The natural cell environment provides a variety of chemical, topographical and mechanical stimuli that contribute in regulating cell behavior and function. If considerable effort has been traditionally dedicated to exploring the chemical side of cell regulation, it was more recently demonstrated that topographic cues might be equally important. Cell substratum interactions are particularly crucial in determining the reaction of cells to biomaterials, which was also shown to be strongly determined by topographical cues. A significant acceleration in investigating this aspect came from the availability of techniques for microstructured surfaces, and is now well known that cells can react to topographical features at their own scale (1-100 micron). Nevertheless, cells possess many nanoscaled features such as filopodia and a cytoskeleton, and the extracellular matrix (ECM) itself possess quite a few nanoscale details. Therefore, the capability of controlling the surface structure of materials in the nanoscale has offered the possibility of adding another level in the hierarchical understanding of cell/biomaterial interactions. Nanofabrication methods, mainly developed out of the semiconductor industries, are a technological driver for addressing the nanotopography related aspects of cell behavior. General concepts regarding some of the more widely utilized techniques that enable the achievement of ordered and well-defined nanoscale features for the investigation of cell reaction to topography are presented together with a few examples of the practical applications available in the literature.
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