cartilage repair - mit opencourseware · 3 mo. hyaline cartilage (some articular cartilage),...

HST 535HST 535

CARTILAGE REPAIRCARTILAGE REPAIR

M. Spector, Ph.D.M. Spector, Ph.D.

Massachusetts Institute of TechnologyMassachusetts Institute of TechnologyHarvard Medical SchoolHarvard Medical School

Brigham and Women’s HospitalBrigham and Women’s HospitalVA Boston Healthcare SystemVA Boston Healthcare System

Harvard-MIT Division of Health Sciences and Technology HST.535: Principles and Practice of Tissue Engineering Instructor: Myron Spector

Figure by MIT OCW.Figure by MIT OCW.

Figure by MIT OCW.Figure by MIT OCW.

Figure by MIT OCW.Figure by MIT OCW.

Implantation of the matrix alone, or supplemented with growth factors or genes for the GFsStem cells from

bone marrow infiltrate the defect

Implantation of a cell-seeded matrix

Photo removed for copyright

reasons.

Diagram removed for copyright reasons.

Future Clinical Practice Implementing Tissue Engineering

Microfracture Figure by MIT OCW.Figure by MIT OCW.

ELEMENTS FOR TISSUEELEMENTS FOR TISSUE ENGINEERINGENGINEERING

Tissue Engineering Triad*Tissue Engineering Triad*•• CELLSCELLS•• MATRIX (INSOLUBLE REGULATOR)MATRIX (INSOLUBLE REGULATOR)

–– Porous, absorbable biomaterialsPorous, absorbable biomaterials•• SOLUBLE REGULATORSSOLUBLE REGULATORS

–– Cytokines (Growth Factors)Cytokines (Growth Factors)Environmental FactorsEnvironmental Factors•• Mechanical loadingMechanical loading

** Used individually or in combination, but probablyUsed individually or in combination, but probablyalways best with a matrix (always best with a matrix (i.ei.e., with a biomaterial)., with a biomaterial)

ARTICULAR CARTILAGEARTICULAR CARTILAGE

Limits to RegenerationLimits to Regeneration•• Avascular (andAvascular (and aneuralaneural))•• Relatively low cell densityRelatively low cell density•• Cells of low mitotic activityCells of low mitotic activity•• Cells cannot freely migrateCells cannot freely migrate

Image removed for copyright reasons.

TISSUE ENGINEERINGTISSUE ENGINEERING

CellsCells•• Autologous, allogeneic, orAutologous, allogeneic, or xenogeneicxenogeneic•• Differentiated cell of the same tissueDifferentiated cell of the same tissue

type or another tissue type, or stem celltype or another tissue type, or stem cell

Autologous Chondrocyte Implantation

M Brittberg, et al., NEJM 33:889 (1994)

This process has been commercialized by Genzyme (for USD$11,500).

Diagram removed for copyright reasons.

UntreatedUntreateddefectsdefects

CellsCellsharvestedharvested

CellsCellsisolated isolated **

Cells suspended Cells suspended **

Periosteum harvestPeriosteum harvestsitesite

Cells cultured Cells cultured **

Cells injectedCells injectedunder periosteumunder periosteum

* by Genzyme * by Genzyme BiosurgeryBiosurgery

Canine StudyCanine StudyAutologous Chondrocyte ImplantationAutologous Chondrocyte Implantation

AUTOLOGOUS CHONDROCYTEAUTOLOGOUS CHONDROCYTE­-SEEDED COLLAGEN MATRIXSEEDED COLLAGEN MATRIX

4 mm4 mm

ChondrocyteChondrocyte--seededseededtype II collagentype II collagen implant*implant*

* Cells seeded into the matrix* Cells seeded into the matrix 24 hours24 hours**andand 4 weeks4 weeks prior to implantationprior to implantation

* HA Breinan,* HA Breinan, et alet al. J . Orthop. Res. 2000;18:781. J . Orthop. Res. 2000;18:781--789789and C.R. Lee,and C.R. Lee, et alet al. J. Orthop. Res. 2003;21:272. J. Orthop. Res. 2003;21:272--281281

Seeding of Collagen Matrices with CAC

Diagram removed for copyright reasons.

Collagen discs 9 mm diam x 3 mm thick

CR Lee, et al, Biomat. 2001;22:3145.

Chondral defect immediately postoperative. Arrow shows perforation of calcified cartilage and subchondral bone (SCB)

Defects treated by autologous chondrocyte implantation, 6 months postoperative

H. Breinan, et al. J. Orthop. Res. 2001;19:282-292

Photo removed for copyright

Photo removed for copyright

reasons.

reasons.

12 mo. Degraded tissue

6 mo. Art. cart. and fibrocartilage

H. Breinan, et al. JOR 2001;19:282

1.5 mo. Fibrous tissue

3 mo. Hyaline cartilage (some articular cartilage), fibrocartilage, and fibrous tissue

Tissue that formed after 3 and 6 months did not function longer term. Is the problem a lack of fill or the tissue types comprising the material?

AUTOLOGOUS CHONDROCYTE IMPLANTATION

Photo removed for copyright

Photo removed for copyright

reasons.

reasons.

Summary of Results: Canine Model

100%

90%

80%

70%

60%

50%

40%

30%

20%

10%

0%Untreated CAC CAC/ CAC/Control Alone Collagen II Collagen II

24 hr 4 wk

15 Wks Post-op, Mean, n=6

% O

rigi

nal D

efec

t Are

a Cultured Autologous

Chondrocytes Hyaline Fibrocartilage Fibrous

HA Breinan, et al. J . Orthop. Res. 2000;18:781-789and C.R. Lee, et al. J. Orthop. Res. 2003;21:272-281

Implantation of the matrix alone, (or supplemented with growth factors or genes for the GFs)

“Microfracture”: Stem cells from bone marrow infiltrate the defect

Implantation of a cell-seeded matrix

Photo removed for copyright

reasons.

Diagram removed for copyright reasons.

Figure by MIT OCW.Figure by MIT OCW.

Future Clinical Practice Implementing Tissue Engineering

CANINE MICROFRACTURE STUDYCANINE MICROFRACTURE STUDYTREATMENT GROUPSTREATMENT GROUPS

4 mm4 mm

Collagen (II)Collagen (II) filmfilm

MicrofractureMicrofracture

MicrofractureMicrofracture++

CollagenCollagenImplantImplant

ACACBoneBone

Collagen (II)Collagen (II) spongesponge

* HA Breinan,* HA Breinan, et alet al. J . Orthop. Res. 2000;18:781. J . Orthop. Res. 2000;18:781--789789

Hyaline Summary of Results: Canine Model Fibrocartilage

15 Wks Post-op, Mean, n=6

0%

10%

20%

30%

40%

50%

60%

70%

80%

90%

100%

Untreated Control

CAC Alone

CAC/Collagen II

24 hr

CAC/Collagen II

4 wk

% O

rigi

nal D

efec

t Are

a

Fibrous Cultured Autologous Chondrocytes

µfxAlone

µfx/Collagen II

Microfracture

Procedures currently used

• One scaffold for both cartilage and bone or two different scaffolds?

• Separate layer for calcified cartilage? • Scaffold(s) alone or cell-seeded? • One cell type for both cartilage and bone?

• Two cell types? –Seeded as a mixture? –

Articular Cartilage

Approaches for osteochondral defects? Diagrams removed for

Separate cell types in each scaffold?

copyright reasons.