CULTIVATION OF CELL-POLYMER TISSUE CONSTRUCTS IN SIMULATED MICROGRAVITY

Tissue-engineered cartilage was cultivated under conditions of simulat ed microgravity using rotating bioreactors. Rotation randomized the ef fects of gravity on inoculated cells (chondrocytes) and permitted thei r attachment to three-dimensional (3D) synthetic, biodegradable polyme r scaffolds that were freely suspended within the vessel. After 1 week of cultivation, the cells regenerated a cartilaginous extracellular m atrix (ECM) consisting of glycosaminoglycan (GAG) and collagen types a nd II. Tissue constructs grown in simulated microgravity had higher GA G contents and thinner outer capsules than control constructs grown in turbulent spinner flasks. Two fluid dynamic regimes of simulated micr ogravity were identified, depending on the vessel rotation speed: (i) a settling regime in which the constructs were maintained in a state o f continuous free-fall close to a stationary point within the vessel a nd (ii) an orbiting regime in which the constructs orbited around the vessel spin axis. In the settling regime, the numerically calculated r elative fluid-construct velocity was comparable to the experimentally measured construct settling velocity (2-3 cm/s). A simple mathematical model was used in conjunction with measured construct physical proper ties to determine the hydrodynamic drag force and to estimate the hydr odynamic stress at the construct surface (1.5 dyn/cm(2)). Rotating bio reactors thus provide a powerful research tool for cultivating tissue- engineered cartilage and studying 3D tissue morphogenesis under well-d efined fluid dynamic conditions. (C) 1995 John Wiley and Sons, Inc.