This proposal describes a five-year training program for the development of an academic career in vascular tissue engineering. The principal investigator is an accomplished vascular surgeon who has begun a basic science effort centered around the creation of a small-caliber vascular graft. Now, through a unique integration of interdepartmental resources, the principal investigator will expand his scientific skills to yield translational research. The program focuses on the creation and in vivo testing of a novel vascular graft. Irving Shapiro, PhD, Director of Jefferson's Cell and Tissue Engineering Program, will sponsor the principal investigator's scientific development along with Thomas Tulenko, PhD, Director of Jefferson's Cardiovascular Biology Research Program. Dr. Shapiro is a leader in the field of bone and cartilage tissue engineering, while Dr. Tulenko's expertise resides in vascular cell biology and cardiovascular disease. Both have extensive experience in training postdoctoral fellows and graduate students. To enhance the program, the investigator will work with Christopher Adams, PhD, an expert in electron and laser confocal microscopic analysis of tissue-engineered constructs;James San Antonio, PhD, an authority in endothelial cell-matrix interactions;and Yi Shi, MD, PhD, an expert in vascular graft remodeling. Keith Danielson, PhD, and Ronald Weigel, MD, PhD, scientists in stem cell engineering and cancer biology, respectively, will further advise and direct the investigator's educational program. The scientific goal of the project is to construct and test a novel small-caliber vascular bypass graft, created by seeding a natural vascular tissue scaffold (decellularized cadaver vein) with autologous microvessel endothelial cells derived from adipose tissue.
The specific aims i nclude determining: 1) the optimal scaffold design and media conditions for endothelial cell seeding, 2) the optimal paradigm for graft creation, and 3) the durability and healing characteristics of the seeded graft in vivo. Resources from the Jefferson's Cell and Tissue Engineering and Cardiovascular Research Laboratories provide the ideal setting for training physician-scientists in the field of vascular tissue engineering. This environment maximizes the potential for the principal investigator to achieve independence in a field with translational applicability.