generation ACI Use of cell ndash gel mixture (collagen hyaluronic acid and fibrin) has fast gelling properties (1 ndash 5 min) upon transplantation bullNo membrane or periosteal patch bullMinimal surgical exposure and reduced surgery time bullCorrects evenly irregular defect shapes bullApplicable to larger defects

COMPARISON WITH OTHER METHODS OF TREATMENTShelliphelliphellip

Abrasion arthroplastyAims to decrease the inflammation of the jointDisadvantagesbullRemoves many cartilage fragments from the jointbullSymptoms reoccur within one year

Drilling and MicrofractureAims to generate a healing responseDisadvantagesbullThe healing response in inadequate bullNo hyaline cartilage is formed but rather fibrocartilage bullHas a limited lifespan of approximately one year bullRapid deterioration after such procedures can be expected

COMPARISON WITH OTHER METHODS OF TREATMENTShelliphelliphellip

Perichondral ResurfacingDisadvantagesbullIsolated cartilage defects are often too large to be covered byh perichondrum bullLong term follow-up of such procedures indicate that the implants undergo endochondral ossification

Synthetic Materials (ie Carbon Fiber Mesh)Disadvantagesbull It often results in fibrous tissue formation bullNot adequate biomechanically bullOften the cause for synovitis in the joints

Osteocartiloginous GraftsAims to reconstruct jointsDisadvantagesbullUnless fresh cartilage is transplanted the cartilage is dead bullFresh grafts are not commonly used as they inevitably carry a risk of disease transmission bullCyropreserved grafts can survive for many years but ultimately deteriorate

Results of the Carticeltrade procedure have been encouraging although it is not always successful An analysis was done of the US and Swedish registry of 153 consecutive patients undergoing this procedure with follow-up from 1 week to 94 months The following results were obtainedbull Patients with clinical improvement 85bull Good or Excellent results 42 bull Good or Excellent results at 2 yearspersisting at 5 years post-op 97

Thus a total of 85 of patients showed some or complete improvement with theimplantation technique The Carticel procedure demonstrated good durability at 5-10 years out

CONCLUSIONS

CONCLUSIONS ACI Vs MACI No current evidence to justify aggressive treatment of

asymptomatic lesions with ACIMACI

Patients with full thickness symptomatic defects do poorly if left untreated

ACI and MACI lead to significant improvement in objective and patient reported clinical outcome scores for up to ten years(even among those with previous failed marrow stimulation techniques)

MACI has a superior rate of clinical improvement in comparison to ACI

Repair tissue may remodel and improve in quality with time

ACI and MACI comparable at 6 years

RECENT ADVANCESHYAFF 3D MATRIX

HYAFF biomaterialscontain high quantities ofderivatized HA

HA-richchondrocyte compatibleembryonic-like mileuconductive to regenerativehealing patterns

bull Non woven felt 2 mm thick fiber diameter 10 micronsbull Chondrocytes are isolated and passaged in culture on plasticdishes up to 3 weeksbull Cells are seeded for 2 weeks on HYAFF scaffold at a density of1 x 106 cm2 resulting in a total of 4 x 106 cm2 seeded cells pergraft

HYAFF-BASED SCAFFOLD

CHONDRONtrade

Uses a cell ndash gel mixture (includes collagen hyaluronic acid and fibrin) that has fast gelling properties (1 ndash 5 min) upon transplantation

This cell and gel mixture enable even cell distribution three-dimensionally moldable to fit irregular defect shape and applicable to a larger defectThus there is minimal surgical exposure and reduced surgery time

(three-dimensional reconstruction of a chondron from the growth plate of the murine long bone the model was generated from multiple sections imaged in an electron microscope plasma membranes are coloured green and internal organelles are visible within the top cell)

RECOVERY TO

HEALTHY ACTIVE LIFE

THANK YOU

• journal club (22-10-09)
• topic autologus chondrocyte implantation
• THE ROLE OF AUTOLOGOUS CHONDROCYTE IMPLANTATION (ACI) IN THE TR
• Slide 4
• AUTOLOGOUS CHONDROCYTE GRAFTS MULTICENTRIC TRIAL WITH 28 KNEE
• Slide 6
• Slide 7
• Articular Cartilage
• Hyaline Cartilage Structure 1048715The ldquostuffrdquo of cartilage
• Slide 11
• Cartilage Injury Occurs in Many Forms
• Articular Cartilage Defects a treatment challenge
• AND WHAT IS IN OUR BASKET
• SO IT LED US TO SEARCH OF MORE PROMISING OPTION
• Autologous Chondrocyte Implantation (ACI) BACKGROUND
• Identifying a Carticelreg Patient
• Identifying a Carticelreg Patienthelliphellip
• Pre-requisite for surgery
• Autologous Chondrocyte Implantation (ACI)
• Techniques
• ACIMACI Generic Method
• Slide 23
• Treatment with CARTICEL
• CARTICEL Manufacturing and Delivery
• Step 2 Implantation
• CARTICEL Implantation
• Periosteal Patch
• Slide 29
• Slide 30
• Aci steps summarised
• Slide 32
• Complications
• Slide 34
• Slide 35
• FOLLOW UP Biopsy
• FOLLOW UP MRI
• FOLLOW UP ARTHROSCOPIC
• Rehabilitation guidelines
• ACI Rehabilitation
• ACI Rehabilitation (2)
• COMPARISON WITH OTHER METHODS OF TREATMENTS
• COMPARISON WITH OTHER METHODS OF TREATMENTShelliphelliphellip
• COMPARISON WITH OTHER METHODS OF TREATMENTShelliphelliphellip (2)
• CONCLUSIONS
• Slide 46
• Recent advancesHYAFF 3D matrix
• HYAFF-based Scaffold
• CHONDRONtrade
• RECOVERY TO
• Slide 51

ACI REHABILITATION

Weight bearingIt is recommended to keep you in non-weight bearing until the second week after surgery (ACI) You can increase the weight bearing gradually and you may be able to sustain your full weight bearing after 6 to 12 weeks from surgery

Range of motionRecovery on your ROM (Range of Motion) is gradually increased with a continuous passive motion (CPM) machine and may be completed to 140 degrees of ROM at 6 weeks to 12 weeks after surgery

ACI REHABILITATIONIndoor exerciseYou can strenghthen your muscles surrounding the knee joint with a four point exercise as well as isometric hamstring and squatting exercises from 4 weeks to 6 weeks after surgeryYou may start performing stationary bike activity without resistance and increase the resistance gradually

Outdoor exerciseAt 13 weeks after surgery you can start walking lightly and at 10 months after surgery you can perform jogging and then you may enjoy intensity exercise like playing tennis or volleyball from 18 months after surgery

Rehabilitation Goals at 12 weeks after ACIFull ROM (Range of Motion) Minimal edema level Minimal occasional pain Pain free tolerance to transitional phase exercise with adequate stability and motor control

COMPARISON WITH OTHER METHODS OF TREATMENTS

Autologous Chondrocyte Implantation Aims to increase the best condition for cartilage defectAdvantagesbullHyaline cartilage is formed bullPermanent reconstructed cartilage tissue bullMost valuable treatment

bullWith Fourth Generation ACI Use of cell ndash gel mixture (collagen hyaluronic acid and fibrin) has fast gelling properties (1 ndash 5 min) upon transplantation bullNo membrane or periosteal patch bullMinimal surgical exposure and reduced surgery time bullCorrects evenly irregular defect shapes bullApplicable to larger defects

COMPARISON WITH OTHER METHODS OF TREATMENTShelliphelliphellip

Abrasion arthroplastyAims to decrease the inflammation of the jointDisadvantagesbullRemoves many cartilage fragments from the jointbullSymptoms reoccur within one year

Drilling and MicrofractureAims to generate a healing responseDisadvantagesbullThe healing response in inadequate bullNo hyaline cartilage is formed but rather fibrocartilage bullHas a limited lifespan of approximately one year bullRapid deterioration after such procedures can be expected

COMPARISON WITH OTHER METHODS OF TREATMENTShelliphelliphellip

Perichondral ResurfacingDisadvantagesbullIsolated cartilage defects are often too large to be covered byh perichondrum bullLong term follow-up of such procedures indicate that the implants undergo endochondral ossification

Synthetic Materials (ie Carbon Fiber Mesh)Disadvantagesbull It often results in fibrous tissue formation bullNot adequate biomechanically bullOften the cause for synovitis in the joints

Osteocartiloginous GraftsAims to reconstruct jointsDisadvantagesbullUnless fresh cartilage is transplanted the cartilage is dead bullFresh grafts are not commonly used as they inevitably carry a risk of disease transmission bullCyropreserved grafts can survive for many years but ultimately deteriorate

Results of the Carticeltrade procedure have been encouraging although it is not always successful An analysis was done of the US and Swedish registry of 153 consecutive patients undergoing this procedure with follow-up from 1 week to 94 months The following results were obtainedbull Patients with clinical improvement 85bull Good or Excellent results 42 bull Good or Excellent results at 2 yearspersisting at 5 years post-op 97

Thus a total of 85 of patients showed some or complete improvement with theimplantation technique The Carticel procedure demonstrated good durability at 5-10 years out

CONCLUSIONS

CONCLUSIONS ACI Vs MACI No current evidence to justify aggressive treatment of

asymptomatic lesions with ACIMACI

Patients with full thickness symptomatic defects do poorly if left untreated

ACI and MACI lead to significant improvement in objective and patient reported clinical outcome scores for up to ten years(even among those with previous failed marrow stimulation techniques)

MACI has a superior rate of clinical improvement in comparison to ACI

Repair tissue may remodel and improve in quality with time

ACI and MACI comparable at 6 years

RECENT ADVANCESHYAFF 3D MATRIX

HYAFF biomaterialscontain high quantities ofderivatized HA

HA-richchondrocyte compatibleembryonic-like mileuconductive to regenerativehealing patterns

bull Non woven felt 2 mm thick fiber diameter 10 micronsbull Chondrocytes are isolated and passaged in culture on plasticdishes up to 3 weeksbull Cells are seeded for 2 weeks on HYAFF scaffold at a density of1 x 106 cm2 resulting in a total of 4 x 106 cm2 seeded cells pergraft

HYAFF-BASED SCAFFOLD

CHONDRONtrade

Uses a cell ndash gel mixture (includes collagen hyaluronic acid and fibrin) that has fast gelling properties (1 ndash 5 min) upon transplantation

This cell and gel mixture enable even cell distribution three-dimensionally moldable to fit irregular defect shape and applicable to a larger defectThus there is minimal surgical exposure and reduced surgery time

(three-dimensional reconstruction of a chondron from the growth plate of the murine long bone the model was generated from multiple sections imaged in an electron microscope plasma membranes are coloured green and internal organelles are visible within the top cell)

RECOVERY TO

HEALTHY ACTIVE LIFE

THANK YOU

• journal club (22-10-09)
• topic autologus chondrocyte implantation
• THE ROLE OF AUTOLOGOUS CHONDROCYTE IMPLANTATION (ACI) IN THE TR
• Slide 4
• AUTOLOGOUS CHONDROCYTE GRAFTS MULTICENTRIC TRIAL WITH 28 KNEE
• Slide 6
• Slide 7
• Articular Cartilage
• Hyaline Cartilage Structure 1048715The ldquostuffrdquo of cartilage
• Slide 11
• Cartilage Injury Occurs in Many Forms
• Articular Cartilage Defects a treatment challenge
• AND WHAT IS IN OUR BASKET
• SO IT LED US TO SEARCH OF MORE PROMISING OPTION
• Autologous Chondrocyte Implantation (ACI) BACKGROUND
• Identifying a Carticelreg Patient
• Identifying a Carticelreg Patienthelliphellip
• Pre-requisite for surgery
• Autologous Chondrocyte Implantation (ACI)
• Techniques
• ACIMACI Generic Method
• Slide 23
• Treatment with CARTICEL
• CARTICEL Manufacturing and Delivery
• Step 2 Implantation
• CARTICEL Implantation
• Periosteal Patch
• Slide 29
• Slide 30
• Aci steps summarised
• Slide 32
• Complications
• Slide 34
• Slide 35
• FOLLOW UP Biopsy
• FOLLOW UP MRI
• FOLLOW UP ARTHROSCOPIC
• Rehabilitation guidelines
• ACI Rehabilitation
• ACI Rehabilitation (2)
• COMPARISON WITH OTHER METHODS OF TREATMENTS
• COMPARISON WITH OTHER METHODS OF TREATMENTShelliphelliphellip
• COMPARISON WITH OTHER METHODS OF TREATMENTShelliphelliphellip (2)
• CONCLUSIONS
• Slide 46
• Recent advancesHYAFF 3D matrix
• HYAFF-based Scaffold
• CHONDRONtrade
• RECOVERY TO
• Slide 51

ACI REHABILITATIONIndoor exerciseYou can strenghthen your muscles surrounding the knee joint with a four point exercise as well as isometric hamstring and squatting exercises from 4 weeks to 6 weeks after surgeryYou may start performing stationary bike activity without resistance and increase the resistance gradually

Outdoor exerciseAt 13 weeks after surgery you can start walking lightly and at 10 months after surgery you can perform jogging and then you may enjoy intensity exercise like playing tennis or volleyball from 18 months after surgery

Rehabilitation Goals at 12 weeks after ACIFull ROM (Range of Motion) Minimal edema level Minimal occasional pain Pain free tolerance to transitional phase exercise with adequate stability and motor control

COMPARISON WITH OTHER METHODS OF TREATMENTS

Autologous Chondrocyte Implantation Aims to increase the best condition for cartilage defectAdvantagesbullHyaline cartilage is formed bullPermanent reconstructed cartilage tissue bullMost valuable treatment

bullWith Fourth Generation ACI Use of cell ndash gel mixture (collagen hyaluronic acid and fibrin) has fast gelling properties (1 ndash 5 min) upon transplantation bullNo membrane or periosteal patch bullMinimal surgical exposure and reduced surgery time bullCorrects evenly irregular defect shapes bullApplicable to larger defects

COMPARISON WITH OTHER METHODS OF TREATMENTShelliphelliphellip

Abrasion arthroplastyAims to decrease the inflammation of the jointDisadvantagesbullRemoves many cartilage fragments from the jointbullSymptoms reoccur within one year

Drilling and MicrofractureAims to generate a healing responseDisadvantagesbullThe healing response in inadequate bullNo hyaline cartilage is formed but rather fibrocartilage bullHas a limited lifespan of approximately one year bullRapid deterioration after such procedures can be expected

COMPARISON WITH OTHER METHODS OF TREATMENTShelliphelliphellip

Perichondral ResurfacingDisadvantagesbullIsolated cartilage defects are often too large to be covered byh perichondrum bullLong term follow-up of such procedures indicate that the implants undergo endochondral ossification

Synthetic Materials (ie Carbon Fiber Mesh)Disadvantagesbull It often results in fibrous tissue formation bullNot adequate biomechanically bullOften the cause for synovitis in the joints

Osteocartiloginous GraftsAims to reconstruct jointsDisadvantagesbullUnless fresh cartilage is transplanted the cartilage is dead bullFresh grafts are not commonly used as they inevitably carry a risk of disease transmission bullCyropreserved grafts can survive for many years but ultimately deteriorate

Results of the Carticeltrade procedure have been encouraging although it is not always successful An analysis was done of the US and Swedish registry of 153 consecutive patients undergoing this procedure with follow-up from 1 week to 94 months The following results were obtainedbull Patients with clinical improvement 85bull Good or Excellent results 42 bull Good or Excellent results at 2 yearspersisting at 5 years post-op 97

Thus a total of 85 of patients showed some or complete improvement with theimplantation technique The Carticel procedure demonstrated good durability at 5-10 years out

CONCLUSIONS

CONCLUSIONS ACI Vs MACI No current evidence to justify aggressive treatment of

asymptomatic lesions with ACIMACI

Patients with full thickness symptomatic defects do poorly if left untreated

ACI and MACI lead to significant improvement in objective and patient reported clinical outcome scores for up to ten years(even among those with previous failed marrow stimulation techniques)

MACI has a superior rate of clinical improvement in comparison to ACI

Repair tissue may remodel and improve in quality with time

ACI and MACI comparable at 6 years

RECENT ADVANCESHYAFF 3D MATRIX

HYAFF biomaterialscontain high quantities ofderivatized HA

HA-richchondrocyte compatibleembryonic-like mileuconductive to regenerativehealing patterns

bull Non woven felt 2 mm thick fiber diameter 10 micronsbull Chondrocytes are isolated and passaged in culture on plasticdishes up to 3 weeksbull Cells are seeded for 2 weeks on HYAFF scaffold at a density of1 x 106 cm2 resulting in a total of 4 x 106 cm2 seeded cells pergraft

HYAFF-BASED SCAFFOLD

CHONDRONtrade

Uses a cell ndash gel mixture (includes collagen hyaluronic acid and fibrin) that has fast gelling properties (1 ndash 5 min) upon transplantation

This cell and gel mixture enable even cell distribution three-dimensionally moldable to fit irregular defect shape and applicable to a larger defectThus there is minimal surgical exposure and reduced surgery time

(three-dimensional reconstruction of a chondron from the growth plate of the murine long bone the model was generated from multiple sections imaged in an electron microscope plasma membranes are coloured green and internal organelles are visible within the top cell)

RECOVERY TO

HEALTHY ACTIVE LIFE

THANK YOU

• journal club (22-10-09)
• topic autologus chondrocyte implantation
• THE ROLE OF AUTOLOGOUS CHONDROCYTE IMPLANTATION (ACI) IN THE TR
• Slide 4
• AUTOLOGOUS CHONDROCYTE GRAFTS MULTICENTRIC TRIAL WITH 28 KNEE
• Slide 6
• Slide 7
• Articular Cartilage
• Hyaline Cartilage Structure 1048715The ldquostuffrdquo of cartilage
• Slide 11
• Cartilage Injury Occurs in Many Forms
• Articular Cartilage Defects a treatment challenge
• AND WHAT IS IN OUR BASKET
• SO IT LED US TO SEARCH OF MORE PROMISING OPTION
• Autologous Chondrocyte Implantation (ACI) BACKGROUND
• Identifying a Carticelreg Patient
• Identifying a Carticelreg Patienthelliphellip
• Pre-requisite for surgery
• Autologous Chondrocyte Implantation (ACI)
• Techniques
• ACIMACI Generic Method
• Slide 23
• Treatment with CARTICEL
• CARTICEL Manufacturing and Delivery
• Step 2 Implantation
• CARTICEL Implantation
• Periosteal Patch
• Slide 29
• Slide 30
• Aci steps summarised
• Slide 32
• Complications
• Slide 34
• Slide 35
• FOLLOW UP Biopsy
• FOLLOW UP MRI
• FOLLOW UP ARTHROSCOPIC
• Rehabilitation guidelines
• ACI Rehabilitation
• ACI Rehabilitation (2)
• COMPARISON WITH OTHER METHODS OF TREATMENTS
• COMPARISON WITH OTHER METHODS OF TREATMENTShelliphelliphellip
• COMPARISON WITH OTHER METHODS OF TREATMENTShelliphelliphellip (2)
• CONCLUSIONS
• Slide 46
• Recent advancesHYAFF 3D matrix
• HYAFF-based Scaffold
• CHONDRONtrade
• RECOVERY TO
• Slide 51

COMPARISON WITH OTHER METHODS OF TREATMENTS

Autologous Chondrocyte Implantation Aims to increase the best condition for cartilage defectAdvantagesbullHyaline cartilage is formed bullPermanent reconstructed cartilage tissue bullMost valuable treatment

bullWith Fourth Generation ACI Use of cell ndash gel mixture (collagen hyaluronic acid and fibrin) has fast gelling properties (1 ndash 5 min) upon transplantation bullNo membrane or periosteal patch bullMinimal surgical exposure and reduced surgery time bullCorrects evenly irregular defect shapes bullApplicable to larger defects

COMPARISON WITH OTHER METHODS OF TREATMENTShelliphelliphellip

Abrasion arthroplastyAims to decrease the inflammation of the jointDisadvantagesbullRemoves many cartilage fragments from the jointbullSymptoms reoccur within one year

Drilling and MicrofractureAims to generate a healing responseDisadvantagesbullThe healing response in inadequate bullNo hyaline cartilage is formed but rather fibrocartilage bullHas a limited lifespan of approximately one year bullRapid deterioration after such procedures can be expected

COMPARISON WITH OTHER METHODS OF TREATMENTShelliphelliphellip

Perichondral ResurfacingDisadvantagesbullIsolated cartilage defects are often too large to be covered byh perichondrum bullLong term follow-up of such procedures indicate that the implants undergo endochondral ossification

Synthetic Materials (ie Carbon Fiber Mesh)Disadvantagesbull It often results in fibrous tissue formation bullNot adequate biomechanically bullOften the cause for synovitis in the joints

Osteocartiloginous GraftsAims to reconstruct jointsDisadvantagesbullUnless fresh cartilage is transplanted the cartilage is dead bullFresh grafts are not commonly used as they inevitably carry a risk of disease transmission bullCyropreserved grafts can survive for many years but ultimately deteriorate

Results of the Carticeltrade procedure have been encouraging although it is not always successful An analysis was done of the US and Swedish registry of 153 consecutive patients undergoing this procedure with follow-up from 1 week to 94 months The following results were obtainedbull Patients with clinical improvement 85bull Good or Excellent results 42 bull Good or Excellent results at 2 yearspersisting at 5 years post-op 97

Thus a total of 85 of patients showed some or complete improvement with theimplantation technique The Carticel procedure demonstrated good durability at 5-10 years out

CONCLUSIONS

CONCLUSIONS ACI Vs MACI No current evidence to justify aggressive treatment of

asymptomatic lesions with ACIMACI

Patients with full thickness symptomatic defects do poorly if left untreated

ACI and MACI lead to significant improvement in objective and patient reported clinical outcome scores for up to ten years(even among those with previous failed marrow stimulation techniques)

MACI has a superior rate of clinical improvement in comparison to ACI

Repair tissue may remodel and improve in quality with time

ACI and MACI comparable at 6 years

RECENT ADVANCESHYAFF 3D MATRIX

HYAFF biomaterialscontain high quantities ofderivatized HA

HA-richchondrocyte compatibleembryonic-like mileuconductive to regenerativehealing patterns

bull Non woven felt 2 mm thick fiber diameter 10 micronsbull Chondrocytes are isolated and passaged in culture on plasticdishes up to 3 weeksbull Cells are seeded for 2 weeks on HYAFF scaffold at a density of1 x 106 cm2 resulting in a total of 4 x 106 cm2 seeded cells pergraft

HYAFF-BASED SCAFFOLD

CHONDRONtrade

Uses a cell ndash gel mixture (includes collagen hyaluronic acid and fibrin) that has fast gelling properties (1 ndash 5 min) upon transplantation

This cell and gel mixture enable even cell distribution three-dimensionally moldable to fit irregular defect shape and applicable to a larger defectThus there is minimal surgical exposure and reduced surgery time

(three-dimensional reconstruction of a chondron from the growth plate of the murine long bone the model was generated from multiple sections imaged in an electron microscope plasma membranes are coloured green and internal organelles are visible within the top cell)

RECOVERY TO

HEALTHY ACTIVE LIFE

THANK YOU

• journal club (22-10-09)
• topic autologus chondrocyte implantation
• THE ROLE OF AUTOLOGOUS CHONDROCYTE IMPLANTATION (ACI) IN THE TR
• Slide 4
• AUTOLOGOUS CHONDROCYTE GRAFTS MULTICENTRIC TRIAL WITH 28 KNEE
• Slide 6
• Slide 7
• Articular Cartilage
• Hyaline Cartilage Structure 1048715The ldquostuffrdquo of cartilage
• Slide 11
• Cartilage Injury Occurs in Many Forms
• Articular Cartilage Defects a treatment challenge
• AND WHAT IS IN OUR BASKET
• SO IT LED US TO SEARCH OF MORE PROMISING OPTION
• Autologous Chondrocyte Implantation (ACI) BACKGROUND
• Identifying a Carticelreg Patient
• Identifying a Carticelreg Patienthelliphellip
• Pre-requisite for surgery
• Autologous Chondrocyte Implantation (ACI)
• Techniques
• ACIMACI Generic Method
• Slide 23
• Treatment with CARTICEL
• CARTICEL Manufacturing and Delivery
• Step 2 Implantation
• CARTICEL Implantation
• Periosteal Patch
• Slide 29
• Slide 30
• Aci steps summarised
• Slide 32
• Complications
• Slide 34
• Slide 35
• FOLLOW UP Biopsy
• FOLLOW UP MRI
• FOLLOW UP ARTHROSCOPIC
• Rehabilitation guidelines
• ACI Rehabilitation
• ACI Rehabilitation (2)
• COMPARISON WITH OTHER METHODS OF TREATMENTS
• COMPARISON WITH OTHER METHODS OF TREATMENTShelliphelliphellip
• COMPARISON WITH OTHER METHODS OF TREATMENTShelliphelliphellip (2)
• CONCLUSIONS
• Slide 46
• Recent advancesHYAFF 3D matrix
• HYAFF-based Scaffold
• CHONDRONtrade
• RECOVERY TO
• Slide 51

COMPARISON WITH OTHER METHODS OF TREATMENTShelliphelliphellip

Abrasion arthroplastyAims to decrease the inflammation of the jointDisadvantagesbullRemoves many cartilage fragments from the jointbullSymptoms reoccur within one year

Drilling and MicrofractureAims to generate a healing responseDisadvantagesbullThe healing response in inadequate bullNo hyaline cartilage is formed but rather fibrocartilage bullHas a limited lifespan of approximately one year bullRapid deterioration after such procedures can be expected

COMPARISON WITH OTHER METHODS OF TREATMENTShelliphelliphellip

Perichondral ResurfacingDisadvantagesbullIsolated cartilage defects are often too large to be covered byh perichondrum bullLong term follow-up of such procedures indicate that the implants undergo endochondral ossification

Synthetic Materials (ie Carbon Fiber Mesh)Disadvantagesbull It often results in fibrous tissue formation bullNot adequate biomechanically bullOften the cause for synovitis in the joints

Osteocartiloginous GraftsAims to reconstruct jointsDisadvantagesbullUnless fresh cartilage is transplanted the cartilage is dead bullFresh grafts are not commonly used as they inevitably carry a risk of disease transmission bullCyropreserved grafts can survive for many years but ultimately deteriorate

Results of the Carticeltrade procedure have been encouraging although it is not always successful An analysis was done of the US and Swedish registry of 153 consecutive patients undergoing this procedure with follow-up from 1 week to 94 months The following results were obtainedbull Patients with clinical improvement 85bull Good or Excellent results 42 bull Good or Excellent results at 2 yearspersisting at 5 years post-op 97

Thus a total of 85 of patients showed some or complete improvement with theimplantation technique The Carticel procedure demonstrated good durability at 5-10 years out

CONCLUSIONS

CONCLUSIONS ACI Vs MACI No current evidence to justify aggressive treatment of

asymptomatic lesions with ACIMACI

Patients with full thickness symptomatic defects do poorly if left untreated

ACI and MACI lead to significant improvement in objective and patient reported clinical outcome scores for up to ten years(even among those with previous failed marrow stimulation techniques)

MACI has a superior rate of clinical improvement in comparison to ACI

Repair tissue may remodel and improve in quality with time

ACI and MACI comparable at 6 years

RECENT ADVANCESHYAFF 3D MATRIX

HYAFF biomaterialscontain high quantities ofderivatized HA

HA-richchondrocyte compatibleembryonic-like mileuconductive to regenerativehealing patterns

bull Non woven felt 2 mm thick fiber diameter 10 micronsbull Chondrocytes are isolated and passaged in culture on plasticdishes up to 3 weeksbull Cells are seeded for 2 weeks on HYAFF scaffold at a density of1 x 106 cm2 resulting in a total of 4 x 106 cm2 seeded cells pergraft

HYAFF-BASED SCAFFOLD

CHONDRONtrade

Uses a cell ndash gel mixture (includes collagen hyaluronic acid and fibrin) that has fast gelling properties (1 ndash 5 min) upon transplantation

This cell and gel mixture enable even cell distribution three-dimensionally moldable to fit irregular defect shape and applicable to a larger defectThus there is minimal surgical exposure and reduced surgery time

(three-dimensional reconstruction of a chondron from the growth plate of the murine long bone the model was generated from multiple sections imaged in an electron microscope plasma membranes are coloured green and internal organelles are visible within the top cell)

RECOVERY TO

HEALTHY ACTIVE LIFE

THANK YOU

• journal club (22-10-09)
• topic autologus chondrocyte implantation
• THE ROLE OF AUTOLOGOUS CHONDROCYTE IMPLANTATION (ACI) IN THE TR
• Slide 4
• AUTOLOGOUS CHONDROCYTE GRAFTS MULTICENTRIC TRIAL WITH 28 KNEE
• Slide 6
• Slide 7
• Articular Cartilage
• Hyaline Cartilage Structure 1048715The ldquostuffrdquo of cartilage
• Slide 11
• Cartilage Injury Occurs in Many Forms
• Articular Cartilage Defects a treatment challenge
• AND WHAT IS IN OUR BASKET
• SO IT LED US TO SEARCH OF MORE PROMISING OPTION
• Autologous Chondrocyte Implantation (ACI) BACKGROUND
• Identifying a Carticelreg Patient
• Identifying a Carticelreg Patienthelliphellip
• Pre-requisite for surgery
• Autologous Chondrocyte Implantation (ACI)
• Techniques
• ACIMACI Generic Method
• Slide 23
• Treatment with CARTICEL
• CARTICEL Manufacturing and Delivery
• Step 2 Implantation
• CARTICEL Implantation
• Periosteal Patch
• Slide 29
• Slide 30
• Aci steps summarised
• Slide 32
• Complications
• Slide 34
• Slide 35
• FOLLOW UP Biopsy
• FOLLOW UP MRI
• FOLLOW UP ARTHROSCOPIC
• Rehabilitation guidelines
• ACI Rehabilitation
• ACI Rehabilitation (2)
• COMPARISON WITH OTHER METHODS OF TREATMENTS
• COMPARISON WITH OTHER METHODS OF TREATMENTShelliphelliphellip
• COMPARISON WITH OTHER METHODS OF TREATMENTShelliphelliphellip (2)
• CONCLUSIONS
• Slide 46
• Recent advancesHYAFF 3D matrix
• HYAFF-based Scaffold
• CHONDRONtrade
• RECOVERY TO
• Slide 51

COMPARISON WITH OTHER METHODS OF TREATMENTShelliphelliphellip

Perichondral ResurfacingDisadvantagesbullIsolated cartilage defects are often too large to be covered byh perichondrum bullLong term follow-up of such procedures indicate that the implants undergo endochondral ossification

Synthetic Materials (ie Carbon Fiber Mesh)Disadvantagesbull It often results in fibrous tissue formation bullNot adequate biomechanically bullOften the cause for synovitis in the joints

Osteocartiloginous GraftsAims to reconstruct jointsDisadvantagesbullUnless fresh cartilage is transplanted the cartilage is dead bullFresh grafts are not commonly used as they inevitably carry a risk of disease transmission bullCyropreserved grafts can survive for many years but ultimately deteriorate

Results of the Carticeltrade procedure have been encouraging although it is not always successful An analysis was done of the US and Swedish registry of 153 consecutive patients undergoing this procedure with follow-up from 1 week to 94 months The following results were obtainedbull Patients with clinical improvement 85bull Good or Excellent results 42 bull Good or Excellent results at 2 yearspersisting at 5 years post-op 97

Thus a total of 85 of patients showed some or complete improvement with theimplantation technique The Carticel procedure demonstrated good durability at 5-10 years out

CONCLUSIONS

CONCLUSIONS ACI Vs MACI No current evidence to justify aggressive treatment of

asymptomatic lesions with ACIMACI

Patients with full thickness symptomatic defects do poorly if left untreated

ACI and MACI lead to significant improvement in objective and patient reported clinical outcome scores for up to ten years(even among those with previous failed marrow stimulation techniques)

MACI has a superior rate of clinical improvement in comparison to ACI

Repair tissue may remodel and improve in quality with time

ACI and MACI comparable at 6 years

RECENT ADVANCESHYAFF 3D MATRIX

HYAFF biomaterialscontain high quantities ofderivatized HA

HA-richchondrocyte compatibleembryonic-like mileuconductive to regenerativehealing patterns

bull Non woven felt 2 mm thick fiber diameter 10 micronsbull Chondrocytes are isolated and passaged in culture on plasticdishes up to 3 weeksbull Cells are seeded for 2 weeks on HYAFF scaffold at a density of1 x 106 cm2 resulting in a total of 4 x 106 cm2 seeded cells pergraft

HYAFF-BASED SCAFFOLD

CHONDRONtrade

Uses a cell ndash gel mixture (includes collagen hyaluronic acid and fibrin) that has fast gelling properties (1 ndash 5 min) upon transplantation

This cell and gel mixture enable even cell distribution three-dimensionally moldable to fit irregular defect shape and applicable to a larger defectThus there is minimal surgical exposure and reduced surgery time

(three-dimensional reconstruction of a chondron from the growth plate of the murine long bone the model was generated from multiple sections imaged in an electron microscope plasma membranes are coloured green and internal organelles are visible within the top cell)

RECOVERY TO

HEALTHY ACTIVE LIFE

THANK YOU

• journal club (22-10-09)
• topic autologus chondrocyte implantation
• THE ROLE OF AUTOLOGOUS CHONDROCYTE IMPLANTATION (ACI) IN THE TR
• Slide 4
• AUTOLOGOUS CHONDROCYTE GRAFTS MULTICENTRIC TRIAL WITH 28 KNEE
• Slide 6
• Slide 7
• Articular Cartilage
• Hyaline Cartilage Structure 1048715The ldquostuffrdquo of cartilage
• Slide 11
• Cartilage Injury Occurs in Many Forms
• Articular Cartilage Defects a treatment challenge
• AND WHAT IS IN OUR BASKET
• SO IT LED US TO SEARCH OF MORE PROMISING OPTION
• Autologous Chondrocyte Implantation (ACI) BACKGROUND
• Identifying a Carticelreg Patient
• Identifying a Carticelreg Patienthelliphellip
• Pre-requisite for surgery
• Autologous Chondrocyte Implantation (ACI)
• Techniques
• ACIMACI Generic Method
• Slide 23
• Treatment with CARTICEL
• CARTICEL Manufacturing and Delivery
• Step 2 Implantation
• CARTICEL Implantation
• Periosteal Patch
• Slide 29
• Slide 30
• Aci steps summarised
• Slide 32
• Complications
• Slide 34
• Slide 35
• FOLLOW UP Biopsy
• FOLLOW UP MRI
• FOLLOW UP ARTHROSCOPIC
• Rehabilitation guidelines
• ACI Rehabilitation
• ACI Rehabilitation (2)
• COMPARISON WITH OTHER METHODS OF TREATMENTS
• COMPARISON WITH OTHER METHODS OF TREATMENTShelliphelliphellip
• COMPARISON WITH OTHER METHODS OF TREATMENTShelliphelliphellip (2)
• CONCLUSIONS
• Slide 46
• Recent advancesHYAFF 3D matrix
• HYAFF-based Scaffold
• CHONDRONtrade
• RECOVERY TO
• Slide 51

Results of the Carticeltrade procedure have been encouraging although it is not always successful An analysis was done of the US and Swedish registry of 153 consecutive patients undergoing this procedure with follow-up from 1 week to 94 months The following results were obtainedbull Patients with clinical improvement 85bull Good or Excellent results 42 bull Good or Excellent results at 2 yearspersisting at 5 years post-op 97

Thus a total of 85 of patients showed some or complete improvement with theimplantation technique The Carticel procedure demonstrated good durability at 5-10 years out

CONCLUSIONS

CONCLUSIONS ACI Vs MACI No current evidence to justify aggressive treatment of

asymptomatic lesions with ACIMACI

Patients with full thickness symptomatic defects do poorly if left untreated

ACI and MACI lead to significant improvement in objective and patient reported clinical outcome scores for up to ten years(even among those with previous failed marrow stimulation techniques)

MACI has a superior rate of clinical improvement in comparison to ACI

Repair tissue may remodel and improve in quality with time

ACI and MACI comparable at 6 years

RECENT ADVANCESHYAFF 3D MATRIX

HYAFF biomaterialscontain high quantities ofderivatized HA

HA-richchondrocyte compatibleembryonic-like mileuconductive to regenerativehealing patterns

bull Non woven felt 2 mm thick fiber diameter 10 micronsbull Chondrocytes are isolated and passaged in culture on plasticdishes up to 3 weeksbull Cells are seeded for 2 weeks on HYAFF scaffold at a density of1 x 106 cm2 resulting in a total of 4 x 106 cm2 seeded cells pergraft

HYAFF-BASED SCAFFOLD

CHONDRONtrade

Uses a cell ndash gel mixture (includes collagen hyaluronic acid and fibrin) that has fast gelling properties (1 ndash 5 min) upon transplantation

This cell and gel mixture enable even cell distribution three-dimensionally moldable to fit irregular defect shape and applicable to a larger defectThus there is minimal surgical exposure and reduced surgery time

(three-dimensional reconstruction of a chondron from the growth plate of the murine long bone the model was generated from multiple sections imaged in an electron microscope plasma membranes are coloured green and internal organelles are visible within the top cell)

RECOVERY TO

HEALTHY ACTIVE LIFE

THANK YOU

• journal club (22-10-09)
• topic autologus chondrocyte implantation
• THE ROLE OF AUTOLOGOUS CHONDROCYTE IMPLANTATION (ACI) IN THE TR
• Slide 4
• AUTOLOGOUS CHONDROCYTE GRAFTS MULTICENTRIC TRIAL WITH 28 KNEE
• Slide 6
• Slide 7
• Articular Cartilage
• Hyaline Cartilage Structure 1048715The ldquostuffrdquo of cartilage
• Slide 11
• Cartilage Injury Occurs in Many Forms
• Articular Cartilage Defects a treatment challenge
• AND WHAT IS IN OUR BASKET
• SO IT LED US TO SEARCH OF MORE PROMISING OPTION
• Autologous Chondrocyte Implantation (ACI) BACKGROUND
• Identifying a Carticelreg Patient
• Identifying a Carticelreg Patienthelliphellip
• Pre-requisite for surgery
• Autologous Chondrocyte Implantation (ACI)
• Techniques
• ACIMACI Generic Method
• Slide 23
• Treatment with CARTICEL
• CARTICEL Manufacturing and Delivery
• Step 2 Implantation
• CARTICEL Implantation
• Periosteal Patch
• Slide 29
• Slide 30
• Aci steps summarised
• Slide 32
• Complications
• Slide 34
• Slide 35
• FOLLOW UP Biopsy
• FOLLOW UP MRI
• FOLLOW UP ARTHROSCOPIC
• Rehabilitation guidelines
• ACI Rehabilitation
• ACI Rehabilitation (2)
• COMPARISON WITH OTHER METHODS OF TREATMENTS
• COMPARISON WITH OTHER METHODS OF TREATMENTShelliphelliphellip
• COMPARISON WITH OTHER METHODS OF TREATMENTShelliphelliphellip (2)
• CONCLUSIONS
• Slide 46
• Recent advancesHYAFF 3D matrix
• HYAFF-based Scaffold
• CHONDRONtrade
• RECOVERY TO
• Slide 51

CONCLUSIONS ACI Vs MACI No current evidence to justify aggressive treatment of

asymptomatic lesions with ACIMACI

Patients with full thickness symptomatic defects do poorly if left untreated

ACI and MACI lead to significant improvement in objective and patient reported clinical outcome scores for up to ten years(even among those with previous failed marrow stimulation techniques)

MACI has a superior rate of clinical improvement in comparison to ACI

Repair tissue may remodel and improve in quality with time

ACI and MACI comparable at 6 years

RECENT ADVANCESHYAFF 3D MATRIX

HYAFF biomaterialscontain high quantities ofderivatized HA

HA-richchondrocyte compatibleembryonic-like mileuconductive to regenerativehealing patterns

bull Non woven felt 2 mm thick fiber diameter 10 micronsbull Chondrocytes are isolated and passaged in culture on plasticdishes up to 3 weeksbull Cells are seeded for 2 weeks on HYAFF scaffold at a density of1 x 106 cm2 resulting in a total of 4 x 106 cm2 seeded cells pergraft

HYAFF-BASED SCAFFOLD

CHONDRONtrade

Uses a cell ndash gel mixture (includes collagen hyaluronic acid and fibrin) that has fast gelling properties (1 ndash 5 min) upon transplantation

This cell and gel mixture enable even cell distribution three-dimensionally moldable to fit irregular defect shape and applicable to a larger defectThus there is minimal surgical exposure and reduced surgery time

(three-dimensional reconstruction of a chondron from the growth plate of the murine long bone the model was generated from multiple sections imaged in an electron microscope plasma membranes are coloured green and internal organelles are visible within the top cell)

RECOVERY TO

HEALTHY ACTIVE LIFE

THANK YOU

• journal club (22-10-09)
• topic autologus chondrocyte implantation
• THE ROLE OF AUTOLOGOUS CHONDROCYTE IMPLANTATION (ACI) IN THE TR
• Slide 4
• AUTOLOGOUS CHONDROCYTE GRAFTS MULTICENTRIC TRIAL WITH 28 KNEE
• Slide 6
• Slide 7
• Articular Cartilage
• Hyaline Cartilage Structure 1048715The ldquostuffrdquo of cartilage
• Slide 11
• Cartilage Injury Occurs in Many Forms
• Articular Cartilage Defects a treatment challenge
• AND WHAT IS IN OUR BASKET
• SO IT LED US TO SEARCH OF MORE PROMISING OPTION
• Autologous Chondrocyte Implantation (ACI) BACKGROUND
• Identifying a Carticelreg Patient
• Identifying a Carticelreg Patienthelliphellip
• Pre-requisite for surgery
• Autologous Chondrocyte Implantation (ACI)
• Techniques
• ACIMACI Generic Method
• Slide 23
• Treatment with CARTICEL
• CARTICEL Manufacturing and Delivery
• Step 2 Implantation
• CARTICEL Implantation
• Periosteal Patch
• Slide 29
• Slide 30
• Aci steps summarised
• Slide 32
• Complications
• Slide 34
• Slide 35
• FOLLOW UP Biopsy
• FOLLOW UP MRI
• FOLLOW UP ARTHROSCOPIC
• Rehabilitation guidelines
• ACI Rehabilitation
• ACI Rehabilitation (2)
• COMPARISON WITH OTHER METHODS OF TREATMENTS
• COMPARISON WITH OTHER METHODS OF TREATMENTShelliphelliphellip
• COMPARISON WITH OTHER METHODS OF TREATMENTShelliphelliphellip (2)
• CONCLUSIONS
• Slide 46
• Recent advancesHYAFF 3D matrix
• HYAFF-based Scaffold
• CHONDRONtrade
• RECOVERY TO
• Slide 51

RECENT ADVANCESHYAFF 3D MATRIX

HYAFF biomaterialscontain high quantities ofderivatized HA

HA-richchondrocyte compatibleembryonic-like mileuconductive to regenerativehealing patterns

bull Non woven felt 2 mm thick fiber diameter 10 micronsbull Chondrocytes are isolated and passaged in culture on plasticdishes up to 3 weeksbull Cells are seeded for 2 weeks on HYAFF scaffold at a density of1 x 106 cm2 resulting in a total of 4 x 106 cm2 seeded cells pergraft

HYAFF-BASED SCAFFOLD

CHONDRONtrade

Uses a cell ndash gel mixture (includes collagen hyaluronic acid and fibrin) that has fast gelling properties (1 ndash 5 min) upon transplantation

This cell and gel mixture enable even cell distribution three-dimensionally moldable to fit irregular defect shape and applicable to a larger defectThus there is minimal surgical exposure and reduced surgery time

(three-dimensional reconstruction of a chondron from the growth plate of the murine long bone the model was generated from multiple sections imaged in an electron microscope plasma membranes are coloured green and internal organelles are visible within the top cell)

RECOVERY TO

HEALTHY ACTIVE LIFE

THANK YOU

• journal club (22-10-09)
• topic autologus chondrocyte implantation
• THE ROLE OF AUTOLOGOUS CHONDROCYTE IMPLANTATION (ACI) IN THE TR
• Slide 4
• AUTOLOGOUS CHONDROCYTE GRAFTS MULTICENTRIC TRIAL WITH 28 KNEE
• Slide 6
• Slide 7
• Articular Cartilage
• Hyaline Cartilage Structure 1048715The ldquostuffrdquo of cartilage
• Slide 11
• Cartilage Injury Occurs in Many Forms
• Articular Cartilage Defects a treatment challenge
• AND WHAT IS IN OUR BASKET
• SO IT LED US TO SEARCH OF MORE PROMISING OPTION
• Autologous Chondrocyte Implantation (ACI) BACKGROUND
• Identifying a Carticelreg Patient
• Identifying a Carticelreg Patienthelliphellip
• Pre-requisite for surgery
• Autologous Chondrocyte Implantation (ACI)
• Techniques
• ACIMACI Generic Method
• Slide 23
• Treatment with CARTICEL
• CARTICEL Manufacturing and Delivery
• Step 2 Implantation
• CARTICEL Implantation
• Periosteal Patch
• Slide 29
• Slide 30
• Aci steps summarised
• Slide 32
• Complications
• Slide 34
• Slide 35
• FOLLOW UP Biopsy
• FOLLOW UP MRI
• FOLLOW UP ARTHROSCOPIC
• Rehabilitation guidelines
• ACI Rehabilitation
• ACI Rehabilitation (2)
• COMPARISON WITH OTHER METHODS OF TREATMENTS
• COMPARISON WITH OTHER METHODS OF TREATMENTShelliphelliphellip
• COMPARISON WITH OTHER METHODS OF TREATMENTShelliphelliphellip (2)
• CONCLUSIONS
• Slide 46
• Recent advancesHYAFF 3D matrix
• HYAFF-based Scaffold
• CHONDRONtrade
• RECOVERY TO
• Slide 51

bull Non woven felt 2 mm thick fiber diameter 10 micronsbull Chondrocytes are isolated and passaged in culture on plasticdishes up to 3 weeksbull Cells are seeded for 2 weeks on HYAFF scaffold at a density of1 x 106 cm2 resulting in a total of 4 x 106 cm2 seeded cells pergraft

HYAFF-BASED SCAFFOLD

CHONDRONtrade

Uses a cell ndash gel mixture (includes collagen hyaluronic acid and fibrin) that has fast gelling properties (1 ndash 5 min) upon transplantation

This cell and gel mixture enable even cell distribution three-dimensionally moldable to fit irregular defect shape and applicable to a larger defectThus there is minimal surgical exposure and reduced surgery time

(three-dimensional reconstruction of a chondron from the growth plate of the murine long bone the model was generated from multiple sections imaged in an electron microscope plasma membranes are coloured green and internal organelles are visible within the top cell)

RECOVERY TO

HEALTHY ACTIVE LIFE

THANK YOU

• journal club (22-10-09)
• topic autologus chondrocyte implantation
• THE ROLE OF AUTOLOGOUS CHONDROCYTE IMPLANTATION (ACI) IN THE TR
• Slide 4
• AUTOLOGOUS CHONDROCYTE GRAFTS MULTICENTRIC TRIAL WITH 28 KNEE
• Slide 6
• Slide 7
• Articular Cartilage
• Hyaline Cartilage Structure 1048715The ldquostuffrdquo of cartilage
• Slide 11
• Cartilage Injury Occurs in Many Forms
• Articular Cartilage Defects a treatment challenge
• AND WHAT IS IN OUR BASKET
• SO IT LED US TO SEARCH OF MORE PROMISING OPTION
• Autologous Chondrocyte Implantation (ACI) BACKGROUND
• Identifying a Carticelreg Patient
• Identifying a Carticelreg Patienthelliphellip
• Pre-requisite for surgery
• Autologous Chondrocyte Implantation (ACI)
• Techniques
• ACIMACI Generic Method
• Slide 23
• Treatment with CARTICEL
• CARTICEL Manufacturing and Delivery
• Step 2 Implantation
• CARTICEL Implantation
• Periosteal Patch
• Slide 29
• Slide 30
• Aci steps summarised
• Slide 32
• Complications
• Slide 34
• Slide 35
• FOLLOW UP Biopsy
• FOLLOW UP MRI
• FOLLOW UP ARTHROSCOPIC
• Rehabilitation guidelines
• ACI Rehabilitation
• ACI Rehabilitation (2)
• COMPARISON WITH OTHER METHODS OF TREATMENTS
• COMPARISON WITH OTHER METHODS OF TREATMENTShelliphelliphellip
• COMPARISON WITH OTHER METHODS OF TREATMENTShelliphelliphellip (2)
• CONCLUSIONS
• Slide 46
• Recent advancesHYAFF 3D matrix
• HYAFF-based Scaffold
• CHONDRONtrade
• RECOVERY TO
• Slide 51

CHONDRONtrade

Uses a cell ndash gel mixture (includes collagen hyaluronic acid and fibrin) that has fast gelling properties (1 ndash 5 min) upon transplantation

This cell and gel mixture enable even cell distribution three-dimensionally moldable to fit irregular defect shape and applicable to a larger defectThus there is minimal surgical exposure and reduced surgery time

(three-dimensional reconstruction of a chondron from the growth plate of the murine long bone the model was generated from multiple sections imaged in an electron microscope plasma membranes are coloured green and internal organelles are visible within the top cell)

RECOVERY TO

HEALTHY ACTIVE LIFE

THANK YOU

• journal club (22-10-09)
• topic autologus chondrocyte implantation
• THE ROLE OF AUTOLOGOUS CHONDROCYTE IMPLANTATION (ACI) IN THE TR
• Slide 4
• AUTOLOGOUS CHONDROCYTE GRAFTS MULTICENTRIC TRIAL WITH 28 KNEE
• Slide 6
• Slide 7
• Articular Cartilage
• Hyaline Cartilage Structure 1048715The ldquostuffrdquo of cartilage
• Slide 11
• Cartilage Injury Occurs in Many Forms
• Articular Cartilage Defects a treatment challenge
• AND WHAT IS IN OUR BASKET
• SO IT LED US TO SEARCH OF MORE PROMISING OPTION
• Autologous Chondrocyte Implantation (ACI) BACKGROUND
• Identifying a Carticelreg Patient
• Identifying a Carticelreg Patienthelliphellip
• Pre-requisite for surgery
• Autologous Chondrocyte Implantation (ACI)
• Techniques
• ACIMACI Generic Method
• Slide 23
• Treatment with CARTICEL
• CARTICEL Manufacturing and Delivery
• Step 2 Implantation
• CARTICEL Implantation
• Periosteal Patch
• Slide 29
• Slide 30
• Aci steps summarised
• Slide 32
• Complications
• Slide 34
• Slide 35
• FOLLOW UP Biopsy
• FOLLOW UP MRI
• FOLLOW UP ARTHROSCOPIC
• Rehabilitation guidelines
• ACI Rehabilitation
• ACI Rehabilitation (2)
• COMPARISON WITH OTHER METHODS OF TREATMENTS
• COMPARISON WITH OTHER METHODS OF TREATMENTShelliphelliphellip
• COMPARISON WITH OTHER METHODS OF TREATMENTShelliphelliphellip (2)
• CONCLUSIONS
• Slide 46
• Recent advancesHYAFF 3D matrix
• HYAFF-based Scaffold
• CHONDRONtrade
• RECOVERY TO
• Slide 51

RECOVERY TO

HEALTHY ACTIVE LIFE

THANK YOU

• journal club (22-10-09)
• topic autologus chondrocyte implantation
• THE ROLE OF AUTOLOGOUS CHONDROCYTE IMPLANTATION (ACI) IN THE TR
• Slide 4
• AUTOLOGOUS CHONDROCYTE GRAFTS MULTICENTRIC TRIAL WITH 28 KNEE
• Slide 6
• Slide 7
• Articular Cartilage
• Hyaline Cartilage Structure 1048715The ldquostuffrdquo of cartilage
• Slide 11
• Cartilage Injury Occurs in Many Forms
• Articular Cartilage Defects a treatment challenge
• AND WHAT IS IN OUR BASKET
• SO IT LED US TO SEARCH OF MORE PROMISING OPTION
• Autologous Chondrocyte Implantation (ACI) BACKGROUND
• Identifying a Carticelreg Patient
• Identifying a Carticelreg Patienthelliphellip
• Pre-requisite for surgery
• Autologous Chondrocyte Implantation (ACI)
• Techniques
• ACIMACI Generic Method
• Slide 23
• Treatment with CARTICEL
• CARTICEL Manufacturing and Delivery
• Step 2 Implantation
• CARTICEL Implantation
• Periosteal Patch
• Slide 29
• Slide 30
• Aci steps summarised
• Slide 32
• Complications
• Slide 34
• Slide 35
• FOLLOW UP Biopsy
• FOLLOW UP MRI
• FOLLOW UP ARTHROSCOPIC
• Rehabilitation guidelines
• ACI Rehabilitation
• ACI Rehabilitation (2)
• COMPARISON WITH OTHER METHODS OF TREATMENTS
• COMPARISON WITH OTHER METHODS OF TREATMENTShelliphelliphellip
• COMPARISON WITH OTHER METHODS OF TREATMENTShelliphelliphellip (2)
• CONCLUSIONS
• Slide 46
• Recent advancesHYAFF 3D matrix
• HYAFF-based Scaffold
• CHONDRONtrade
• RECOVERY TO
• Slide 51

THANK YOU

• journal club (22-10-09)
• topic autologus chondrocyte implantation
• THE ROLE OF AUTOLOGOUS CHONDROCYTE IMPLANTATION (ACI) IN THE TR
• Slide 4
• AUTOLOGOUS CHONDROCYTE GRAFTS MULTICENTRIC TRIAL WITH 28 KNEE
• Slide 6
• Slide 7
• Articular Cartilage
• Hyaline Cartilage Structure 1048715The ldquostuffrdquo of cartilage
• Slide 11
• Cartilage Injury Occurs in Many Forms
• Articular Cartilage Defects a treatment challenge
• AND WHAT IS IN OUR BASKET
• SO IT LED US TO SEARCH OF MORE PROMISING OPTION
• Autologous Chondrocyte Implantation (ACI) BACKGROUND
• Identifying a Carticelreg Patient
• Identifying a Carticelreg Patienthelliphellip
• Pre-requisite for surgery
• Autologous Chondrocyte Implantation (ACI)
• Techniques
• ACIMACI Generic Method
• Slide 23
• Treatment with CARTICEL
• CARTICEL Manufacturing and Delivery
• Step 2 Implantation
• CARTICEL Implantation
• Periosteal Patch
• Slide 29
• Slide 30
• Aci steps summarised
• Slide 32
• Complications
• Slide 34
• Slide 35
• FOLLOW UP Biopsy
• FOLLOW UP MRI
• FOLLOW UP ARTHROSCOPIC
• Rehabilitation guidelines
• ACI Rehabilitation
• ACI Rehabilitation (2)
• COMPARISON WITH OTHER METHODS OF TREATMENTS
• COMPARISON WITH OTHER METHODS OF TREATMENTShelliphelliphellip
• COMPARISON WITH OTHER METHODS OF TREATMENTShelliphelliphellip (2)
• CONCLUSIONS
• Slide 46
• Recent advancesHYAFF 3D matrix
• HYAFF-based Scaffold
• CHONDRONtrade
• RECOVERY TO
• Slide 51