The incorporation of biological function into synthetic polymers provides particular potential for advances in studying the complex interactions between biomolecules and materials. We developed a simple method to create polymer with submicron features on surface of polystyrene-co-maleic anhydride (PSMAA) using a combination of phase-separation and spin coating method. The nanostructured PSMAA which was rarely utilized as biomaterials was further functionalized by doping with dopamine or by treating with nitrogen containing plasma. This study demonstrated a straightforward method that the creation of topographical cues alone improves the biocompatibility of PSMAA thin film. The cell proliferation increased more significantly to
1.8- and 2.5-fold on dopamine blended and N2/H2 plasma treated PSMAA films when compared to that on the flat sample, respectively. The overall results showed that the integration of microenvironment and chemical functionalities into materials provide promising effects for promoting mammalian cell growth.