Engineered Vasculature - Bridging human biology with translation

In vertebrates, blood vessels form early in development and continually sprout and remodel in order to quench the ever-increasing demands of metabolically active tissues and organs. This complex circulatory network is hierarchical, and remodeling is directed by oxygen gradients, mechanical and biochemical cues in the local microenvironment. Many human diseases are preceded or confounded by vascular dysfunction, making understanding, and predicting, pro- or anti-vasculogenic behavior imperative. Primarily, our research group employs microfabrication, tissue engineering and imaging approaches to generate and observe complex microvascular networks in vitro. Specifically, we take advantage of the autonomous behaviour of vascular endothelial cells which coalesce, connect, sprout and remodel within our microsystems. By perturbing these in vitro systems in a controlled manner, we aim to understand how tissue-specific vessels develop and remodel in healthy and disease-like states. Our results have revealed how stromal cells, growth factors, and small changes in fluid dynamics impact the behavior of human iPSC-derived, as well as primary-derived vessels. This talk will provide an overview of several microvascular models demonstrating unique cell-cell interactions and external cues that drive microvessel remodelling and changes in vascular barrier function. These reproducible, sensitive and biologically relevant microvascular systems hold promise for development into preclinical models – a major aim of our lab.