Biomaterials that successfully integrate into surrounding tissue should match not only the tissue's mechanical properties, but also the dimensions of the associated nano-structured extra-cellular matrix (ECM) components. The goal of this research was to use these ideals to develop a synthetic, nano-structured, polymeric biomaterial that has cytocompatible and mechanical behaviors similar to that of natural vascular tissue. In a novel manner, poly-lactic acid/polyglycolic acid (PLGA) (50/50 wt.% mix) and polyurethane were separately synthesized to possess a range of fiber dimensions in the micron and nanometer regime. Preliminary results indicated that decreasing fiber diameter on both PLGA and PU enhanced arterial smooth muscle cell adhesion; specifically, arterial smooth muscle cell adhesion increased 23% when PLGA fiber dimensions decreased from 500 to 50 nm and increased 76% on nano-structured, compared to conventional structured, polyurethane. However, nano-structured PLGA decreased endothelial cell adhesion by 52%, whereas adhesion of these same cells was increased by 50% on polyurethane. For these reasons, the present in vitro study provides the first evidence that polymer fiber dimensions can be used to selectively control cell functions for vascular prosthesis.