To date, synthetic replacement approaches for soft tissue applications have involved the use of polymer formulations with surface feature dimensions in the micron range; such polymers fail to mimic the material and mechanical properties of native soft tissues. It can be hypothesized that cells of various soft tissues are accustomed to interacting with nanostructured surfaces since all soft tissues found in the body are comprised of proteins with nanometer (that is, less than 100 nanometer) lengths or diameters. Thus, the focus of the present series of investigations has been in the design and evaluation of synthetic tissue constructs which possess nanometer surface feature dimensions. Poly(lactide-co-glycolide) and poly(ether urethane) films have been successfully created with biologically inspired nanodimensional surface feature dimensions using both chemical modification and casting techniques. Results of in vitro studies with bladder and vascular cells have provided the first evidence that once surface chemistry changes were eliminated, cells adhered and proliferated better on nano, compared to conventional (or polymers with surface features greater than 100 nm), polymers. Understanding the mechanism behind these observed enhanced cellular functions on nanodimensional polymer formulations may provide a useful tool for engineering the next generation of soft tissue replacement constructs.