The current techniques used to create patterned materials at the nanometer scale such as electron beam lithography are restricted to patterning small areas, which can be expensive and time consuming. A simple, cost-effective approach has been developed to create a reproducible surface topography to influence the cellular response. In this study, the cellular response of murine fibroblasts to 7, 14 and 21 nm colloidal silica particles were investigated over one, three and seven days and up to seven weeks. The surface topography and wettability of the surfaces were also studied. The results confirmed that silica particles create a nanoscale topography, which initiates a distinctive cellular response affecting the morphology, adhesion and proliferation of the fibroblasts. The effect was evident up to seven weeks with no adverse effects on cell viability.