DSM Biomedical

Materials that belong to the bodyMaterials that belong to the body

i-Polymers for i-ArthroplastyNew Polymer Technologies for Hip Arthroplasty

Leo SmitBusiness Director Implant Solutions

DSM Biomedical

DSM Biomedical

A story about bones, needing assistance…….

• Osteoarthritis (degenerative jointdisease)

• A group of diseases leading todegeneration of joints (bones andcartilage)

• Leading to pain, stiffness, cracking ofjoints, inflammation

• Some US #’s:• App 27 million US citizens are affected• Accounts for 25% of all visits to

primary care physiscians• 80% of people @ 65 yrs will show

radiographic evidence; 60% will showsymptoms

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Recurrence AdvancedDisease

Wellness At Risk CriticalEpisode

Interventions at all stages of the disease continuum

DSM NutritionalProducts

Disease continuum

Popu

latio

n Si

ze

DSM Biomedical

Total JointsEarly Interventional

DSM Biomedical

DSM approaches to joint health

i-flex – a joint health food supplement from DSM Nutritional Products, containingvitamins, carotenoids and galactolipids mixture that has been demonstrated in vitro tohave protective and even regenerative effects on human cartilage.

DSM is the world’s leading producer of Vitamin EEasy-XL – a novel family of UHMwPE grades with a

new molecular architecture to

increase crosslinking efficiencyHALS-UH – an Alternative Stabilizer that provides for

stabilization of UHMwPE powder

Bionate® Poly Carbonate Urethane polymers for soft bearing applications and

Early Interventional Arthroplasty.

DSM Biomedical

One of the largest successes of the medical profession

>2 Million Hip and Knee replacements carried out annually

Multitude of innovations, total hip/knee, uni-knee, hip resurfacing

Many materials being used – polymers, metals, ceramics

The Final Solution: Total Hip Arthroplasty

DSM Biomedical

Total Hip Replacement

DSM Biomedical

WEAR : the central theme in Hip Arthroplasty

Teflon too soft UHMwPE“Hit by friendly fire” : Macrophage attacks on PE wear particles cause

human biological/physiological responses leading to osteolysis.

Current artificial hip lifetimes are app 10 – 15 yearscurrent demographics ask for more!

Picture from Gomez-Barena

DSM Biomedical

Demographics make things worse

People are reachingPeople are reachinghigher ageshigher ages,,

which is good, yetwhich is good, yet

people arepeople are more obesemore obese and/orand/orour lifestyle is aimed at stayingour lifestyle is aimed at staying

more activemore active

so the pressure on our joints increasesso the pressure on our joints increases

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Alternative material approaches…….

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Materials options compared

Pros

- Longest clinical history

- Low wear when XL’d

- Excellent biocompatibility

- Highest clinical usage

Cons

- Oxidative susceptibility

- Processing steps

Pros

- Low wear

- Large head sizes

Cons

- Metal ion release

- Implant noise

- High cost of fabrication

Pros

- Low wear

- Excellent biocompatibility

Cons

- Fracture is clinical disaster

- High material cost

- Implant noise

MoM CoCUHMwPE

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Crosslinking – THE breakthrough in UHMwPE

Powder

ConsolidationM

achiningCleaning

Thermal treatm

ent

Crosslinking

PackagingSterilization

Implant

Stryker: Crossfire®X3TM

Zimmer: LongevityTM

ProlongTM

DePuy: MARATHONBiomet: ArCom® XLTS&N: XLPE

Stryker: Crossfire®X3TM

Zimmer: LongevityTM

ProlongTM

DePuy: MARATHONBiomet: ArCom® XLTS&N: XLPE

Picture: Zimmer

DSM Biomedical

Laboratory and clinical results

0.00

0.25

0.50

0.75

1.00

0 20 40 60 80 100Radiation Dose (kGy)

Nor

mal

ized

Wea

r

Longevity (Ref. 12)Conventional (Ref. 12)Durasul (Ref. 12)Conventional (Ref. 12)Marathon (Ref. 12)Crossfire (Ref. 13)Duration (Ref. 11)Gamma-air (Ref 14)Eto (Ref 15)N2 Vac - LabArcom - LabDuration - Lab"Marathon" - Lab"Durasul" - LabCrossfire - Lab"Longevity" - LabX3 - Lab

Edge-Loading Wear of Metal-on-Metal and Metal-on-X3® Highly CrosslinkedPolyethylene: Survival of the Fittest

Aiguo Wang, Ph.D., VP, Reconstructive Technologies, Stryker Orthopaedics, Mahwah,New Jersey, USA.

Both in-vitro as well as in-vivo wear

reduced as function of the Radiation Dose

Significant reduction in wear rate

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Radicals form new challenge

Macro-radicals are createdduring irradiation

Macro-radicals react with oxygen -

causing oxidative degradation of thebearing material

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RemeltingRemelting OROR AnnealingAnnealing

Additional stepAdditional step -- time consuming, coststime consuming, costs

Loss of mechanical propertiesLoss of mechanical properties

DiffusionDiffusion into the final Implant ORinto the final Implant OR PrePre--blendingblending with the polymerwith the polymer

Pre blended Vitamin EPre blended Vitamin E interferesinterferes with crosslinking process *with crosslinking process *

Vitamin E isVitamin E is consumedconsumed in the crosslinking processin the crosslinking process

Material turnsMaterial turns yellowyellow

Current radical removal optionsTh

erm

al tr

eatm

ent

Vita

min

E s

tabi

lizat

ion

Vita

min

E s

tabi

lizat

ion

* (Oral, E et al, Biomaterials (2005), 26(33), 6657* (Oral, E et al, Biomaterials (2005), 26(33), 6657--6663)6663)

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UHMwPE Paradigm

Ideally:

• wear resistance

• oxidation resistance

• mechanical properties

REAL WORLD so far notideal – Wear optimizationcauses compromises

Gomez-Barrena, E et al. Acta Orthopaedica 2008, 79 (6), 832.

OXIDATIVESTABILITY

WEARRESISTANCE

MECHANICALPROPERTIES

Reduced wear debris Reduced osteolysis

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Alternative stabilizer : HALS

HALS : Hindered Amine Light Stabilizer

No radical scavenging during radiation

no interference with the crosslinking process

Regenerative - Less stabilizer needed

No yellowing (consistent color) because no degradationcomponents are formed

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HALS : Crosslinking improvement

Higher crosslinkdensity for HALSthan for Vitamin Estabilized UHMwPE

• Tested 0.05 and 0.15 wt.% Vitamin Eversus 0.05 and 0.15 wt.% HALS

• No significant differences between0.05 and 0.15 wt.% HALS

• No influence type of HALS

Vitamin E: higher swellratio =lower XL density

2.0

2.5

3.0

3.5

4.0

4.5

5.0

5.5

6.0

6.5

7.0

0 20 40 60 80 100 120 140 160Irradiation dosage (kGy)

Swel

l rat

io (%

)

Reference 500 ppm Vit E1500 ppm Vit E 500 ppm HALS-1 1500 ppm HALS-1

GUR 1020 UHMwPE

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HALS-UH shows effective stabilization

Change in Carbonyl Index as a result of ageing during 6 weeks at room

temperature shows better stabilization compared to vitamin E

GUR 1020

-0.05

0

0.05

0.1

0.15

0.2

0.25

0.3

0.35

0 20 40 60 80 100 120 140 160

Irradiation dose (kGy)

Del

ta C

arbo

nyl I

ndex

Reference500 ppm Vit E1500 ppm Vit E500 ppm HALS-11500 ppm HALS-1

(FTIR: Abs 1718 cm-1/ 2020 cm-1)

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Hypothesis :

Incorporation of diene in UHMWPE will leave a pendant

unsaturation which is believed to make

crosslinking more efficient.

This enables the use of lower radiation doses, so

less radicals stay behind which may potentially

reduce oxidative degradation.

Further by adapting molecular architecture we

can optimize mechanical properties

Easy-XL™ : better crosslinkable UHMwPE

Growing polymer chain

M +

Incorporate dienes ingrowing PE chain:

+

Diene

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Wear Factor versus irradation dosage

0.0

0.5

1.0

1.5

2.0

2.5

3.0

3.5

4.0

4.5

0 20 40 60 80

Irradiation dosage (kGy)

Wea

r fac

tor (

10-6

mm

3/N

m)

ConventionalUHMwPE(GUR1020, 1050and MG003)

DSM Nextgeneration

- 50 kGy

- 2 (10-6 mm3/N m)

Easy-XL™ needs significantly less radiation for low wear

Results show that 25 kGy irradiation (i.e. sterilization dose) resulted in a

wear resistance comparable to highly XL materials

Pin on Disk wear measurements.See Eva Wisse et.al. 4th International UHMWPE Meeting, Turin, 2009

DSM Biomedical

Less remaining free radicals with Easy-XL™

For both conventional UH and Easy-XL™ it was shown that 75 kGy radiationleaves behind 2-3 times higher radical content than 25 kGy

Easy-XL™ crosslinked material has much less residualradicals!

325 330 335 340 345 350

M325KGY1 M375KGY1

EPR

inte

nsity

[arb

.uni

ts]

Magnetic Field [mT]325 330 335 340 345 350

S2825KGY1 S2875KGY1

EPR

inte

nsity

[arb

.uni

ts]

Magnetic Field [mT]

25 kGy75 kGy

VNB, 12 C=C/100K C MG003 25 kGy75 kGy

electron spin resonance (ESR) spectroscopy

DSM Biomedical

0

5

10

15

20

25

30

0 5 10 15 20

Strain [%]

Stre

ss [M

Pa]

3736 - 0kGyGUR 1020-0 kGy

Better Mechanical Properties

Optimizing theMolecular Architecture

enables us to find a

new balance inmechanical properties.

Easy-XL™ is a stronger material:- a.o. 30% higher Yield Stress

DSM Biomedical

Conclusion – will we break the paradigm?

HALS-UH and Easy-XL™,

separate or combined,form a strong vehicle to

break the paradigm,

creating novel polyethylenes for arthroplasty,having

better wear resistance,better mechanical properties

andbetter oxidative stability

all at the same time.

OXIDATIVESTABILITY

WEARRESISTANCE

MECHANICALPROPERTIES

Reduced wear debris Reduced osteolysis

DSM Biomedical

Yet…….……….

ALL innovations thus far have been aimed atincreasing the hardness

of the bearing material

This is opposite of what is present in the human body:Cartilage is much lower in hardness than polyethylene

DSM Biomedical

Arthroplasty – real cartilage

DSM Biomedical

Arthroplasty – real cartilage

Spongy and Lubricated…..

DSM Biomedical

Hypothesis

Increased Compliance (compressibility) andLubrication can lead to breakthrough technology

A Bio-mimicking Material

PolyCarbonate UrethanesBionate® PCU

DSM Biomedical

First Compliant Total Hip Implant

www.activeimplants.com

DSM Biomedical

Imitating Joints vs Replacing Joints

Graph compiled b y Active Implants; IMUKA 2010 PolyCarbonate Urethane, A compliant soft bearing material in THA, Emanuele NoccoArticular cartilage data from middle depth values of human distal femur in Adult Articular Cartilage by MHR Freeman,1974;UHMWPE Data from Steve Kurtz, PhD, Exponent, Inc.PU Data from DSM PTG SR = Strain Rate

PU(Bionate 80A)

Cartilage in M/L DirectionUHMWPE

Cartilage in A/P Direction(Parallel)

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Contact Angle

Average Std. Dev.

Bionate® 80A PCU 76.5 0.5UHMWPE 104 2.6

PCU Material MoreHydrophilic

All done with distilled water.All done with distilled water.

DSM Biomedical

The effect: Hydroplaning

The lower contact anglehelps to establish a

full fluid film

between the bearingsurfaces, enabling

them to

“hydroplane”

with very low level offriction.

www.activeimplants.com

DSM Biomedical

Enabling Technology for Early Intervention

The “body-like” characteristics of PCU’s also make them very likelycandidates for earlier interventions: e.g. direct use against Cartilage

www.activeimplants.com

DSM Biomedical

Acknowledgements

In 2007 DSM Biomedical initiated a new R&D program to developnew polyethylene materials for use in Arthroplasty.

Our Team:

Eva WisseNilesh Kukalyekar

Jan StolkRob Janssen

Tim KiddMicha Mulders

Harold SmeltPieter Gijsman

Bill FullerMarc Hendriks

DSM Biomedical

Materials that belong to the bodyMaterials that belong to the body

THANK YOU

DSM Biomedical

The description by DSM Biomedical of the characteristics and properties of its products as contained in this presentation issupported by research and believed to be reliable. It is for general information purposes only, and may not be relied uponin individual situations. Products are supplied under contract containing detailed product specifications, and the user shallbe exclusively responsible to assess the suitability of the product as specified for any individual application or use.