CELL ORIGIN AND DIFFERENTIATION IN THE REPAIR OF FULL-THICKNESS DEFECTS OF ARTICULAR-CARTILAGE

The origin and differentiation of cells in the repair of three-millime ter-diameter, cylindrical, full-thickness drilled defects of articular cartilage were studied histologically in New Zealand White rabbits. T he animals were allowed to move freely after the operation. Three hund red and sixty-four individual defects from 122 animals were examined a s long as forty-eight weeks postoperatively. In the first few days, fi brinous arcades were established across the defect, from surface edge to surface edge, and this served to orient mesenchymal cell ingrowth a long the long axes. The first evidence of synthesis of a cartilage ext racellular matrix, as defined by safranin-O staining, appeared at ten days. At two weeks, cartilage was present immediately beneath the surf ace of collagenous tissue that was rich in flattened fibrocartilaginou s cells in virtually all specimens. At three weeks, the sites of almos t all of the defects had a well demarcated layer of cartilage containi ng chondrocytes. An essentially complete repopulation of the defects o ccurred at six, eight, ten, and twelve weeks, with progressive differe ntiation of cells to chondroblasts, chondrocytes, and osteoblasts and synthesis of cartilage and bone matrices in their appropriate location s. At twenty-four weeks, both the tidemark and the compact lamellar su bchondral bone plate had been re-established. The cancellous woven bon e that had formed initially in the depths of the defect was replaced b y lamellar, coarse cancellous bone. Autoradiography after labeling wit h H-3-thymidine and H-3-cytidine demonstrated that chondrocytes from t he residual adjacent articular cartilage did not participate in the re population of the defect. The repair was mediated wholly by the prolif eration and differentiation of mesenchymal cells of the marrow. Intra- articular injections of H-3-thymidine seven days after the operation c learly labeled this mesenchymal cell pool. The label, initially taken up by undifferentiated mesenchymal cells, progressively appeared in fi broblasts, osteoblasts, articular chondroblasts, and chondrocytes, ind icating their origin from the primitive mesenchymal cells of the marro w. Early traces of degeneration of the cartilage matrix were seen in m any defects at twelve to twenty weeks, with the prevalence and intensi ty of the degeneration increasing at twenty-four, thirty-six, and fort y-eight weeks. Polarized light microscopy demonstrated failure of the newly synthesized repair matrix to become adherent to, and integrated with, the cartilage immediately adjacent to the drill-hole, even when light microscopy had shown apparent continuity of the tissue. In many instances, a clear gap was seen between repair and residual cartilage. This lack of physical and chemical bonding between the macromolecular components of the repair cartilage and the residual adjacent cartilag e may allow for micromotion and macromotion between them, which may in itiate cartilage degeneration. CLINICAL RELEVANCE: Knowledge of the ce ll biology of the repair of defects in articular cartilage is essentia l for the interpretation of results of therapeutic interventions desig ned to improve repair. Many rabbits had excellent histological repair in the absence of any specific treatment. We recommend strict control of experimental models by use of defects of uniform size and location to minimize variations in response. Evaluation of repair should be con tinued for six to twelve months, as it is during this period that most failures of apparently well healed cartilage occur.