Mechanical compression modulates proliferation of transplanted chondrocytes

The presence of an appropriate number of reparative cells in an articular c artilage defect is probably necessary for consistent and successful repair. Following the transplantation of chondrocytes into a defect, cell prolifer ation may modulate local defect cellularity. Transplanted cells can be comp ressed during cartilage repair as a result of joint-loading or press-fittin g a graft into a cartilage defect. The objective of this study was to chara cterize the proliferative response of chondrocytes after attachment to cart ilage and application of static compressive stress between cartilaginous su rfaces in an es vivo model. The chondrocytes were isolated from adult bovin e cartilage, cultured in high-density monolayer, resuspended, and then tran splanted onto the surface of devitalized cartilage at a density of 250,000 cells/cm(2). The total DNA content of transplanted cell layers increased st eadily to a plateau by 5 days and represented a 4-fold increase in cell num ber during incubation in medium including serum and ascorbate. Over the cul ture period, the level of DNA synthesis ([H-3]thymidine incorporation), on a per cell basis, decreased steadily (88% between days 0 and 6). The applic ation of 24 hours of static compressive stress (0.06-0.4 MPa) to the adhere nt cells at 1 and 4 days after transplantation inhibited overall DNA synthe sis by 70-similar to 87% compared with unloaded controls. After release fro m load, cell proliferation generally remained at low levels. The marked pro liferation of chondrocytes when attached to cartilage without applied load and the inhibition of this proliferation by relatively low-amplitude static compressive stress may be relevant to the occasional overgrowth of tissue in some chondrocyte transplantation procedures. The dosimetry of these effe cts suggests that the in vivo mechanical environment may have a marked effe ct on proliferation of transplanted chondrocytes.