Controlling cell orientation and morphology through topographical patterning is a phenomenon that is applicable to a wide variety of medical applications such as implants and tissue engineering scaffolds. Previous work in this field, termed contact guidance, has demonstrated the application of this cellular response on a wide variety of material substrates such as silicon, quartz, glass, and poly(di-methyl siloxane) typically using ridge-groove geometries with sharp feature edges. One limitation of these studies in terms of biomedical applications is the choice of material. Therefore, demonstrating contact guidance and topography in a biodegradable material platform is a promising strategy for controlling cellular arrangements in tissue engineering scaffolds. This study investigates several strategies to advance contact guidance strategies and technology to more practical applications. Flexible biodegradable substrates with rounded features were fabricated by replica-molding poly(glycerol-sebacate) on sucrose-coated microfabricated silicon. Bovine aortic endothelial cells were cultured on substrates with microstructures between 2 and 5 microm in wavelength and with constant feature depth of 0.45 microm. Cells cultured on substrates with smaller pitches exhibited a substantially higher frequency of cell alignment and smaller circularity index. This work documents the first known use of using a flexible, biodegradable substrate with rounded features for use in contact guidance applications. The replica-molding technique described here is a general process that can be used to fabricate topographically patterned substrates with rounded features for many biomaterials. Furthermore, these results may lead to further elucidation of the mechanism of cell alignment and contact guidance on microfabricated substrates.