Durable artificial small-diameter vascular grafts are a critical unmet need in a medical landscape where advanced cardiovascular diseases remain the leading causes of morbidity and mortality. As classical approaches based on maximizing biomaterial inertness have failed to overcome the thrombosis and hyperplasia that drive device failure, novel solutions inspired by the function of the native endothelium are necessary. Biomaterial devices designed for rapid in vitro or in situ endothelialization, and devices designed to mimic endothelial function are all active areas of study which will be addressed within this dissertation. Endothelial colony forming cells are an incompletely understood blood outgrowth product with tremendous potential for tissue engineering applications. This dissertation includes the novel characterization of the sensitivity of these cells to flow-independent morphological modulations, which will add to the understanding of their suitability for use in tissue engineered grafts. Additionally, using an established flowing whole-blood platform, the material thrombogenicity of novel in situ endothelializable grafts and biomolecule-modified cerebral flow diverters was quantified. Throughout this dissertation, novel analytical strategies were developed to optimize the utility of quantitative imaging modalities. This dissertation aims to improve the current understanding of both cell biology toward the development of artificial vascular graft technologies, and of assessments of material thrombogenicity, toward the development and preclinical testing of in situ endothelializable and biomimetic blood-contacting devices.