Mechanobiology of engineered cartilage cultured under a quantified fluid-dynamic environment

Abstract

Natural cartilage remodels both in vivo and in vitro in response to mechanical forces and hence mechanical stimulation is believed to have a potential as a tool to modulate extra-cellular matrix synthesis in tissue-engineered cartilage. Fluid-induced shear is known to enhance chondrogenesis on animal cells. A well-defined hydrodynamic environment is required to study the biochemical response to shear of three-dimensional engineered cell systems. We have developed a perfused-column bioreactor in which the culture medium flows through chondrocyte-seeded porous scaffolds, together with a computational fluid-dynamic model of the flow through the constructs' microstructure. A preliminary experiment of human chondrocyte growth under static versus dynamic conditions is described. The median shear stress imposed on the cells in the bioreactor culture, as predicted by the CFD model, is 3 × 10⁻³ Pa (0.03 dyn/cm²) at a flow rate of 0.5 ml/min corresponding to an inlet fluid velocity of 44.2 μm/s. Providing a fluid-dynamic environment to the cells yielded significant differences in cell morphology and in construct structure.