In Vitro Synthesis of a Microvascular Network

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DESCRIPTION (provided by applicant): This two-year proposal describes the development of processes, based on microlithography, to synthesize a human dermal microvascular network in vitro. The methods developed in this work will support the following long-term goals: 1) modeling of human inflammatory responses in vitro for high-throughput screening of agents that can reverse an induced response, and 2) engineering of full-thickness skin grafts with an integrated vasculature. By allowing the synthesis of tissue with a controlled microscale architecture, these lithographic methods will complement current strategies in tissue engineering that rely on cellular self-organization induced by growth factors. The proposed schemes will arrange primary microvascular cells into a three-dimensional network of open tubes initially, and then continuously perfuse the construct to allow its maturation into a functional microcirculation. We will determine the ranges of network shear stress, luminal pressure, and oxidative stress that enable the as-synthesized construct to develop a histological organization characteristic of a human dermal microvascular bed. Moreover, we will vary perfusion conditions to tune the reactivity of the in vitro network to inflammatory cytokines, and to enhance the extravasation of neutrophils in a stimulated network. This work will further determine the thickness of tissue that can be sustained metabolically by an engineered microvascular construct comprised of two interconnected plexuses.