Vascular tissue engineering: Bioreactor design considerations for extended culture of primary human vascular smooth muscle cells

The influence of mechanical stimulation on cell populations not only helps maintain the specific cellular phenotype but also plays a significant role during differentiation and maturation of plastic cells. This is particularly true of tissue-engineered vascular tissue, where in vivo shear forces at the blood interface help maintain the function of the endothelium. Considerable effort has gone into the design and implementation of functional bioreactors that mimic the chemical and mechanical forces associated with the in vivo environment. Using a decellularized ex vivo porcine carotid artery as a model scaffold, we describe a number of important design criteria used to develop a vascular perfusion bioreactor and its supporting process-flow. The results of a comparative analysis of primary human vascular smooth muscle cells cultured under traditional"static conditions" and "dynamic loading" are described, where the expression of MMP-2 and 9 and cathepsin-L were assessed. Continued design improvements to perfusion bioreactors may improve cellular interactions, leading to constructs with improved biological function.