Effects of mixing on the composition and morphology of tissue-engineered cartilage

Cartilage constructs were grown using isolated chondrocytes and biodegradable polymer scaffolds made of fibrous polyglycolic acid in the form of 1-cm-dia X 5-mm-thick discs. The scaffolds were seeded in a mixed cell suspension and cultured for up to 8 weeks under static or mired tissue culture conditions in petri dishes and spinner flasks. Turbulent mixing significantly improved the biochemical compositions and altered morphologies of the cartilage constructs, which were the thickest ones cultured to date in vitro. Constructs from mired cultures were more regular in shape and contained up to 70% more cells, 60% more sulfated glycosaminoglycan, and 125% more total collagen when compared to constructs from static cultures. Mixing also induced the formation of an outer capsule with multiple layers of elongated cells and collagen fibrils around the inner tissue phase, while statically grown constructs consisted of round cells embedded in cartilaginous matrix. Mixing during cell seeding and tissue culture is thus an important parameter for the cultivation of tissue-engineered cartilage in a range of sizes, shapes and compositions for a variety of clinical applications (e.g, fibrous cartilage for reconstructive surgery or articular cartilage for joint resurfacing).