REPAIR OF PARTIAL-THICKNESS DEFECTS IN ARTICULAR-CARTILAGE - CELL RECRUITMENT FROM THE SYNOVIAL-MEMBRANE

Partial-thickness defects evolving in mature articular cartilage do no t heal spontaneously. This type of defect was created in the articular cartilage of adult rabbits and Yucatan minipigs, and the effects of c hondroitinase ABC or trypsin, fibrin clots, and mitogenic growth facto rs on the healing process were examined histologically at intervals ra nging from one to forty-eight weeks. The effect of chondroitinase ABC or trypsin was examined initially. Articular cartilage contains macrom olecules, including proteoglycans, which render the surfaces of this t issue, and of partial-thickness defects within it, antiadhesive. Chond roitinase ABC digests the glycosaminoglycan chains of cartilage proteo glycans, and trypsin degrades their core proteins. To test the hypothe sis that mesenchymal cells may be prevented from adhering to and migra ting over the surfaces of partial-thickness defects by proteoglycans, we removed a superficial layer of these macromolecules from the surfac e of the defect with use of one of these enzymes. The treatment evoked an increase in the coverage of the defect surface with mesenchymal ce lls; when combined with the local application of a mitogenic growth fa ctor (basic fibroblast growth factor, transforming growth factor-beta 1, epidermal growth factor, insulin-like growth factor-1, or growth ho rmone), the coverage was more extensive but mesenchymal cells did not extend into and completely fill the volume of the defect. When the sur face of the defect was treated with chondroitinase ABC and the cavity of the defect was filled with a fibrin clot to furnish a matrix or sca ffolding for the migration of cells therein, there was migration and p roliferation of cells throughout the volume of the defect but at a low population density. Mesenchymal cells remodeled the deposited fibrin matrix, which was replaced by a loose fibrous connective tissue. When defects that had been treated with chondroitinase ABC were filled with a fibrin clot containing a mitogenic growth factor, mesenchymal cells filled the entire cavity of the defect, and the density of the cells was greatly increased, particularly when transforming growth factor-be ta 1 was used. Histological studies revealed a continuous layer of mes enchymal cells extending from the synovial membrane across the superfi cial tangential zone of normal articular cartilage into the defect, in dicating that the cells that were recruited for the repair process wer e of synovial origin. At forty-eight weeks, the entire cavity of the d efect remained filled with a fibrous connective tissue. CLINICAL RELEV ANCE: The partial-thickness defects created in articular cartilage in this study are analogous to the clefts and fissures manifested during the early stages of osteoarthrosis; neither heal spontaneously. If the development of early defects could be impeded or arrested by elicitin g a repair response, then exacerbation of the pathological condition m ight be prevented. We describe a procedure for evoking the ingrowth of mesenchymal cells from the synovial membrane into such defects, where they lay down a loose fibrous connective tissue. Conditions to induce their differentiation into chondrocytes, thus promoting the formation of hyaline cartilage, must now be defined.