Our research team has established methods for engineering a thick, compact and synchronously contractile myocardial patch. We have used channeled scaffolds and perfusion bioreactors to maintain cell viability and function, and applied electrical stimuli to enhance functional tissue assembly (51-53). We have also shown that levels of VEGF released by retrovirally transduced cells can be controlled and utilized to drive the formation of a stable and functional vascular network (2, 3, 42, 66). We now propose to integrate these two lines of successful previous investigation into an effort focused on engineering a patch of myocardial tissue with high capacity for vascularization. Cardiac myocytes and VEGF-transduced cells will be cultured on a highly porous, channeled elastomer scaffold, using an advanced bioreactor for cardiac tissue engineering. Our first objective is to demonstrate in a rigorous nude rat model of myocardial infarction that the release of VEGF mediates the formation and maturation of a vascular network within an engineered patch. Our second objective is to generate adult human stem cells with defined profiles of VEGF release. Our third objective is to demonstrate the utility of VEGF-transduced human cells for vascularization of cardiac grafts, in the pre-established nude ratmodel. If successful, this approach would radically improve our ability to engineer vascularized tissue grafts for application in regenerative medicine.