To investigate the potential utility of mechanical loading in articular cartilage tissue engineering, porous type II collagen scaffolds seeded with adult canine passaged chondrocytes were subjected to static and dynamic compressions of varying magnitudes (0-50% static strain) and durations (1-24 h), and at different times during culture (2-30 days postseeding). The effects of mechanical compression on the biosynthetic activity of the chondrocytes were evaluated by measuring the amount of (3)H-proline-labeled proteins and (35)S-sulfate-labeled proteoglycans that accumulated in the cell-scaffold construct and was released to the medium during the loading period. Similar to published results on loading of articular cartilage explants, static compression decreased protein and proteoglycan biosynthesis in a time- and dose-dependent manner (each p < 0.005), and selected dynamic compression protocols were able to increase rates of biosynthesis (p < 0.05). The main difference between the results seen for this tissue engineering system and cartilage explants was in the amount of newly synthesized matrix molecules that accumulated within the construct under dynamic loading, with less accumulating in the type II collagen scaffold. In summary, the general biosynthetic response of passaged chondrocytes in the porous type II collagen scaffolds is similar to that seen for chondrocytes in their native environment. Future work needs to be directed to modifications of the cell-seeded construct to allow for the capture of the newly synthesized matrix molecules by the scaffold.

Summary:This study utilizes a canine model to quantify changes in articular cartilage 15-18 weeks after a knee joint is subjected to surgical treatment of isolated chondral defects. Clinical and experimental treatment of articular cartilage defects may include implantation of matrix materials or cells, or both. Three cartilage repair methods were evaluated: microfracture, microh-acture and implantation of a type-I1 collagen matrix. and implantation of an autologous chondrocyte-seeded collagen matrix. The properties of articular cartilage in other knee joints subjected to harvest of arlicular cartilage lrom the trochlear ridge (to obtain cells for the cell-seeded procedure) were also evaluated. Physical properties (thickness, equilibrium compressive modulus, dynamic compressive stiffness, and streaming potential) and biochemical composition (hydration, glycosaminoglycan content, and DNA content) of the cartilage from sites distant to the surgical treatment were compared with values measured for site-matched controls in untreated knee joints. N o significant differences were secn in joints subjected to any of the three cartilage repair procedures. However, a number of changes were induced by the harvest operation. The largest changes (displaying up to 3-fold increases) were seen in dynamic stiffness and streaming potential of patellar groove cartilage from joints subjected to the harvest procedure. Whether the changes reported will lead to osteoarthritic degeneration is unknown, but this study provides evidence that the harvest procedure associated with autologous cell transplantation for treatment of chondral defects may result in changes in the articular cartilage in the joint.