In Vitro Modulation of Cartilage Shape Plasticity by Biochemical Regulation of Matrix Remodeling

Abstract

With consideration of the need for cartilage grafts of specific sizes and shapes in orthopedics and other fields, immature cartilage explants and grafts have recently been molded in vitro and in vivo. Nonsurgical correction of cartilage deformities and malformations often uses mechanical stimuli and further demonstrates the plasticity of cartilage shape. Cartilage shape plasticity appears to diminish with maturation, coincident with changes in matrix composition. This study's objectives were to characterize shape plasticity of articular cartilage from immature and mature bovines and test whether altering proteoglycan and collagen (COL) remodeling modulates shape plasticity in vitro. Cartilage explants were analyzed fresh on day 0 or after 14 days of culture in the presence of β-d-xyloside to suppress glycosaminoglycan accumulation or β-aminopropionitrile (BAPN) to inhibit lysyl oxidase-mediated COL crosslinking. Culture with β-d-xyloside and BAPN differentially regulated cartilage size, composition, and shape plasticity, with an inverse association between shape plasticity and the ratio of tissue COL to glycosaminoglycan. Retention of a mechanically imposed contour was increased by culture with BAPN compared to day 0 calf cartilage (90% vs. 69%), and BAPN-treated samples had higher shape retention than β-d-xyloside-treated samples for both calf (90% vs. 74%) and adult cartilage (54% vs. 31%). The findings provide quantitative measures of cartilage shape plasticity at immature and mature stages and are consistent with the concept of diminishing shape plasticity with maturation. The ability to modulate cartilage shape plasticity by varying in vitro biochemical conditions may be a useful tool for the formation of contoured chondral grafts.