Engineering Patterns To Study Vascular Biology

Proper growth of blood vessels is critical for development, wound healing and homeostasis. This process is regulated by a variety of microenvironmental cues including growth factor signaling, cell-cell contacts and mechanical and biochemical signals from the extracellular matrix. The work presented in this dissertation encompasses the application of engineering principles to the study of angiogenesis and vascular biology within the contexts of tissue engineering and vascular disease. In Chapter 2, we present a novel strategy for generating a spatially patterned vascular network in vivo. Future development of clinically viable engineered tissues hinges on the ability to generate functional vasculature capable of delivering blood to parenchymal cells deep within the tissue. The vascularization strategy described here utilizes tissue constructs that contain patterned ‘cords ’ of endothelial cells. Implantation of these constructs into mice leads to the formation of stable capillaries in a spatially controlled geometry. The capillaries become perfused with host blood as early as 3 days post implantation, remain stable for at least 28 days in vivo, are largely comprised of implanted endothelial cells, and are invested by α-SMA positive pericytes. We further demonstrate that spatial patterning of vascular architecture improves the function of engineered hepatic tissues. Specifically, co-implantation of patterned endothelial cell cords with primar