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.