Development of Second Generation Tissue Engineered Vascular Grafts

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DESCRIPTION (provided by applicant): This proposal describes a 5-year training program for the development of an academic career in surgery. The principal investigator has completed surgical training at Brown University and a research fellowship in tissue engineering at Harvard University and now, will expand upon his scientific skills through a unique integration of interdepartmental resources. This program will further develop the principal investigators command of tissue engineering techniques for the treatment of cardiovascular diseases. W. Mark Saltzman will mentor the principal investigator's scientific development. Dr. Saltzman is a recognized leader in the field of tissue engineering. He is chairman of the Department of Biomedical Engineering and has trained numerous postdoctoral fellows and graduate students. Jordan S. Pober will co-mentor the principal investigator's scientific development. Dr. Pober is a recognized leader in the field of vascular biology. He is director of the Interdepartmental Vascular Biology and Transplantation Program and has trained many postdoctoral fellows including a number of surgeon-scientists. In addition, an advisory committee of highly regarded medical scientists will provide scientific and career advice. Research will focus on development of tissue engineered vascular conduits for use in bypass surgery. In this proposal we will explore the application of both drug delivery and genetic engineering principles to the design of tissue engineered vascular conduits in an attempt to inhibit the formation of neointimal hyperplasia, a leading cause of vascular graft failure. Specific aims include: 1) Establishing a model for investigating the development of neointimal hyperplasia in tissue engineered vascular grafts in vivo, 2) Determining if controlled release of sirolimus (rapamycin) from the scaffold used to construct tissue engineered vascular conduits can inhibit the development of neointimal hyperplasia, and 3) Determining if overexpression of endothelial nitric oxide synthase (eNOS) by the cells used to create tissue engineered vascular conduits can inhibit the formation of neointimal hyperplasia. Yale University provides an ideal setting for training physician scientists by incorporating expertise from diverse resources into customized programs. Such an environment maximizes the potential for the principal investigator to establish a scientific niche from which an academic career can be constructed.