This study evaluates the potential of niobium oxide–polydimethylsiloxane (PDMS) composites for tuning cellular response of fibroblasts, a key cell type of soft tissue/implant interfaces. In this study, various hybrid coatings of niobium oxide and PDMS with different niobium oxide concentrations were synthesized and characterized using scanning electron microscopy, X-ray photoelectron spectrometry (XPS), and contact angle goniometry. The coatings were then applied to 96-well plates, on which primary fibroblasts were seeded. Fibroblast viability, proliferation, and morphology were assessed after 1, 2, and 3 days of incubation using WST-1 and calcein AM assays along with fluorescent microscopy. The results showed that the prepared coatings had distinct surface features with submicron spherical composites covered in a polymeric layer. The water contact angle measurement demonstrated that the hybrid surfaces were much more hydrophobic than the original pure niobium oxide and PDMS. The combination of surface roughness and chemistry resulted in a biphasic cellular response with maximum fibroblast density on substrate with 40 wt % of niobium oxide. The results of the current study indicate that by adjusting the concentration of niobium oxide in the coating, a desirable cell response can be achieved to improve tissue/implant interfaces. © 2013 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 102A: 1478–1485, 2014.