Review of Cartilage Repair Strategies ISSN 1473 2262 S N Redman et al European Cells and Materials Vol 9 2005 pages 23 32 CURRENT STRATEGIES FOR ARTICULAR CARTILAGE REPAIR Redman S N Oldfield S F and Archer C W CITER Cardiff Institute of Tissue Engineering and Repair Cardiff School of Biosciences Museum Avenue Cardiff CF10 3US Wales UK Abstract Introduction Defects of articular cartilage that do not penetrate to the subchondral bone fail to heal spontaneously Defects that penetrate to the subchondral bone elicit an intrinsic repair response that yields a fibrocartilaginous repair tissue which is a poor substitute for hyaline articular cartilage Many arthroscopic repair strategies employed utilise this intrinsic repair response to induce the formation of a repair tissue within the defect The goal however is to produce a repair tissue that has the same functional and mechanical properties of hyaline articular cartilage To this end autologous osteochondral transfer can provide symptomatic relief This technique involves the excision of healthy cartilage plugs from non load bearing regions of the joint for implantation into the defect Cell based transplantation methods currently involve the transplantation of expanded autologous chondrocytes to the defects to form a repair tissue This technique again involves the excision of healthy cartilage from the joint for expansion Current research is exploring the potential use of mesenchymal stem cells as a source for tissue engineering as well as the combination of cells with biodegradable scaffolds Although current repair strategies improve joint function further research is required to prevent future degeneration of repair tissue Articular cartilage has a poor intrinsic capacity for repair There are two major problems that need to be addressed in repair of articular cartilage The first is to fill the defect void with a tissue that has the same mechanical properties as articular cartilage The second is to promote successful integration between the repair tissue and the native articular cartilage Even a small defect caused by mechanical damage will fail to heal and degenerate over time progressing to the debilitating condition of osteoarthritis This review will aim to discuss the intrinsic repair response of articular cartilage in the absence of vascular and neural supply and examine the procedures currently employed to promote articular cartilage repair Key words Cartilage Repair Articular Cartilage Mesenchymal Stem Cells Cartilage Defects Chondrocyte Plasticity Address for correspondence Prof Charles Archer Cardiff School of Biosciences Museum Avenue Cardiff Wales CF10 3US Tel 44 0 29 20875206 Fax 44 0 29 20874594 E mail archer cardiff ac uk 23 Cartilage Defects Partial Thickness Defects Partial thickness defects of articular cartilage resemble the clefts and fissures observed during the initial stages of osteoarthritis Defects of this nature in mature tissue do not heal spontaneously This failure is thought to be due to the fact that they do not penetrate to the subchondral bone and so do not have access to the progenitor cells of the bone marrow space Fig 1A It has been shown that in a foetal lamb model spontaneous repair of a superficial defect does occur with no fibrous scar and restoration of the zonal organisation of articular cartilage Namba et al 1998 Whether this is true repair or void filling as growth occurs is open for debate In mature tissue a limited repair process does take place in response to the trauma within the tissue immediately adjacent to the site of the defect The nature of this repair response has been investigated and it has been observed that the cells adjacent to the wound margins undergo cell death After twenty four hours however there is an increase in cell proliferation or chondrocyte cluster formation Concurrent with this proliferation is also an increase in matrix synthesis and catabolism This response is short lived and there is failure to repair the defect Mankin 1982 It has also been observed that cells can be induced to migrate from the synovium across the articular surface to the lesion and under the influence of growth factors can fill the defect with a repair tissue Hunziker 2001 Hunziker and Rosenberg 1996 In the absence of a fibrin matrix and mitogenic factors these synovial cells fail to fill the defect void due in part to the anti adhesive properties of proteoglycans especially the small leucine rich proteoglycans such as biglycan decorin and fibromodulin Hunziker and Rosenberg 1996 Thus it Review of Cartilage Repair Strategies S N Redman et al Figure 1 Diagram illustrating a partial thickness focal defect in articular cartilage A and a full thickness defect that penetrates to the subchondral bone B is not only the absence of access to the bone marrow cells that prevents the repair of partial thickness defects there are clearly other mechanisms involved that remain to be fully elucidated revealed frequent regions of discontinuity Although the outcome of the natural repair response to full thickness defects is poor many operative procedures to alleviate joint pain are based upon this mechanism of repair Full Thickness Defects Full thickness defects pass through the zone of calcified cartilage and penetrate the subchondral bone thereby gaining access to the cells that reside in the bone marrow space including the mesenchymal stem cells located therein Fig 1B The repair response elicited by this type of defect results in the formation of a fibrocartilaginous tissue in the defect void The events leading up to the formation of the repair tissue in a rabbit model have been characterised Shapiro et al 1993 indicating an immediate response to penetration of the subchondral bone in a full thickness defect with in some cases formation of hyaline like articular cartilage This repair tissue is a poor substitute for articular cartilage and with time there is marked degeneration of the repair tissue and continued degeneration of the native articular cartilage It has been noted Shapiro et al 1993 that during this process the tissue adjacent to the wound margins becomes necrotic and apart from occasional chondrocyte cluster formation little to no remodelling occurs It was also noted that the empty lacunae observed in the native tissue at the wound margins were not filled by either native migrating chondrocytes or mesenchymal cells from the defect void By light microscopy continuity between the native and repair
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