Frontiers in tissue engineering - In vitro modulation of chondrogenesis

Cartilage tissue engineering can provide functional cartilaginous construct s that can be used for controlled in vitro studies of chondrogenesis and po tentially for in vivo articular cartilage repair. Ideally, engineered carti lage should be indistinguishable from native articular cartilage with respe ct to zonal organization, biochemical composition, and mechanical propertie s. In the model system presented here, chondrogenic cells are expanded in v itro as required, seeded onto three-dimensional polymeric scaffolds, and cu ltured in bioreactor vessels. During the course of in vitro cultivation, co nstruct cellularity plateaus at a physiologic level, fractions of glycosami noglycan and Type II collagen increase progressively, and the scaffold biod egrades. Construct structure (composition, morphology) and function (biosyn thetic activity, mechanical properties) depend on cultivation conditions. T his paper reviews recent studies of in vitro modulation of chondrogenesis b y: (1) cell seeding density and source: (2) the tissue regeneration templat e; (3) biochemical regulatory signals; (4) mixing, mass transport and hydro dynamic forces; and (5) cultivation time. Key requirements and some of the critical research needs for successful cartilage tissue engineering are dis cussed.