Our long-term goal is to engineer vascular composite allografts using patient specific cells for repairing composite tissue defects. The goal of this project is to construct a dermo-epidermal skin substitute (DESS) that is vascularized and repopulated with skin cells. The central hypothesis to be tested here is that the natural skin scaffold can be extensively repopulated with skin cells and that these grafts can serve as alternatives to composite vascular allografts in vitro and in vivo. The rationale of the study is that while most past biomaterials research has focused on producing the ideal scaffold from the ground up using synthetic materials, the native extracellular matrix (ECM), de facto, contains much of necessary architecture and environmental cues absent from synthetic matrices, and hence presents a promising, more realistic alternative approach for producing engineered tissue substitutes, which can vertically advance the field of skin tissue engineering. Our approach will be to perfusion decellularize a porcine fasciocutaneous flap to prepare an extracellular matrix scaffold which will then be repopulated with skin cells (e.g., keratinocytes, dermal fibroblasts, mesenchymal stem cells and endothelial cells) either primary or derived from patient specific induced pluripotent stem (iPS) cells.