Gas exchange is essential for bioreactor cultivation of tissue engineered cartilage

Tissue engineered cartilage can be grown in vitro if the necessary physical and biochemical factors are present in the tissue culture environment. Cel l metabolism and tissue composition were studied for engineered cartilage c ultured for 5 weeks using bovine articular chondrocytes, polymer scaffolds (5 mm diameter x 2 mm thick fibrous discs), and rotating bioreactors. Mediu m pH and concentrations of oxygen, carbon dioxide, glucose, lactate, ammoni a, and glycosoaminoglycan (GAG) were varied by altering the exchange rates of gas and medium in the bioreactors. Cell-polymer constructs were assessed with respect to histomorphology, biochemical composition and metabolic act ivity. Low oxygen tension (similar to 40 mmHg) and low pH (similar to 6.7) were associated with anaerobic cell metabolism (yield of lactate on glucose , Y-L/G, of 2.2 mol/mol) while higher oxygen tension (similar to 80 mmHg) a nd higher pH (similar to 7.0) were associated with more aerobic cell metabo lism (Y-L/G of 1.65-1.79 mol/mol). Under conditions of infrequent medium re placement (50% once per week), cells utilized more economical pathways such that glucose consumption and lactate production both decreased, cell metab olism remained relatively aerobic (Y-L/G of 1.67 mol/mol) and the resulting constructs were cartilaginous. More aerobic conditions generally resulted in larger constructs containing higher amounts of cartilaginous tissue comp onents, while anaerobic conditions suppressed chondrogenesis in 3D tissue c onstructs. (C) 1999 John Wiley & Sons, Inc.