Cardiovascular disease continues to be the leading cause of morbidity and mortality in this country. Disease processes involving the elastic and muscular arteries constitute the lion's share of this, with diverse pathology ranging from coronary artery disease to carotid stenosis. The most widely applied surgical intervention for affected vascular structures is openly-performed """"""""bypass"""""""" which generally employs autogenous vein for reconstruction of vessels <5 mm and prosthetic devices for larger, elastic vessels. Autogenous veins and permanent prosthetic devices have a number of intrinsic limitations for these applications, such as infection and thrombosis. A tissue engineered blood vessel conduit constructed from a synthetic biodegradable polymer scaffold that has been seeded with autologous, appropriate cell types may represent a new generation of vascular graft with measurable advantages. The applicants plan to construct large and small calibers of blood vessel conduits for reconstruction in the systemic circulation through a defined series of steps: (1) establishment of optimal cell harvest and culture conditions and analysis of the cell attachment/proliferation profiles of three categories of polymers, (2) determination of optimal methods of construct assembly and in vitro tissue cultivation using dynamic tissue culture bioreactors and (3) development of small and large animal models to permit rigorous in vivo comparison of tissue engineered blood vessels with currently available surgical technologies. Finally, the applicants will work closely with their collaborators to carry out specific cell and molecular analyses of smooth and endothelial cells in native and engineered blood vessels. While the preliminary studies have been encouraging, information concerning the cell biology of tissue engineered conduits is scant.
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