| This work uses finite element models of fluid flow to reveal new mechanisms for normalizing the phenotype of engineered microvasculature in vitro, and to design networks of engineered microvessels using established properties of the microvasculature. In concert with in vitro experiments, computer models validated a novel theory: that the mechanical stability of the engineered microvessel depends in part on how well it expresses strong barrier function. In a similar fashion, models validated a second experimentally derived theory concerning those properties: wall-shear stress enhances barrier function, and, independently, transmural pressure enhances the stability of the vessel wall.;Models were also used to predict a series of designs for systems of microvessels based on one of two design principles. The first principle was that elevation of transmural pressure above a threshold value was necessary to prevent collapse of the vessel wall. The second principle was that the volume of the vasculature in an optimal design should be minimized, but only so far that oxygen concentration remains above a threshold level in the tissue construct.;This dissertation exemplifies steps in a sequence of refinement that can be used to systematically span the gap between current practices in vascular tissue engineering and clinical application. |
