Michael M. Reinold, PT, ATCKevin E. Wilk, PTJeffrey R. Dugas, MDE. Lyle Cain, MDScott D. Gillogly, MD

REHABILITATION GUIDELINESAutologous Chondrocyte Implantation using Carticel

®

(autologous cultured chondrocytes)

• THE FOLLOWING HAS BEEN PROVIDED AS GENERALGUIDELINES FOR REHABILITATION FOLLOWING AUTOLOGOUSCULTURED CHONDROCYTE IMPLANTATION. INDIVIDUALRESULTS MAY VARY. THE EMPHASIS OF THIS GUIDELINE IS TOPROTECT THE GRAFT SITE AND RETURN THE PATIENT TO ANOPTIMAL LEVEL OF FUNCTION. NOTWITHSTANDING THEFOREGOING, THE INFORMATION PROVIDED IN THISDOCUMENT IS INTENDED FOR EDUCATIONAL PURPOSES. IT ISNOT A SUBSTITUTE FOR MEDICAL CARE NOR SHOULD IT BECONSTRUED AS MEDICAL ADVICE. CONSULTATION WITH THEPATIENT’S TREATING SURGEON OR ORTHOPEDIST ISRECOMMENDED PRIOR TO IMPLEMENTING A REHABILITATIONPROGRAM.

• PATIENT ADHERENCE TO THE PRESCRIBED REHABILITATIONPROGRAM IS IMPORTANT AND DEVIATION FROM THEPROGRAM MAY COMPROMISE CLINICAL BENEFIT FROMCARTICEL.

• LESION SIZE, LOCATION AND PATIENT AGE ARE SIGNIFICANTFACTORS IN DETERMINING A REHABILITATION PROGRAM FOREACH PATIENT.

• ALTHOUGH TIME FRAMES HAVE BEEN ESTABLISHED, IT IS MOREIMPORTANT THAT GOALS ARE REACHED AT THE END OF EACHPHASE PRIOR TO PROGRESSION TO THE NEXT.

• IT IS IMPORTANT TO AVOID EXCESSIVE LOADING/WEIGHTBEARING ON THE GRAFT SITE TO ENSURE PROPER HEALING.TAKE NOTE OF SPECIFIC PRECAUTIONS MENTIONED IN THEGUIDELINES. INFORMATION REGARDING THE LOCATION, SIZE,& SPECIFICS OF THE IMPLANTATION SITE SHOULD BEOBTAINED FROM THE SURGEON.

• PAIN AND SWELLING NEED TO BE CAREFULLY MONITOREDTHROUGHOUT THE REHABILITATION PROCESS. IF EITHEROCCUR, THE ENSUING ACTIVITY NEEDS TO BE IDENTIFIED ANDAPPROPRIATELY ADJUSTED TO LESSEN THE IRRITATION. ICEPACKS MAY BE USED TO CONTROL SWELLING. IGNORINGTHESE SYMPTOMS MAY COMPROMISE THE SUCCESS OF THESURGERY AND THE PATIENT’S OUTCOME.

• AT ANYTIME DURING THE REHABILITATION PROCESS OR AFTER,IF SHARP PAIN WITH LOCKING OR SWELLING IS EXPERIENCED,THE PATIENT SHOULD NOTIFY THEIR PHYSICIAN.

2

Indications

Carticel® is for autologous use and is indicated for the repair ofsymptomatic cartilage defects of the femoral condyle (medial, lateral ortrochlea), caused by acute or repetitive trauma, in patients who have hadan inadequate response to a prior arthroscopic or other surgical repairprocedure. Carticel is not indicated for the treatment of cartilage damageassociated with generalized osteoarthritis, and it is not recommended forpatients with total meniscectomy unless surgically reconstructed prior toor concurrent with Carticel implantation.

Important Safety Information

Any instability of the knee or malalignment of the joint should becorrected prior to or concurrent with Carticel implantation. It should notbe used in patients with a known history of allergy to gentamicin, otheraminoglycosides or materials of bovine origin. In addition, it should not beused in patients who have previously had cancer in the bones, cartilage, fator muscle of the treated limb. Use in children, patients over age 65, or injoints other than the knee has not yet been assessed.

The occurrence of a subsequent surgical procedure, primarily arthroscopy,following Carticel implantation is common. Symptoms leading toarthroscopic intervention have included catching, locking, clicking or pain;patients who develop these symptoms should be evaluated andarthroscopy may be indicated for treatment or further assessment. In post-marketing surveillance, the most frequent operative findings, in descendingorder of frequency, were graft overgrowth, arthrofibrosis, graft delamination(partial or complete), joint adhesions, meniscus lesion or tear,chondromalacia, loose body, and joint malalignment. Refer to packageinsert for full prescribing and safety information.

3

4

INTRODUCTION

Articular cartilage defects of the knee are a

common cause of pain and functional disability

in the orthopedics and sports medicine practice.

The avascular nature of articular cartilage

predisposes the individual to progressive

symptoms and degeneration due to the inability

of articular cartilage to heal. The following paper

will provide an overview of specific rehabilitation

guidelines and the basic principles of Carticel®

(autologous cultured chondrocytes) implantation

rehabilitation. These suggested programs are

designed using knowledge of basic science,

anatomy, and biomechanics of articular cartilage

as well as the natural course of healing following

implantation and are not intended as a substitute

for individual clinical judgement. The goal is to

restore optimal function in each patient as

quickly and safely as possible.

Specific Rehabilitation Guidelines 6-15CARTICEL IMPLANTATION 7-10Femoral Condyle Rehabilitation Guidelines

CARTICEL IMPLANTATION 11-14Trochlea Rehabilitation Guidelines

Rehabilitation Guideline Variations 16-19

Principles of Carticel Implantation Rehabilitation 20-25

References 26

CONTENTS

5

Specific Rehabilitation GUIDELINES

6

One of the most importantprinciples involved in Carticel®

(autologous culturedchondrocytes) implantationrehabilitation is programindividualization. Each patientwill have a unique response tothe surgical procedure and willtherefore progress throughrehabilitation at a different pace.Specific factors including lesionsize and location, tissue quality,age, lifestyle, and general healthwill affect the patient’spostoperative response.Therefore, these rehabilitationguidelines are designed toprovide a general framework forexercise progression that willhelp return the patient tofunctional activities in a safemanner. Some patients mayprogress more rapidly,advancing range of motion andweight bearing status in acontrolled fashion. Therehabilitation specialist shouldmonitor joint line pain, effusion,and symptomatic complaints todetermine if the patient isprogressing appropriately.However, the rehabilitationprogram should continue toavoid deleterious forces to thegraft site, including excessivecompressive and shear forces,during exercise progression.

Rehabilitation varies per person basedon age, weight, tissue quality,motivation, and activity level prior tosurgery. Target timeframes noted in eachphase are approximate and should beadjusted to the individual progress ofeach patient. Each person is different;rehabilitation progression is based on thesize, location, quantity, containment, andquality of the defect, as well as thehealing process after implantation.

The following section provides therehabilitation guidelines for isolatedfemoral condyle and trochlea lesions1.There are four distinct phases based onthe healing process following theimplantation of Carticel. Certain criteriamust be achieved prior to the patientprogressing to each phase of theprogram. Specific goals and criteria toprogress are listed under each phase.There is a great deal of variability frompatient to patient. When a patientachieves the goals of a particularrehabilitation phase, he or she may bemoved to the next phase at the surgeon’sdiscretion.

Exercises are progressed based on thepatient’s subjective reports of symptoms,and the clinical assessment of swellingand crepitation. If pain or swellingoccurs with any activities, they must bemodified to decrease symptoms, and theorthopedic surgeon should be contacted.

Please see the VARIATIONS section(pages 14-16) for a discussion ofrecommended alterations to the basicrehabilitation guidelines that addressconcomitant procedures.

GU

IDE

LINE

S

PHASE I - PROTECTION PHASE (WEEKS 0-6)

Goals:Protect healing tissue from load and shear forcesDecrease pain and effusion Restore full passive knee extensionGradually improve knee flexion Regain quadriceps control

Brace:Locked at 0˚ during weight-bearing activitiesSleep in locked brace for 2-4 weeks

Weight-Bearing:Non-weight-bearing for 1-2 weeks, may begin toe-touch weight bearing

immediately per physician instructionsToe touch weight-bearing (approx. 20-30 lbs) weeks 2-3Partial weight-bearing (approx. 1/4 body weight) at weeks 4-5

Range of Motion:Motion exercise 6-8 hours post-operativeFull passive knee extension immediatelyInitiate Continuous Passive Motion (CPM) day 1 for total of 8-12 hours/day

(0˚-40˚) for 2-3 weeksProgress CPM Range of Motion (ROM) as tolerated 5˚-10˚ per dayMay continue CPM for total of 6-8 hours per day for up to 6 weeks Patellar mobilization (4-6 times per day)Motion exercises throughout the dayPassive knee flexion ROM 2-3 times dailyKnee flexion ROM goal is 90˚ by 1-2 weeksKnee flexion ROM goal is 105˚ by 3-4 weeks and 120˚ by week 5-6Stretch hamstrings and calf

Strengthening Program:Ankle pump using rubber tubingQuad settingMulti-angle isometrics (co-contractions Q/H)Active knee extension 90˚-40˚ (no resistance)Straight leg raises (4 directions)Stationary bicycle when ROM allowsBiofeedback and electrical muscle stimulation, as neededIsometric leg press by week 4 (multi-angle)May begin use of pool for gait training and exercises by week 4

Functional Activities:Gradual return to daily activities If symptoms occur, reduce activities to Extended standing should be avoided reduce pain and inflammation

Swelling Control:Ice, elevation, compression, and edema modalities as needed

to decrease swelling

Criteria to Progress To Phase II:Full passive knee extension Knee flexion to 120˚Minimal pain and swelling Voluntary quadriceps activity

CARTICEL IMPLANTATIONFemoral Condyle Rehabilitation Guidelines

(Intended for small lesions (<5cm2) with no concomitant procedure; See “Rehabilitation Guideline Variations” section for others)

7

PHASE II - TRANSITION PHASE (WEEKS 6-12)

Goals:Gradually increase ROMGradually improve quadriceps strength/enduranceGradual increase in functional activities

Brace:Discontinue post-operative brace by week 6Consider unloading knee brace

Weight-Bearing:Progress weight-bearing as toleratedProgress to full weight-bearing by 8-9 weeksDiscontinue crutches by 8-9 weeks

Range of Motion:Gradual increase in ROMMaintain full passive knee extensionProgress knee flexion to 125˚-135˚Continue patellar mobilization and soft tissue mobilization, as neededContinue stretching program

Strengthening Exercises:Initiate weight shifts week 6Initiate mini-squats 0˚-45˚Closed kinetic chain exercises (leg press)Toe-calf raisesOpen kinetic chain knee extension progress 1 lb/weekStationary bicycle, low resistance (gradually increase time)Treadmill walking programBalance and proprioception drillsInitiate front and lateral step-upsContinue use of biofeedback and electrical muscle stimulation, as neededContinue use of pool for gait training and exercise

Functional Activities:As pain and swelling (symptoms) diminish, the patient may gradually increase functional activitiesGradually increase standing and walking

Criteria to Progress To Phase III:Full range of motionAcceptable strength level

• Hamstrings within 10%-20% of contralateral leg• Quadriceps within 20%-30% of contralateral leg

Balance testing within 30% of contralateral legAble to walk 1-2 miles or bike for 30 minutes

8

GU

IDE

LINE

S

PHASE III: MATURATION PHASE (WEEKS 12-26)

Goals:Improve muscular strength and enduranceIncrease functional activities

Range of Motion:Patient should exhibit 125˚-135˚ flexion

Exercise Program:Leg press (0˚-90˚)Bilateral squats (0˚-60˚)Unilateral step-ups progressing from 2" to 8"Forward lungesWalking programOpen kinetic chain knee extension (0˚-90˚)BicycleStair machineSwimmingSki machine/Elliptical trainer

Functional Activities:As patient improves, increase walking (distance, cadence, incline, etc.)

Maintenance Program:Initiate by weeks 16-20Bicycle – low resistance, increase timeProgressive walking programPool exercises for entire lower extremityStraight leg raisesLeg pressWall squatsHip abduction / adductionFront lungesStep-upsStretch quadriceps, hamstrings, calf

Criteria to Progress to Phase IV:Full non-painful ROMStrength within 80%-90% of contralateral extremityBalance and/or stability within 75% of contralateral extremityRehabilitation of functional activities causes no or minimal pain,

inflammation or swelling.

9

PHASE IV - FUNCTIONAL ACTIVITIES PHASE (WEEKS 26-52)

Goals:Gradual return to full unrestricted functional activities

Exercises:Continue maintenance program progression 3-4 times/weekProgress resistance as toleratedEmphasis on entire lower extremity strength and flexibilityProgress agility and balance drillsImpact loading program should be specialized to the patient’s demandsProgress sport programs depending on patient variables

Functional Activities:Patient may return to various sport activities as progression in rehabilitation andcartilage healing allows. Generally, low-impact sports such as swimming, skating,in-line skating, and cycling are permitted at about 6 months. Higher impactsports such as jogging, running, and aerobics may be performed at 8-9 monthsfor small lesions or 9-12 months for larger lesions. High impact sports such astennis, basketball, football, and baseball may be allowed at 12-18 months.

10

GU

IDE

LINE

S

PHASE I - PROTECTION PHASE (WEEKS 0-6)

Goals:Protect healing tissue from Restore full passive knee extension

load and shear forces Regain quadriceps controlDecrease pain and effusion Gradually improve knee flexion

Brace:Locked at 0˚ during ambulation and weight-bearing activitiesSleep in locked brace for 4 weeks

Weight Bearing:Immediate partial weight-bearing 25% body weight with brace locked in full extension, as tolerated 50% body weight by week 2 in brace

75% body weight by weeks 3-4 in brace

Range of Motion:Immediate motion exercise days 1-2Full passive knee extension immediatelyInitiate CPM on day 1 for total of 8-12 hours/day (0˚-60˚; if lesion > 6 cm2 0˚-40˚) for first 2-3 weeksProgress CPM ROM as tolerated 5˚-10˚ per dayMay continue use of CPM for total of 6-8 hours per day for 6 weeksPatellar mobilization (4-6 times per day)Motion exercises throughout the dayPassive knee flexion ROM 2-3 times dailyKnee flexion ROM goal is 90˚ by 2-3 weeksKnee flexion ROM goal is 105˚ by 3-4 weeks, and 120˚ by week 6Stretch hamstrings, calf

Strengthening Program:Ankle pump using rubber tubingQuad settingStraight leg raises (4 directions)Toe-calf raises by week 2Stationary bicycle when ROM allowsBiofeedback and electrical muscle stimulation, as neededIsometric leg press by week 4 (multi-angle)Initiate weight shifts by week 4May begin pool therapy for gait training and exercise by week 4

Functional Activities:Gradual return to daily activities If symptoms occur, reduce activities Extended standing should be avoided to reduce pain and inflammationUse caution with stair climbing

Swelling Control:Ice, elevation, compression, and edema modalities as needed

to decrease swelling

Criteria to Progress To Phase II:Full passive knee extension Knee flexion to 115˚–120˚Minimal pain and swelling Voluntary quadriceps activity 11

CARTICEL® (autologous cultured chondrocytes) IMPLANTATIONTrochlea Rehabilitation Guidelines

(Intended for small lesions (<5cm2) with no concomitant procedure; See “Rehabilitation Guideline Variations” section for others)

PHASE II - TRANSITION PHASE (WEEKS 6-12)

Goals:Gradually increase ROMGradually improve quadriceps strength/enduranceGradually increase functional activities

Brace:Discontinue brace by 6 weeks

Weight-Bearing:Progress weight-bearing as toleratedProgress to full weight-bearing by 6-8 weeksDiscontinue crutches by 6-8 weeks

Range of Motion:Gradually increase ROMMaintain full passive knee extensionProgress knee flexion to 120˚-125˚ by week 8Continue patellar mobilization and soft tissue mobilization, as neededContinue stretching program

Strengthening Exercises:Closed kinetic chain exercises (leg press 0˚-60˚) by week 8Initiate mini-squats 0˚-45˚ by week 8Toe-calf raisesOpen kinetic chain knee extension without resistanceBegin knee extension 0˚-30˚ then progress to deeper anglesStationary bicycle (gradually increase time)Stair machine at week 12Balance and proprioception drillsInitiate front and lateral step-upsContinue use of biofeedback and electrical muscle stimulation, as needed

Functional Activities:As pain and swelling (symptoms) diminish, the patient may gradually increase functional activitiesGradually increase standing and walking

Criteria to Progress To Phase III:Full range of motionAcceptable strength level

• Hamstrings within 10%-20% of contralateral leg• Quadriceps within 20%-30% of contralateral leg

Balance testing within 30% of contralateral legAble to walk 1-2 miles or bike for 30 minutes

12

GU

IDE

LINE

S

PHASE III: REMODELING PHASE (WEEKS 13-32)

Goals:Improve muscular strength and enduranceIncrease functional activities

Range of Motion:Patient should exhibit 125˚-135˚ flexion

Exercise Program:Leg press (0˚-60˚; progress to 0˚-90˚)Bilateral squats (0˚-60˚)Unilateral step-ups progressing from 2" to 6"Forward lungesWalking program on treadmillOpen kinetic chain knee extension (90˚-40˚) – progress 1 lb

every 10-14 days if no pain or crepitation – must monitor symptomsBicycleStair machineSwimmingSki machine/Elliptical trainer

Functional Activities:As patient improves, you may increase walking (distance, cadence, incline, etc.)Light running can be initiated toward end of phase based on

physician evaluation

Maintenance Program:Initiate by weeks 16-20Bicycle – low resistance, increase timeProgressive walking programPool exercises for entire lower extremityStraight leg raisesLeg pressWall squatsHip abduction / adductionFront lungesStep-upsStretch quadriceps, hamstrings, calf

Criteria to Progress to Phase IV:Full non-painful ROMStrength within 80%-90% of contralateral extremityBalance and/or stability within 75% of contralateral extremityRehabilitation of functional activities causes no or minimal pain,

inflammation or swelling.

13

PHASE IV - MATURATION PHASE (8-15 MONTHS)

Goals:Gradually return to full unrestricted functional activities

Exercises:Continue maintenance program progression 3-4 times/weekProgress resistance as toleratedEmphasize on entire lower extremity strength & flexibilityProgress agility and balance drillsProgress walking program as toleratedImpact loading program should be specialized to the patient’s demandsNo jumping or plyometric exercise until 12 monthsProgress sport programs depending on patient variables

Functional Activities:Patient may return to various sport activities as progression in rehabilitation andcartilage healing allows. Generally, low-impact sports such as swimming,skating, in-line skating, and cycling are permitted at about 6 months. Higherimpact sports such as jogging, running, and aerobics may be performed at 8-9months for small lesions or 9-12 months for larger lesions. High impact sportssuch as tennis, basketball, football, and baseball may be allowed at 12-18months.

14

GU

IDE

LINE

S

15

Rehabilitation Guideline VARIATIONS

16

Additional surgical procedures toaddress patellofemoral andtibiofemoral alignment,ligamentous laxity, and meniscalpathology are often performed at the time of the Carticel®

(autologous cultured chondrocytes)implantation to minimize possiblecontributing factors to graft failuredue to excessive compressive andshear forces. Rehabilitationprograms for Carticel may oftenrequire alterations based on theunique presentation of eachpatient. The next section willbriefly discuss variations to theisolated guidelines previouslydiscussed based on the extent oflesion damage and concomitantprocedures performed.

Anterior Cruciate LigamentReconstruction

Reconstruction of the anterior cruciateligament (ACL) using an ipsilateralpatellar tendon graft generally requires anincreased rate of passive ROM restoration.Harvesting the ipsilateral patellar tendonmay predispose the patient to thedevelopment of arthrofibrosis and loss ofmotion due to excessive scar tissueformation in the anterior aspect of theknee. Emphasis is placed on full passiveknee extension and patellar mobilizationsimmediately following surgery. PassiveROM is slightly accelerated for a femoralcondyle implantation during the initialphase of rehabilitation with the goals of90˚ of passive knee flexion by week 1,100˚-105˚ by week 2, 115˚ by week 4,125˚ by week 6, and 135˚ by week 8.Weight-bearing precautions and exerciseprogression are similar to the isolatedfemoral condyle guideline.

Lesions on the trochlea with aconcomitant ACL reconstruction require amore conservative approach than condylelesions. Passive ROM is progressed slowlyat first from 45˚ by day 3, to 60˚-75˚ byday 7, 90˚ by day 10, 100˚ by day 14,105˚ by week 3, 115˚ by week 4, and 125˚by week 6. Partial weight bearing istypically performed immediately in abrace locked in extension similar to anisolated trochlea lesion.

The use of a hamstring autogenous graftfor ACL reconstruction involves similarguidelines as the patellar tendon graft.However, caution should be taken withoveraggressive hamstring strengtheningin the early postoperative phases tominimize graft site morbidity.Aggressive strengthening of thehamstrings should typically be avoidedfor the first 6-8 weeks.

Allograft tissue may also be used forACL reconstruction. Rehabilitation doesnot differ significantly from anautogenous graft although the patientmay feel less anterior knee pain due tominimized graft morbidity.

Meniscal Allograft

Meniscal allograft transplantation altersthe rehabilitation program significantly toallow healing of the meniscuspostoperatively. While weight bearingguidelines are similar to that of theisolated femoral condyle guidelines,ROM and exercise progression is altered.The rate of passive ROM restoration isslightly decelerated to protect themeniscus with the goals of 60˚ of kneeflexion by week 1, 90˚ by week 2, 100˚by week 5, 110˚ week 6, 120˚ by week 7,and 125˚ by week 8. No active kneeflexion past 90˚ should be allowed forthe first 6-8 weeks to minimize strain onthe meniscus due to the close anatomical

VAR

IAT

ION

S

relationship of the hamstrings, capsulartissue, and meniscus. Furthermore,resisted hamstring strengthening istypically avoided until week 12. The useof bicycle and pool therapy usuallybegins by week 6-8.

Distal Realignment

A distal realignment, involving ananteromedialization of the tibial tubercle,is often performed during trochleaimplantations. Several aspects of therehabilitation program should be alteredto avoid excessive strain on the tibialtubercle. Passive ROM should beprogressed slowly with the goals of 45˚ byday 5, 60˚ by the end of week 1, 75˚ byweek 3, 90˚ by week 4, 115˚ by week 5,125˚ by week 6, and 125˚-135˚ by week8. Weight-bearing progression is similarto that of the isolated trochlea guidelineswith immediate partial weight bearingwith a knee brace locked in full extension.Scar tissue management and patellarmobilizations are recommended to beperformed to minimize the formation ofadhesions. Open kinetic chain kneeextensions can be initiated withoutresistance from 60˚-0˚ by weeks 6-8 astolerated. The use of a bicycle and pooltherapy can be initiated by weeks 6-8.

High Tibial Osteotomy

A high tibial osteotomy to realign thetibiofemoral joint generally requires aslightly accelerated passive ROMprogression to avoid motion losspostoperatively with the goals of 90˚ ofknee flexion by week 1, 105˚ by week 2,115˚ by week 3, 125˚ by week 4, and agradual progression past 125˚ beginningby week 6. Weight-bearing progression issimilar to that of the isolated femoralcondyle lesion, although weight-bearingmay be delayed based on radiographicevidence of bone formation, if bone

grafting is used, lesion size or location.Emphasis should be placed on restoringstrength and flexibility of the quadricepsfor optimal joint function. Furthermore,the use of external devices to alter theapplied load of the tibiofemoral joint maybe used such as orthotics, insoles, andheel wedges. The use of an osteoarthritisunloading brace is recommended whenthe postoperative knee brace isdischarged by weeks 6-8.

Lesion Size

The rehabilitation program may also varybased on the size of the lesion due to alarger area of articulation during weightbearing and exercises. The exact variationwill differ based on the location of thelesion, although a larger lesion is generallyconsidered to be 5 cm2 or greater.

Larger lesions on the femoral condyleswill generally necessitate a slower weight-bearing progression, particularly for themedial femoral condyle in the varus-aligned knee. Typically, weight-bearingprogression is delayed 2-4 weeks. Fullweight bearing without the use ofcrutches is progressed to by weeks 10-12,and may be longer for more complicatedlesions. The use of an unloader brace isrecommended to decrease compressiveforces to the graft site.

Conversely, large lesions on the trochleamay still progress with the same weight-bearing guidelines as smaller lesions.However, range of motion may be slightlydelayed to minimize shear forces at thepatellofemoral. Knee flexion passive rangeof motion should be progressed based ona patient’s report of pain or symptoms. Ingeneral, ROM is performed from 0˚-45˚during the first week, progressing to 75˚by week 2, 90˚ by week 3, 100˚-105˚ byweek 4, progressing to 120˚ by weeks 6-8.Open kinetic chain active knee extension

17

exercises should also be avoided for largetrochlea lesions until week 10 and arethen progressed slowly with lowresistance. Aggressive resisted kneeextension exercises should be avoided for9-12 months.

Uncontained Lesion

Large lesions are often uncontainedlesions. The presence of anuncontained lesion will alter the weight-bearing progression due to thecomplexity of the repair and thestability of the suture fixation. Therehabilitation program should be alteredsimilar to the guidelines for largecondyle or trochlea lesions. Therefore,for uncontained condyle lesions, theweight-bearing progression is typicallydelayed approximately 2-4 weeks, andfor uncontained trochlea lesions therange of motion and exercise programsare decelerated similar to large lesions.Heavy resisted open kinetic chainexercises should be avoided for at least3-6 months postoperatively on thefemur and 9-12 months on the trochlea.The rehabilitation progression will behighly individualized for these patientsbased on the physician’s discretion andthe size and containment of the lesion.

Osteochondritis Dissecans

The rehabilitation program for aCarticel® (autologous culturedchondrocytes) implantation procedure toaddress an osteochondritis dissecansdoes not vary considerably in terms ofimmediate postoperative weight bearing,range of motion, or exercises guidelines.However, when the patient beginsreturning to functional activities duringthe later phases of rehabilitation, aslower approach is typically utilized. Areturn to low impact activities is usuallydelayed for at least 6 months

postoperative. Emphasis should beplaced on a gradual program of walkingby 6-8 months, progressing to lightjogging and running by 8-9 months, andeventually jumping by 9-12 monthspostoperative at the earliest.

In the event that a bone graftingprocedure is needed concomitantly, thepatient should be non-weight bearing forapproximately 2-4 weeks, progressing tofull weight bearing by 12-16 weeks.

Multiple Lesions

The presence of multiple lesions will alterthe rehabilitation program based on thelocation of each lesion, and will typicallyinvolve a more conservative postoperativeprogram. For multiple lesions on thefemoral condyles or trochlea, therehabilitation program is adjusted similarto the guidelines for a large condylar ortrochlea lesion, respectively. However, thecombination of a lesion on the condyle aswell as the trochlea will vary significantly.The rehabilitation program should takeinto consideration the precautions of bothlesion sites. Therefore, the weight-bearingprogression would typically assume thepostoperative precautions similar to anisolated femoral condyle lesion to avoidoveraggressive compressive forces.Conversely, the range of motion andexercise progression would typicallyassume the postoperative precautionssimilar to a trochlea lesion to avoiddetrimental shear forces. Thus the patientshould be non-weight bearing for 2 weekspostoperative, progressing to 25% bodyweight by week 5, 50% body weight byweek 6, and gradually progressing to fullweight bearing by weeks 9-12 based onlesion specifics. Knee flexion range ofmotion should progress to 90˚ by week 3,105˚ by week 4, and 120˚ by week 6.Lesion size may further delay the range ofmotion and weight-bearing progression.18

VAR

IAT

ION

S

19

PRINCIPLES of Carticel® (autologous culturedchondrocytes) Implantation Rehabilitation

20

There are several key principlesinvolved when designingrehabilitation programs followingCarticel implantation. These keyprinciples include: creating ahealing environment, thebiomechanics of the knee,restoring soft tissue balance,reducing post-operative pain,restoring muscle function,gradually progressing appliedloads, and team communication.We briefly describe each one asthey relate to the rehabilitationprogram.

Create a Healing Environment

The first principle of Carticelrehabilitation involves creating anenvironment that facilitates the repairprocess while avoiding potentiallydeleterious forces to the graft site. Thisinvolves a thorough knowledge of thephysiological repair process followingimplantation. Through animal studies, aswell as the close monitoring of thematuration of the repair tissue in humanpatients via arthroscopic examination,four different biological phases ofmaturation have been identified.2-6

The first phase is the proliferation-protection phase, which usually involvesthe first six weeks following cellimplantation. During the first 24 hoursafter cell implantation, the cells line thebase of the lesion, proliferate and producea matrix that will fill the defect with a softrepair tissue up to the level of theperiosteal cover. Passive range of motionand controlled partial weight bearing willhelp promote cell function. During thisinitial phase, controlled active and passive

range of motion and a gradual weight-bearing progression are criticalcomponents to the rehabilitation process.

Controlled compression anddecompression forces observed duringweight bearing may provide the signals tothe chondrocytes to produce anappropriate matrix. A progression ofpartial weight bearing with crutches isused to gradually increase the amount ofload applied to the weight-bearingsurfaces of the joint. The use of a pool oraquatic therapy may be beneficial tobegin gait training and lower extremityexercises. The buoyancy of the waterdecreases the amount of weight-bearingforces to approximately 25% body weightwith a water depth to the axilla, and 50%with water depth to the waist.7 Thus apool may be used during early phases ofrehabilitation to perform limited weight-bearing activities.

Passive range of motion activities, such ascontinuous passive motion (CPM)machines, are also generally performed 6-8 hours after surgery to nourish thehealing articular cartilage and prevent theformation of adhesions. CPM usage istypically performed for at least 2-3 weeks,with recommended usage up to 6-8weeks. The CPM is recommended forapproximately 6-8 hours per day, whichmay be broken into 2-3 hour segments.Motion exercises may assist in creating asmooth, low frictional surface by slidingagainst the joint’s articular surface. Theuse of CPM has been shown to enhancecartilage healing and long-term outcomesfollowing articular cartilage procedures.8,9

The second phase is the transitional-protective phase, which typically includesweeks 7 through 12. The repair tissue atthis point is spongy and compressiblewith little resistance. Upon arthroscopic

PRIN

CIPLE

S

examination, the tissue may, in fact, havea wave-like motion to it when sliding aprobe over the tissue. During this phase,the patient usually progresses from partialweight bearing to full weight bearing.Continued maturation of the repair tissueis fostered through higher level functionaland motion exercises. It is during thisphase that patients typically resume mostnormal activities of daily living.

The third phase is known as theremodeling-functional phase, andtypically occurs from 12 weeks through32 weeks postoperatively. During thisphase there is usually a continuousproduction of matrix with furtherremodeling into a more organizedstructural tissue. The tissue at this pointhas the consistency of soft plastic uponprobing. As the tissue becomes more firmand integrated, it allows for morefunctional training activities to beperformed. At this point, the patienttypically notes improvement of symptomsand has generally normal motion.

The final phase is known as thematuration and optimization phase, andcan last up to 15 to 18 months post-implantation depending upon the sizeand location of the lesion. It is during thisphase that the repair tissue usuallyreaches its full maturation. The stiffness ofthe cartilage resembles that of thesurrounding tissue.5,6

Biomechanics of the Knee

The next rehabilitation principle involvesthe biomechanics of the tibiofemoral andpatellofemoral joint during normal jointarticulation.

Articulation between the femoral condyleand tibial plateaus is constant throughoutknee range of motion. The anterior

surface of the femoral condyles is inarticulation with the middle aspect of thetibial plateau near full knee extension. Asthe knee moves into greater degrees ofknee flexion, the femoral condylesprogressively roll and slide posteriorly,causing articulation to shift posteriorly onthe femoral condyle and tibial plateaus.10, 11

Articulation between the inferior marginof the patella and the trochlea begins atapproximately 10° – 20° of knee flexion.11

As the knee proceeds into greater degreesof knee flexion, the contact area of thepatellofemoral joint moves proximallyalong the patella. At 30°, the area ofpatellofemoral contact is approximately 2 cm2.11 The area of contact graduallyincreases as the knee is flexed. At 90° ofknee flexion, contact area increases up toapproximately 6 cm2.12

Using this knowledge of the jointkinematics, the rate of weight bearing andpassive range of motion may beprogressed based on the exact location ofthe lesion. For example, a lesion on theanterior aspect of the femoral condylemay be progressed into deeper degrees ofpassive knee flexion without causingarticulation at the graft site. Conversely,lesions on the posterior condyle mayrequire a slower rate of passive range ofmotion progression due to the progressiverolling and sliding component ofarticulation during deeper flexion.Furthermore, lesions on a non-weight-bearing surface, such as the trochlea, mayinclude immediate partial weight bearingwith a brace locked in full knee extensionwithout causing excessive compressionon the graft site. The use of apostoperative brace is recommended toassure that weight bearing is performed ina non-articulating range of motion.

21

Rehabilitation exercises can be alteredbased on the biomechanics of the knee toavoid excessive compressive or shearingforces. Open kinetic exercises, such asknee extension, are commonly performedfrom 90˚ – 40˚ of knee flexion. Thisrange of motion provides the lowestamount of patellofemoral joint reactionforces while exhibiting the greatestamount of patellofemoral contact area.11-13

Closed kinetic chain exercises, such as theleg press, vertical squats, lateral step-ups,and wall squats, are best performedinitially from 0˚ to 30˚ and thenprogressed to 0˚ to 60˚ where tibiofemoraland patellofemoral joint reaction forcesare lowered.11-13 As the graft site heals andpatient symptoms subside, the ranges ofmotion should be progressed to allowgreater muscle strengthening in largerranges. Exercises are progressed based onthe patient’s subjective reports ofsymptoms, and the clinical assessment ofswelling and crepitation. If pain orswelling occurs with any activities, theymust be modified to decrease symptoms,and the orthopedic surgeons should becontacted.

Restore Soft Tissue Balance

One of the more important aspects ofCarticel® (autologous culturedchondrocytes) rehabilitation involves theavoidance of arthrofibrosis. This isusually achieved by focusing on therestoration of full knee extension, patellamobility, and soft tissue flexibility of theknee and entire lower extremity. Theinability to fully extend the knee mayresult in abnormal joint kinematics andsubsequent increases in patellofemoraland tibiofemoral joint contact pressure,strain on the quadriceps muscle, andmuscular fatigue.15 Several authors havereported that immediate (post-operative

day 1) motion is essential to avoid rangeof motion complications and minimizepoor functional outcomes.16, 17 Therefore,a drop-lock post-operative knee bracelocked into 0˚ of extension is generallyused, and CPM and passive range ofmotion out of the brace are typicallyperformed 6-8 hours following surgery.

The goal is to achieve at least 0˚ of kneeextension the first few days post-operatively. Specific exercises utilizedmay include manual passive range ofmotion exercises performed by therehabilitation specialist, supine hamstringstretches with a wedge under the heel,and gastrocnemius stretching with atowel. Overpressure of 6-12 pounds maybe used for a low-load, long-durationstretch as needed to achieve fullextension.

Patients will often exhibit a certainamount of hyperextension preoperativelyor in the uninvolved knee. For patientswith significant hyperextension of theuninvolved extremity, regainingapproximately 5°-7° of hyperextensionthrough stretching techniques in theclinic is suggested. The remaininghyperextension may be achieved throughfunctional activities. We believe thisallows the patient to gain a greater degreeof neuromuscular control at the endrange of extension, and avoidsuncontrolled and unexpectedhyperextension movements.

The loss of patellar mobility followingCarticel implantation may be due tovarious reasons, including excessive scartissue adhesions along the medial andlateral gutters. The loss of patellarmobility may result in range of motioncomplications and difficulty recruitingquadriceps contraction. Patellarmobilizations in the medial-lateral and

22

PRIN

CIPLE

S

superior-inferior directions can beperformed by the rehabilitation specialistand independently by the patient duringtheir home exercise program.

Soft tissue flexibility and pliability are alsoimportant for the entire lower extremity.Soft tissue massage and scar managementcan be performed to prevent adhesiondevelopment around the anterior, medial,and lateral aspects of the knee. Inaddition, flexibility exercises can beperformed for the entire lower extremity,including the hamstrings, hip, and calfmusculature.

Post-operative adhesion formation mayresult in range of motion complications.The most beneficial treatment forarthrofibrosis is prevention. Earlyemphasis on extension and flexion rangeof motion, patella mobilizations, andcontinuous passive range of motion athome is important to help preventarthrofibrosis. It is essential that thepatient achieve full knee extensionimmediately following surgery. This maybe facilitated through the use of passiveextension range of motion, hamstringstretching, and gastrocnemius stretching.In the event that the patient developsflexion or extension range of motioncomplications, the rehabilitation specialistmay perform several therapeutictechniques. These can include moistheat, ultrasound to the anterior knee, scarand soft tissue mobilizations, patellarmobilizations, and passive range ofmotion and flexibility exercises. Low-load, long-duration stretches to achievefull knee extension may also beperformed in the supine position,incorporating a wedge underneath thepatients heel and concomitant weight(ranging from 5-12 pounds) applied tothe distal thigh, typically for 10-12minutes.

Although not common, it is possible foradhesions to form and attach to thehealing graft site. Therefore, cautionshould be used to avoid the developmentof arthrofibrosis. In the event that severeadhesions develop with loss of motion,the surgeon may perform an arthroscopiclysis of adhesions. Manual manipulationsare not commonly performed for Carticelpatients due to the possibility of adhesionformation to the graft site.

Furthermore, as the chondrocytes growand mature, graft hypertrophy may occurin a small number of patients, resulting insubjective reports of clicking and poppingat approximately 3 months post-operatively. This may be addressed bymodifying active and closed kinetic chainexercises to be performed with lighterresistance or in a symptom-free range ofmotion. Passive range of motion shouldcontinue to be performed to assist in theformation of a smooth articulation.

Emphasis of the rehabilitation program atthis point is to facilitate a smooth, low-friction articular surface through the useof controlled passive range of motion andcompressive loading (without sheer).Passive range of motion exercises shouldbe performed manually by therehabilitation specialist, as well asindependently by the patient periodicallythroughout the day. It is recommendedthat the patient perform passive range ofmotion 4-6 times per day. Furthermore,the use of low resistance bicycle ridingand aquatic therapy is recommended.

23

Reduction of Pain & Effusion

Numerous authors have studied theeffect of pain and joint effusion onmuscle inhibition. A progressivedecrease in quadriceps activity has beennoted as the knee exhibits increasedpain and distention.18, 19 Thus, thereduction in knee joint pain andswelling post-operatively is crucial torestore normal volitional quadricepsactivity. Treatment options for painand/or swelling may include analgesics,cryotherapy, high-voltage stimulation,ultrasound, and joint compression.

Restoring Muscle Function

The next principle involves restoringmuscle function of the lower extremity.Inhibition of the quadriceps muscle is acommon clinical enigma in the presenceof pain and effusion during the acutephases of rehabilitation immediatelyfollowing the implementation ofCarticel® (autologous culturedchondrocytes). Electrical musclestimulation and biofeedback are oftenincorporated with therapeutic exercisesto facilitate the active contraction of thequadriceps musculature. This appearsto facilitate the return of muscleactivation and may be valuable additionsto therapeutic exercises.20

Electrical stimulation may be used post-op day one while performing isometricand isotonic exercises such asquadriceps sets, straight leg raises, hipadduction and abduction, and kneeextensions. Electrical stimulation maybe used prior to biofeedback when thepatient presents acutely with theinability to activate the quadricepsmusculature. Once independent muscleactivation is present, biofeedback may beutilized to facilitate furtherneuromuscular activation of the

quadriceps. The patient mustconcentrate on neuromuscular control toindependently activate the quadricepsduring rehabilitation.

Exercises that strengthen the entirelower extremity, such as machineweights and closed kinetic chainexercises, should be included as thepatient progresses to more advancedphases of rehabilitation. It is importantthat total leg strength be emphasizedrather than concentrating solely on thequadriceps. Training of the hip, pelvis,core, and ankle located proximately anddistally along the kinetic chain should beemphasized to assist in controlling forceproduction and dissipation in the knee.In addition, the hip and ankle assist incontrolling abduction and adductionmoments at the knee joint.

Proprioceptive and neuromuscularcontrol drills of the lower extremitiesshould also be included to restoredynamic stabilization of the knee jointpostoperatively. Specific drills initiallycould include weight shifting side-to-side,weight shifting diagonally, mini-squats,and mini-squats on an unstable surfacesuch as a tilt board (usually during PhaseI of rehabilitation). Perturbations canfurther be added to challenge theneuromuscular system (usually duringPhase II of rehabilitation). Additionalexercises that may be performed includelateral lunges onto unstable surfaces andbalance beam walking (usually duringPhase III of rehabilitation).

Gradual Progression of Applied Loads

The next principle of Carticelrehabilitation involves graduallyincreasing the amount of stress appliedto the injured knee as the patientreturns to functional activities. The

24

PRIN

CIPLE

S

progression of weight-bearing and rangeof motion restoration, as previouslydiscussed, involves a gradualadvancement to assure thatcomplications such as excessive motionrestrictions or scar tissue formation areavoided while progressing steadily toavoid overstressing the healing graft site.An overaggressive approach early withinthe rehabilitation program may result inincreased pain, inflammation, oreffusion, as well as graft damage. Thissimple concept may be applied to theprogression of strengthening exercises,proprioception training, neuromuscularcontrol drills, and functional drills. Forexample, exercises such as weight shiftsand lunges can be progressed fromstraight plane anterior-posterior ormedial-lateral directions to involvemulti-plane and rotational movements.Exercises using two legs, such as legpress and balance activities, can beprogressed to single-leg exercises. Thus,the progression through the post-operative rehabilitation programinvolves a gradual progression ofapplied and functional stresses. Thisprogression is used to provide a healthystimulus for healing tissues whileassuring that forces are graduallyapplied without causing damage.

Additionally, Carticel patients maybenefit from use of orthotics, insoles,and bracing to alter the applied loads onthe articular cartilage during functionalactivities. These devices can be used toavoid excessive forces by unloading thearea of the knee where the implantationis located. Unloader braces are oftenused for patients with subtle uncorrectedabnormal alignments (genu varum) andlarge or uncontained lesions, as well asin the presence of concomitantosteotomies and meniscal allografts.

Team Communication

An important principle of Carticelimplantation rehabilitation involves ateam approach between the surgeon,physical therapist, and patient.Communication between the surgeonand therapist is essential to determine anaccurate rate of progression based on thelocation of the lesion, size of the lesion,tissue quality of the patient, and theaddition of concomitant surgicalprocedures. Also, communicationbetween the medical team and patient isessential to provide patient educationregarding the avoidance of deleteriousforces, as well as compliance withprecautions. Often, a preoperativephysical therapy evaluation may beuseful to mentally and physicallyprepare the patient for the Carticelprocedure and post-operativerehabilitation. Often times, the patientmay become pain free earlier thanexpected, potentially endangering theCarticel implantation. As a generalmatter, the clinician shouldcommunicate to the patient that,although they may experience minimalsymptoms, they should adhere strictly tothe rehabilitation guidelines.

25

REFERENCES

26

1. Gillogly SD, Voight M, Blackburn T: Treatment of articular cartilage defects of the knee withautologous chondrocyte implantation. J Orthop Sports Phys Ther 28(4):241-251, 1998.

2. Grande DA, Pitman MI, Peterson L, et al. The repair of experimentally produced defects inrabbit articular cartilage by autologous chondrocyte implantation. J Orthop Res 7:208-218,1989.

3. Brittberg M, Lindahl A, Nilsson A, et al. Treatment of deep cartilage defects in the knee withautologous chondrocyte transplantation. N Eng J Med 331:889-895, 1994.

4. Brittberg M, Nilsson A, Lindahl A, et al. Rabbit articular cartilage defects treated withautologous cultured chondrocytes. Clin Orthop 326:270-283, 1996.

5. Peterson L, Minas T, Brittberg M, et al. Two- to 9-year outcome after autologous chondrocytetransplantation of the knee. Clin Orthop 374:212-234, 2000.

6. Peterson L, Brittberg M, Kiviranta I, et al. Autologous chondrocyte transplantation:Biomechanics and long-term durability. Am J Sports Med 30:2-12, 2002.

7. Harrison RA, Hillman M, Bulstrode S. Loading of the limb when walking partially immersed.Phsyiotherapy 78:1992.

8. Salter RB. The biological concept of continuous passive motion of synovial joints: The first18 years of basic research and its clinical application. In Ewing JW (ed), Articular Cartilageand Knee Joint Function. Raven Press, New York, 1990

9. Rodrigo JJ, Steadman JR, Sillman JF, et al. Improvement of full-thickness chondral defecthealing in the human knee after debridement and microfracture using continuous passivemotion. Am J Knee Surg 7:109-116, 1994.

10. Iwaki H, Pinskerova V, Freeman MAR. Tibiofemoral movement 1: The shapes and relativemovements of the femur and tibia in the unloaded cadaver knee. J Bone Joint Surg82B:1189-1195, 2000.

11. Martelli S, Pinskerova V. The shapes of the tibial and femoral articular surfaces in relation totibiofemoral movement. J Bone Joint Surg 84B:607-613, 2002

12. Hungerford DS, Barry M. Biomechanics of the patellofemoral joint. Clin Orthop 144:9-15,1979.

13. Huberti HH, Hayes WC. Patellofemoral contact pressures. J Bone Joint Surg 66A:715-724,1984.

14. Steinkamp LA, Dillingham MF, Markel MD, et al. Biomechanical considerations inpatellofemoral joint rehabilitation. Am J Sports Med 21: 438-444, 1993.

15. Perry J, Antonelli D, Ford W. Analysis of knee-joint forces during flexed-knee stance. JBone Joint Surg 57:961-967, 1975.

16. Millett PJ, Wickiewicz TL, Warren RF. Motion loss after ligament injuries to the knee: Part I:Causes. Am J Sports Med 29:664-675, 2001.

17. Shelbourne KD, Wilckens JH, Mollabashy A, et al. Arthrofibrosis in acute anterior cruciateligament reconstruction. The effect of timing of reconstruction and rehabilitation. Am JSports Med 19:332-336, 1991.

18. Spencer JD, Hayes KC, Alexander I. Knee joint effusion and quadriceps reflex inhibition inman. Arch Phys Med Rehabil 65:171-177, 1984.

19. Young A, Stokes M, Shakespeare DT, Sherman KP. The effect of intra-articular bupivicaineon quadriceps inhibition after meniscectomy. Med Sci Sports Exerc 15:154, 1983.

20. Snyder-Macler L, Delitto A, Bailey SL, Stralka SW. Strength of the quadriceps femorismuscle and functional recovery after reconstruction of the anterior cruciate ligament. Aprospective, randomized clinical trial of electrical stimulation. J Bone Joint Surg Am77:1166-73, 1995.

This protocol has been established as a guideline only.Each patient must be assessed separately and the rehabilitation modified accordingly by thetreating medical professionals.

A division of Genzyme Corporation55 Cambridge Parkway, Cambridge, MA 02142

1-800-453-6948 www.genzymebiosurgery.com©2006 Genzyme Corporation

C-00013.A 05/2006