23S.N. Redman et al. Review of Cartilage Repair StrategiesEuropean Cells and Materials Vol. 9. 2005 (pages 23-32) ISSN 1473-2262AbstractDefects of articular cartilage that do not penetrate to thesubchondral bone fail to heal spontaneously. Defects thatpenetrate to the subchondral bone elicit an intrinsic repairresponse that yields a fibrocartilaginous repair tissue whichis a poor substitute for hyaline articular cartilage. Manyarthroscopic repair strategies employed utilise this intrinsicrepair response to induce the formation of a repair tissuewithin the defect. The goal, however, is to produce a repairtissue that has the same functional and mechanicalproperties of hyaline articular cartilage. To this end,autologous osteochondral transfer can provide symptomaticrelief. This technique involves the excision of healthycartilage plugs from ‘non-load bearing’ regions of the jointfor implantation into the defect. Cell based transplantationmethods currently involve the transplantation of expandedautologous chondrocytes to the defects to form a repairtissue. This technique again involves the excision of healthycartilage from the joint for expansion. Current research isexploring the potential use of mesenchymal stem cells as asource for tissue engineering, as well as the combinationof cells with biodegradable scaffolds. Although currentrepair strategies improve joint function, further research isrequired to prevent future degeneration of repair tissue.Key words: Cartilage Repair, Articular Cartilage,Mesenchymal Stem Cells, Cartilage Defects, ChondrocytePlasticity.Address for correspondence:Prof. Charles Archer,Cardiff School of Biosciences,Museum Avenue,Cardiff,Wales, CF10 3USTel: +44(0)29 20875206Fax: +44(0)29 20874594E-mail: [email protected] cartilage has a poor intrinsic capacity for repair.There are two major problems that need to be addressedin repair of articular cartilage. The first is to fill the defectvoid with a tissue that has the same mechanical propertiesas articular cartilage. The second is to promote successfulintegration between the repair tissue and the nativearticular cartilage. Even a small defect caused bymechanical damage will fail to heal and degenerate overtime progressing to the debilitating condition ofosteoarthritis. This review will aim to discuss the intrinsicrepair response of articular cartilage, in the absence ofvascular and neural supply, and examine the procedurescurrently employed to promote articular cartilage repair.Cartilage DefectsPartial Thickness DefectsPartial thickness defects of articular cartilage resemblethe clefts and fissures observed during the initial stagesof osteoarthritis. Defects of this nature in mature tissuedo not heal spontaneously. This failure is thought to bedue to the fact that they do not penetrate to the subchondralbone and so, do not have access to the progenitor cells ofthe bone marrow space (Fig. 1A). It has been shown thatin a foetal lamb model, spontaneous repair of a superficialdefect does occur with no fibrous scar and restoration ofthe zonal organisation of articular cartilage (Namba etal., 1998). Whether this is true repair, or ‘void filling’ asgrowth occurs is open for debate. In mature tissue, alimited repair process does take place in response to thetrauma within the tissue immediately adjacent to the siteof the defect. The nature of this repair response has beeninvestigated and it has been observed that the cellsadjacent to the wound margins undergo cell death. Aftertwenty-four hours, however, there is an increase in cellproliferation or chondrocyte cluster formation.Concurrent with this proliferation is also an increase inmatrix synthesis and catabolism. This response is shortlived and there is failure to repair the defect (Mankin,1982). It has also been observed that cells can be inducedto migrate from the synovium across the articular surfaceto the lesion and under the influence of growth factorscan fill the defect with a repair tissue (Hunziker, 2001;Hunziker and Rosenberg, 1996). In the absence of a fibrinmatrix and mitogenic factors, these ‘synovial cells’ fail tofill the defect void due in part to the anti-adhesiveproperties of proteoglycans especially the small leucinerich proteoglycans such as biglycan, decorin andfibromodulin (Hunziker and Rosenberg, 1996). Thus, itCURRENT STRATEGIES FOR ARTICULAR CARTILAGE REPAIRRedman 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, UK24S.N. Redman et al. Review of Cartilage Repair Strategiesis not only the absence of access to the bone marrow cellsthat prevents the repair of partial thickness defects, thereare clearly other mechanisms involved that remain to befully elucidated.Full Thickness DefectsFull thickness defects pass through the zone of calcifiedcartilage and penetrate the subchondral bone therebygaining access to the cells that reside in the bone marrowspace including the mesenchymal stem cells located therein(Fig. 1B). The repair response elicited by this type of defectresults in the formation of a fibrocartilaginous tissue inthe defect void. The events leading up to the formation ofthe repair tissue in a rabbit model have been characterised(Shapiro et al., 1993), indicating an immediate responseto penetration of the subchondral bone in a full thicknessdefect with, in some cases, formation of hyaline-likearticular cartilage. This repair tissue is a poor substitutefor articular cartilage and, with time, there is markeddegeneration of the repair tissue and continueddegeneration of the native articular cartilage. It has beennoted (Shapiro et al., 1993) that during this process, thetissue adjacent to the wound margins becomes necroticand apart from occasional chondrocyte cluster formation,little to no remodelling occurs. It was also noted that theempty lacunae observed in the native tissue at the woundmargins were not filled by either native migratingchondrocytes or mesenchymal cells from the defect void.By light microscopy, continuity between the native andrepair tissue was observed but polarised light microscopyrevealed no true integration of the two matrices and alsorevealed frequent regions
View Full Document
Unlocking...