Bioreactor studies of natural and tissue engineered cartilage

Bioreactors provide controlled environments for tissue cultivation and evaluation of the effect of specific biochemical and physical parameters on in vitro chondrogenesis. The hydrodynamic environment is expected to modulate the in vitro tissue formation in at least two ways: directly via hydrodynamic effects on cell morphology and function, and indirectly via flow-induced mass transfer of nutrients and metabolites. We investigated and compared the effects of three different hydrodynamic environments: static flasks (tissues fixed in place, static medium), mixed flasks (tissues fixed in place, unidirectional turbulent flow) and rotating bioreactors (tissues dynamically suspended in laminar flow) on the morphology and composition and metabolic function of engineered and natural cartilage over an in vitro culture period of 6 weeks. In general, engineered and natural cartilage responded in a similar manner. Static conditions were associated with increased rates of GAG release into tissue culture medium and the formation of an outer fibrous capsule in both engineered and natural cartilage. In contrast, dynamic laminar flow in rotating bioreactors provided efficient oxygen supply and resulted in the retention of newly synthesized macromolecules, the maintenance of cartilaginous tissue morphology, and the best overall tissue structure and composition for both engineered and natural cartilage.