Cells can respond to different topographical cues in their natural microenvironment. Hence, scientists have employed microfabrication techniques and materials to generate culture substrates containing topographies for cell-based assays. However, one of the limitations of custom topographical platforms is the lack of adoption by the broad research community. These techniques and materials have high costs, require high technical expertise, and can leach components that may introduce artifacts. In this study, we developed an array of culture surfaces on polystyrene using razor printing and sanding methods to examine the impact of microscale topographies on cell behavior. The proposed technology consists of culture substrates of defined roughness, depth, and curvature on polystyrene films bound to the bottom of a culture well using double-sided medical-grade tape. Human monocytes and adult mesenchymal stem cells (hMSCs) were used as test beds to demonstrate the applicability of the array for cell-based assays. An increase in cell elongation and Arg-1 expression was detected in macrophages cultured in grooves and on rough substrates as compared to flat surfaces. Also, substrates with enhanced roughness stimulated the proliferation of hMSCs. This effect correlated with the secretion of proteins involved in cell proliferation and the downregulation of those associated with cell differentiation. Our results showed that the polystyrene topography sticker array supports cellular changes guided by microscale surface roughness and geometries. Consequently, microscale surface topographies on polished and razor-printed polystyrene films could leverage the endogenous mechanisms of cells to stimulate cellular changes at the functional level for cell-based assays.