Micro-textured biomaterials might enhance cytocompatibility of silicon-based micro-electro-mechanical system (bio-MEMS) dummies. Photolithography-physical vapour deposition was used to produce diamond-like carbon (DLC) or Ti squares and circles on silicon, and also their inverse replicas; then DLC and Ti were compared for their guiding potential, using a SaOS-2 cell model. Scanning electron microscopy at 48 hours indicated cells were well-spread on large-sized patterns (several cells on one pattern) and assumed the geometrical architecture of underlying features. Medium-sized patterns (slightly smaller than solitary indicator cells) were inhabited by singular cells, which stretched from one island to another, assuming longitudinal or branching morphologies. On small-sized patterns (much smaller than individual cells) cells covered large micro-textured areas, but cellular filopodia bypassed the bare silicon. Immunofluorescence and confocal laser scanning microscopy indicated that the actin cytoskeleton and vinculin-containing adhesion junctions were present on the patterned areas, but not on the bare silicon. Cell density/coverage disclosed a 3.4-3.7-fold preference for the biomaterial patterns over silicon substrate (p< 0.001). Differences in the cellular response between materials were lost at 120 hours when cells were confluent. The working hypothesis was proven; enhancement by micro-patterning depends on the pattern size, shape and material and can be used to improve biocompatibility during the initial integration phase of the device.