Repair of Articular Cartilage in Knee Joints

Transcription

1 Repair of Articular Cartilage in Knee Joints 1

2 Cartilage Hyaline Fibrocartilage Elastic 2

3 Anatomy of Articular (Hyaline) Cartilage Hyaline cartilage is the load bearing material of diarthrodial joints that possesses an extremely low coefficient of friction. Lacks both blood supply and innervation. 3

4 Composition of Cartilage The extracellular matrix is composed of a dense network of fine collagen (type II) fibrils enmeshed in a concentrated solution of proteoglycans. Water makes up ~75% of the wet weight of hyaline cartilage. 4

5 Three Structural Zones Superficial Tangential Zone (STZ) Middle Zone Deep Zone 5

6 6

7 Primary Forces Affecting Cartilage Tensile 7

8 Compressive 8

9 Shear 9

10 Mechanical Properties Viscoelasticity: property of materials that exhibit both viscous and elastic characteristics when undergoing deformation allowing the material to present time dependent strain Anisotropy: the property of being directionally dependent Tension Compression Nonlinearity: the variables cannot be written as a linear combination of independent components. Tissue can be thought of as being bimodular 10

11 Mechanical Properties (continued) Permeability: determines the flow of fluid through the material by an applied pressure gradient. Inhomogeneity: Biomechanical properties are not uniform throughout the material 11

12 Mechanical Properties (continued) Mechano-Electrochemical Response: refers to the properties affected by the chemical constituents of cartilage Lubrication: necessary for reduction of the friction coefficient and thusly aids in maintaining high wear resistance 12

13 Articular Cartilage Defects Focal Defects trauma (impact, repetitive shear/torsional forces) Complex Defects osteoarthritis primary (aging) secondary (genetics, obesity, injury) osteochondritis dissecans (OCD) 13

14 Articular Cartilage Defects Grades of Damage: Grade I: Superficial lesions Grade II: Lesions are <50% cartilage depth Grade III: Lesions are >50% cartilage depth but do not extend into subchondral bone Grade IV: Lesions extend into subchondral bone 14

15 Debridement (Abrasion Anthroplasty) Removal of unstable cartilage around affected region Some remodeling of joint surface Used in conjunction with other procedures 15

16 Bone Marrow Stimulating Techniques Procedures: Drilling Micro-fracture How they work: Piercing of the subchondral bone causing bleeding Release of pluripotent mesenchymal stem cells Growth of fibrocartilage 16

17 Drilling Holes approx. 2mm in diameter are drilled into the subchondral bone exposed by the lesion Drilling has widely been replaced in clinical practice by microfracture due to thermal necrosis Development has gone into specialized drill bits and irrigation to combat bone necrosis 17

18 Micro-Fracture Small fractures are made in the subchondral bone with sharp awl Micro-fracture has become the commonly accepted practice used to repair small lesions < 2.5 cm 2 18

19 Bone Marrow Stimulating Techniques Effectiveness: Relatively quick recovery time Relief of symptoms while cartilage is intact Forms firbrocartilage Functional decline of cartilage over time 19

20 Autologous Chondrocyte Implantation (ACI) Biopsy of articular cartilage tissue (chondrocytes) is taken via arthroscopy Cells are grown in vitro for 3-6 weeks Methods of culturing cells involve a wide variety of different factors and are currently under development original methods caused chondrocytes to lose their differentiated phenotype 20

21 Autologous Chondrocyte Implantation First Generation ACI (ACI-P) Debridement of defect area Peristoeal flap harvested from the proximal medial tibia is secured over defect area Cultured cells are injected underneath the flap Flap is sealed 21

22 Autologous Chondrocyte Implantation Second Generation ACI (ACI-C) Bilayer collagen membrane (Chondro-Gide) is used in place of periosteal flap prevents hypertrophy and donor site morbidity 22

23 Tissue Engineering Tissue Engineering provides the goal of developing an ideal method of treatment that will restore complete functionality of the joint. It seeks to repair or regenerate damaged or diseased tissues using combinations of scaffolds, cells, and environmental cues such as bioactive molecules and physical factors. 23

24 Design Considerations Geometry control Time dependent with elastic component Resists impact loading Resists permanent deformation and fracture under cyclic loading Resists wear under cyclic articulation Adheres to adjacent tissue 24

25 Successful Implantation Currently a lack of methods to test the in vivo mechanical properties of engineered cartilage. Success currently determined by comparison to the competing methods. 25

26 Scaffolds Function: promote cell proliferation and chondrogenesis models ECM provides structural support used in conjunction with Growth Factors 26

27 Scaffolds Natural Synthetic Fibrin, Alginate, Hyaluronan, Chitosan biocompatible Polyglycolic acid (PGA), Polylactic acid (PLA) Ease of production and better resistance over time 27

28 Signaling Molecules Hormones, cytokines, and growth factors that influence both the development of chondrocytes and mesenchymal stem cells Ability to promote cartilage repair has been indicated through studies conducted on different species and in vitro Used in conjunction with scaffolds to achieve desired 28

29 Signaling Molecules Transforming Growth Factors alpha and beta (TGF-a, TGF-b) Bone morphogenic proteins Insulin-like Growth Factor-1 (IGF-1) Fibroblast Growth Factor Insulin-like Growth Factor-1 (IGF-1) Hyaluronic Acid (HA) Transcription factors (SOX-D) 29

30 TGF-Beta In vitro: induces mesenchymal stem cells to chondrocytes, promotes cell proliferation, promotes protein synthesis, and suppresses matrix metalloproteinasis In vivo: applied to defects in rabbits within a scaffold causing notable improvement in histology In excess: can cause osteophytosis 30

31 Bone Morphogenic Protein Increase chondrogenic phenotype (collagen II, proteoglycan) Resistant to fibroblastic invasion Promotes ECM synthesis Osteophytosis and prevention of chondrocyte migration 31

32 Challenges with Growth Factors Viable techniques to promote in vivo success Timing of release Appropriate timing release of each growth factor to optimize chondrogenesis Overcoming short half-life of proteins and maintaining high concentration repeat local administration gene therapy (complimentary DNA) 32

33 Use of Mesenchymal Stem Cells 33

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35 Bone Marrow Derived Mesenchymal Stem Cells Compared to ACI better proliferation rate than chondrocytes Bone marrow biopsy is less invasive than knee arthroscopy (less donor site morbidity) 1 less general or regional anesthesia application is required; consequently the cost is less. Able to harvest a sufficient number of cells 35

36 Future Considerations ACI and BMSC Implantation hold great promise for future development of tissue engineered cartilage. The refinement of tissue-engineering techniques will include evaluation of different cellscaffold combinations, genetic manipulation of implanted cells and use of alternative biomaterials. Future research should be aimed at investigating and evaluating tissue-engineering approaches to cartilage repair in disease-compromised models to gain a better understanding of clinically feasible designs. 36

37 References 1) Van C. Mow and X. Edward Guo (2002) Mechano-Electrochemical Properties of Articular Cartilage: Their Inhomogenities and Anisotropies. Annual Reviews Biomedical Engineering: 4, ) Asheesh Bedi, Scott A. Rodeo, and Alice J. Sophia (2009) The Basic Science of Articular Cartilage: Structure, Composition, and Function. Sports Health: a Multidisciplinary Approach: 6, ) Ranieri Cancedda, Beatrice Dozin, Paolo Giannoni, Rodolfo Quarto (2003) Tissue Engineering and Cell Therapy of Cartilage and Bone. Matrix Biology. 22, ) Musculoskeletal Biomechanics Laboratory, Columbia Univeristy. index.html 5) Nejadnik H, Hui JH, Feng Choong EP, Tai BC, Lee EH (2010) Autologous Bone Marrow- Derived Mesenchymal Stem Cells versus Autologous Chondrocyte Implantation: An Observational Cohort Study. Am J Sports Med. 38: ) Falah H, Nierenberg G, Soudry M, Hayden M, Volpin G (2010)Treatment of Articular Cartliage Lesions of the Knee. Int Orthrop. 34:

38 References 7) Farshid Guilak, David L. Butler, Steven A. Goldstein, and David J. Mooney (2003) Functional Tissue Engineering. Springerverlag, New York. 8) Getgood, A., L. Fortier, and N. Rushton. "Articular Cartilage Tissue Engineering." TODAY'S RESEARCH TOMORROW'S PRACTICE 5th ser. 91.B (2009): Journal of Bone and Joint Surgery. British Editorial Society of Bone and Joint Surgery. Web. 9) Ochi, Mitsuo, Nobuo Adachi, Hiro Nobuto, Shinobu Yanada, Yohei Ito, and Muhammed Agung. "Articular Cartilage Repair Using Tissue Engineering." (2004): Wiley Online Library. International Society for Artificial Organs. Web. 10) Roberts, Sally, Iain W. McCall, Alan J. Darby, Janis Menage, Helena Evans, Paul E. Harrison, and James B. Richardson. "Autologous Chondrocyte Implantation for Cartilage Repair: Monitoring Its Success by Magnetic Resonance Imaging and Histology." (2002). Web. 11) "Chester Knee Clinic Knee Problems - Articular Cartilage Damage." Chester Knee Clinic Welcome. Web. 02 Oct < 12)Bartlett, W. "Autologous Chondrocyte Implantation at the Knee Using a Bilayer Collagen Membrane with Bone Graft: A PRELIMINARY REPORT." Journal of Bone and Joint Surgery - British Volume 87-B.3 (2005): Web. 13) Peterson, Lars, Haris S. Vasiliasis, Mats Brittberg, and Anders Lindahl. "Autologous Chondrocyte Implantation : A Long-term Follow-up." The American Journal of Sport Medicine (2010). Web. 38