Paul M. Gross Distinguished Professor and Chair, Biomedical Engineering Duke University Durham, North Carolina, United States
Introduction: : The differentiation, morphogenesis, and homeostasis of blood vessels occur in a complex and dynamic environment. As a result, the microenvironment plays a crucial role in vascular development and regeneration, which can be disrupted by injury or disease. Understanding how this microenvironment influences cellular decisions can help us create improved models that mimic both healthy and diseased blood vessels, as well as develop countermeasures to prevent deterioration and therapeutics to guide regeneration.
Materials and
Methods: : We develop in vitro 3D models to study how physicochemical cues and signaling pathways affect vascular differentiation, assembly, and function. These models use biomaterials that mimic both chronic and acute hypoxia, the viscoelasticity and stiffness of the extracellular matrix, and materials designed for conduit fabrication. We incorporate stem cell derivatives of endothelial cells, pericytes, and smooth muscle cells to form a functional vasculature.
Results, Conclusions, and Discussions:: Our studies establish detailed and complex microphysiological systems that uncover specific mechanisms by which the vasculature responds to various stressors, including a decrease in oxygen levels and changes in extracellular matrix mechanics. Using these microphysiological blood vessel systems improves our understanding of their functions in tissue performance, aging, disease, and regeneration.
