EFFECT OF STATIC COMPRESSION ON PROTEOGLYCAN BIOSYNTHESIS BY CHONDROCYTES TRANSPLANTED TO ARTICULAR-CARTILAGE IN-VITRO

Transplantation of chondrocytes by injection or within carrier matrice s has shown promise for augmenting the repair of articular cartilage d efects. In vivo, transplanted chondrocytes are exposed to mechanical f orces. This in vitro study examined the effect of a step application o f compressive load to chondrocytes after the cells had been seeded ont o a cartilage surface. Bovine chondrocytes were transplanted onto bovi ne cartilage disks, allowed to attach for 1 hour or 4 days, and subjec ted to compression through overlying cartilage disks in a confined com pression configuration. Before use, the disks were lyophilized to lyse the endogenous chondrocytes and thereby allow assessment of the metab olic activity of the transplanted cells. During a 16-hour application of compressive stress of 0.24-0.72 MPa, proteoglycan synthesis, assess ed as [S-35]sulfate incorporation into macromolecules, was inhibited b y approximately 68% after the 1-hour attachment and by approximately 4 5% after the 4-day attachment. Cell retention after the application of load was assessed by use of [H-3]thymidine-tagged chondrocytes and qu antitation of the displacement of radioactivity. After the 1-hour seed ing period, loading induced a dose-dependent dislodgment of [H-3]radio activity (as much as 35%) from the tissue bilayer. In contrast, after the 1-day seeding period, there was no detectable effect of loading on chondrocyte dislodgment with an 8-12% release of radioactivity. The i nhibitory effect of a 16-hour compression of 0.48 MPa applied after th e 4-day seeding period was studied further. This protocol did not appe ar to have an irreversible effect on chondrocyte metabolism; at 2 days after the release of load, proteoglycan synthesis by the loaded cells was stimulated by 41% compared with transplanted cells that were not subjected to loading. These results suggest that the application of st atic compressive stress to chondrocytes at a cartilage surface may aff ect biosynthesis by these cells and thus subsequent integrative cartil age repair. Such an effect may have implications for optimization of t he tightness of the press fit of a cell-laden cartilaginous construct into an articular defect.