Articular cartilage repair

Partial-thickness articular cartilage defects, analogous to the clefts and fissures that characterize the early stages of human osteoarthritis, do not heal. It was the aim of our study to identify the innate limitations of this biological system, which are operative in impeding regeneration, and to establish a treatment protocol by means of which the intrinsic tissue repair potential may be triggered to induce a healing response. Superficial defects of defined dimensions, created in adult rabbits and Goettingen miniature pigs, were investigated histologically and immunohistochemically at various time intervals after surgical intervention. The absence of cartilage repair was found to be attributable to a number of factors, including poor adhesion of repair cells to the lesion surface, limited migration and proliferative capacity of repair cells, poor spatial awareness of the aforesaid repair cells, and the incapacity of these to undergo differentiation into chondrocytes. All these limitations can be overcome by instigating a single-step treatment protocol based on the following principles: enzymatic degradation of superficial proteoglycans to expose the underlying collagenous network and thereby to improve the adhesion of repair cells to native tissue; deposition of a space-filling matrix to define the defect void and hence to facilitate its population by repair cells; inclusion of a mitogenic or chemotactic factor to attract a sufficient number of repair cells into the defect void and to induce their proliferation therein; and introduction of an encapsulated tissue-transformation factor to be released as a chondrogenic switch at an appropriate juncture during the healing process. To optimize such a treatment protocol for use in the clinical setting, many technical difficulties remain to be solved: the control of cell recruitment and numerical density, an adequate matrix scaffold, bonding of the repair to parent tissue, and triggering of a homogeneously distributed chondrogenic switch. The problems, however, are not insurmountable.