Heart Valve Tissue Engineering: A Study of Time Varying Effects and Sample Geometry

Manuel Salinas



Mechanical conditioning has been shown to promote tissue formation in a wide variety of tissue engineering efforts. However the underlying mechanisms by which external mechanical stimuli regulate cells and tissues are not known. This is particularly relevant in the area of heart valve tissue engineering owing to the intense hemodynamic environments that surround native valves. Some studies suggest that oscillatory shear stress (OSS) caused by time-varying flow environments, play a critical role in engineered tissue formation derived from bone marrow derived stem cells (BMSCs). There is strong evidence to support this hypothesis in tissue engineering studies of bone. From observing native heart valve dynamics, OSS can be created by means of pulsatility or by cyclic specimen geometry changes. However, quantification of the individual or combined effects of these variables for the maximization of OSS environments in vitro is to date, not known. Accordingly, in this study we examined and quantified the role that i) physiologically relevant scales of pulsatility and ii) changes in geometry as a function of specimen flexure, have in creating OSS conditions for dynamic culture of tissue. A u-shaped custom made bioreactor capable of producing flow stretch and flexure was used. Computational Fluid Dynamic (CFD) simulations were performed through Ansys CFX (Ansys, Pittsburgh, PA) for both steady and pulsatile flow. We have shown that OSS can be maximized by inducing pulsatile flow over straight scaffolds. We believe that OSS promotes BMSCs tissue formation.