Controlled Enzymatic Matrix Degradation for Integrative Cartilage Repair: Effects on Viable Cell Density and Proteoglycan Deposition

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Abstract
Controlled enzymatic degradation has previously been shown to promote integrative repair of cartilage defect surfaces. However, side effects of such treatments could include decreases in chondrocyte viability or matrix synthesis. To explore the importance of these potential side effects, partial-thickness defects were introduced bilaterally into cartilage of the distal femur of 25 adult rabbits, previously developed treatments involving application of either chondroitinase ABC (1 U/mL) or 2.5% trypsin in saline were applied unilaterally, and rabbits were then allowed to walk freely for 2 weeks to 6 months. Before euthanasia, [(35)S]sulfate was injected into joint cavities for radiolabeling of newly synthesized cartilage proteoglycans. Vertical sections of cartilage and bone were obtained from defect areas and prepared for histological autoradiography and morphometry. Chondrocyte and cartilage morphology and cell-associated matrix proteoglycan deposition were assessed as functions of distance from introduced defects. Consistent with previous studies, chondrocyte density appeared to decrease within a 100-microm-thick region next to defects ("near") compared with control cartilage farther from the defect. Enzyme treatments strengthened the difference in cell density between regions near the defect and control regions far from it. However, for regions near defects, no significant changes in cell density were measured as a result of enzyme treatments; results suggest that creation of the defect itself has the most important long-term negative impact on nearby cell density. Furthermore, no long-term effects on cell volumes or cell-associated proteoglycan deposition due to enzyme treatments could be detected. Use of these controlled enzyme treatments may therefore be a clinically safe measure for promotion of integrative repair of articular cartilage.