Convective Flow Tissue Assembly of Vascular Grafts

Coronary heart disease accounts for the largest fraction of heart disease (the leading cause of death in the United States, affecting 12 million Americans) and has an annual cost to society that exceeds 110 billion dollars. There is a great clinical need for small diameter vascular artery grafts, as patients requiring multiple or repeat bypass procedures frequently lack adequate autogenous vessels to serve as bypass conduit. Tissue engineering clearly has the potential to provide relief in this area, however, present attempts have had limited clinical potential, due to practicality and feasibility issues or involvement of foreign materials. As such, a novel tissue assembly methodology that avoids these pitfalls is proposed. The new methodology relies upon drag-induced convective flow to assemble tissue on an inert porous mandrel, which is later removed, yielding completely biological constructs. The flow will be generated by a transmural pressure gradient, which in turn will generate shear stresses that will mimic the mechanical environment of native arteries. The tissue assembly methodology will allow for multiple seedings, such that the culture of layered tissues is possible, and will be readily scaled up and automated, allowing for wide-scale commercial and clinical application. The present Phase I proposal seeks to test the ability of the novel bioreactor design to assemble human smooth muscle cells into thick, healthy three-dimensional tissue constructs. These constructs will be evaluated in terms of physical and morphological properties. The ultimate goal is to develop a tissue assembly method that produces autologous and completely biological vascular grafts, which are produced with consistent biological and mechanical properties, by a manufacturing process that can be readily scaled-up in an economic manner.