TISSUE ENGINEERING AND CARTILAGE REPAIR

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TISSUE ENGINEERING ANDCARTILAGE REPAIR
Rita Kandel MD CIHR-Bioengineering of Skeletal
Tissues Team Mt. Sinai Hospital, University of
Toronto Toronto, Canada
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• 46 million Americans have arthritis
• MMWR 200655(40)1089-1092.
• Increasing incidence of sports injuries

www.cartoonstock.com/lowres/iba0038l.jpg
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STANDARD TREATMENT

• Drugs Unsatisfactory
• 2) Joint replacement Unsatisfactory

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BIOLOGICAL APPROACH TO JOINT REPAIR

• Remodel and become part of the joint tissue

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ARTICULAR CARTILAGE TISSUE ENGINEERING
Scaffoldscells
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BIPHASIC CONSTRUCT FORMED IN VITRO
(OSTEOCHONDRAL-LIKE)
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SUBSTRATE (BONE SUBSTITUTE) FOR BIPHASIC
CONSTRUCT
Bone substitute
Calcium polyphosphate Fully Porous Strength
Biodegradable Biocompatible
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BIPHASIC CONSTRUCTAFTER 8 WEEKS OF CULTURE
CPP Bone substitute
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IMPLANTATION OF BIPHASIC CONSTRUCT
articular cartilage
BONE
subchondral bone
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IMPLANT IN PATELLAR GROOVE OF SHEEP KNEE AT 3
MONTHS
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HISTOLOGY OF BIPHASIC CONSTRUCTTHREE MONTHS
AFTER IMPLANTATIONIN A SHEEP JOINT
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NATIVE CARTILAGE-IMPLANT INTERFACE ZONE
NATIVE
Toluidine blue stain
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BONE INGROWTH AT 3 MONTHS
Backscatter Imaging
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CONTROL IMPLANTS IN SHEEP KNEE AT 3 MONTHS
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CONCLUSIONS

• 1) Biphasic constructs can repair focal
• defects in sheep joints.
• 2) May be suitable to form biological joint
  replacement

Bone Substitute Material CPP
In vitro-formed cartilage
2 mm
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CLINICAL RELEVANCE

• Arthritis prevalence1 in 7
• 128B arthritis associated health care costs in
  2003 (www.kaisernetwork.org)
• 652,000 joint replacements in 2003
• 40 increase in hip and 80 increase in knee
  replacements between 1997-2003
• CARTILAGE REPAIR

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CRITICAL ISSUES FOR CARTILAGE REPAIR

• Articular cartilage development
• Cell source
• To scaffold or not to scaffold?
• Re-creation of cartilage-bone interface
• Integration to adjacent tissues (bone and
  cartilage) and material degradation
• Physical properties of repair cartilage
• Survival of tissue in a hostile environment?
• Animal models to assess repair method

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CRITICAL ISSUES FOR CARTILAGE REPAIR

• Articular cartilage developmental biology

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CRITICAL ISSUES FOR CARTILAGE REPAIR

• Articular cartilage development
• Cell source

Embryonic stem cells Mesenchymal progenitor
cells Passaged articular chondrocytes
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CRITICAL ISSUES FOR CARTILAGE REPAIR

• Articular cartilage development
• Cell Source
• Is a scaffold required?
• Controversial
• Nanomaterials vs micromaterials
• Use may be dependant on type of lesion
  to be repaired (part of a toolbox)

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CRITICAL ISSUES FOR CARTILAGE REPAIR

• Articular cartilage development
• Cell source
• To scaffold or not to scaffold?
• Re-creation of cartilage-bone interface

Brehm W et al, Osteoarthritis and Cartilage, 2006
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CRITICAL ISSUES FOR CARTILAGE REPAIR

• Articular cartilage development
• Cell source
• To scaffold or not to scaffold?
• Re-creation of cartilage-bone interface
• Integration to adjacent tissues (bone and
  cartilage) and material degradation

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CARTILAGE REPAIR TISSUE INTEGRATION
Zhou G. et al Tissue Eng, 2006
Brehm W et al, Osteoarthritis and Cartilage, 2006
Brehm W et al, Osteoarthritis and Cartilage, 2006
Shao X et al, Tissue Engineering, 2006
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CRITICAL ISSUES FOR CARTILAGE REPAIR

• Articular cartilage development
• Cell source
• To scaffold or not to scaffold?
• Re-creation of cartilage-bone interface
• Integration to adjacent tissues
• What physical properties does repair cartilage
  require to survive after implantation?

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WEIGHT BEARING PROPERTIES OF CARTILAGE AFTER
IMPLANTATION
9 months E0.540.01MPa
3 months E 0.350.001 MPa
0 months E 0.020.004MPa
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CRITICAL ISSUES FOR CARTILAGE REPAIR

• Articular cartilage development
• Cell source
• To scaffold or not to scaffold?
• Re-creation of cartilage-bone interface
• Proper integration to adjacent tissues
• Physical properties of repair cartilage
• Survival of tissue in a hostile environment
  osteoarthritis (mechanical) or rheumatoid
  arthritis (inflammation)?
• Animal models to assess repair

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WHERE WILL WE BE IN 10 YEARS?

• Cell source identified
• Type of biomaterial
• Biological implants used clinically

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ACKNOWLEDGEMENTS

• Robert Pilliar Marc Grynpas Mark Hurtig
• Paul Zalzal Marcello Papini
• Lu Gan Jason Hong Caroline Spiteri
• Hanje Chen Jennifer Lee Stephen Waldman
• Nancy Valiquette Jian Wang Ardian Dudi
• Jean-Phillipe St-Pierre Amritha Decroos
  Tim Woodfield
• Jason Hong Katie Allan
• Funding CIHR, The Arthritis Society, NSERC,
  CAN