Bone Morphogenetic Proteins-2,-12,and -13 Modulate in Vitro Development of Engineered Cartilage

Abstract

Bovine calf articular chondrocytes were seeded onto biodegradable polyglycolic acid (PGA) scaffolds and cultured in either control medium or medium supplemented with 1, 10, or 100 ng/mL of bone morphogenetic proteins (BMPs) BMP-2, BMP-12, or BMP-13. Under all conditions investigated, cell-polymer constructs cultivated for 4 weeks in vitro macroscopically and histologically resembled native cartilage. Addition of 100 ng/mL of BMP-2, BMP-12, or BMP-13 increased the total mass of the constructs relative to the controls by 121%, 80%, and 62%, respectively, which was accompanied by increases in the absolute amounts of collagen, glycosaminoglycans (GAG), and cells. The addition of 100 ng/mL of BMP-2, BMP-12, or BMP-13 increased the weight percentage of GAG in the constructs by 27%, 18%, and 15%, and decreased the weight percent of total collagen to 63%, 89%, and 83% of controls, respectively. BMP-2, but not BMP-12 or BMP-13 promoted chondrocyte hypertrophy. Taken together, these data suggest that BMP-2, BMP-12, and BMP-13 increase growth rate and modulate the composition of engineered cartilage and that 100 ng/mL of BMP-2 has the greatest effect. In addition, in vitro engineered cartilage provides a system for studying the effects of BMPs on chondrogenesis in a well-defined environment.