Abstract
Microscale and nanoscale patterning to create substrate or matrix topography has emerged as a powerful tool for evoking specific functional behaviors in cells and tissues for applications ranging from regenerative medicine to antimicrobial coatings to adhesion modulation strategies for implantable devices. The basis for this effect, contact guidance, was discovered more than 50. years ago and has spurred scientific investigations of cell-substratum interactions based on the geometric shape, width, and depth of features at a size scale similar to subcellular features. Nanotopographic effects often work in concert with other mechanical cues such as fluid mechanical effects associated with shear and flow, substrate stiffness, and with chemical cues arising from the substrate or from surface adhesion molecules patterned along with the topographic features. Here we review the principal techniques used to generate micro- and nanotopographic features in substrates suitable for cell culture and tissue engineering. First, we review the basis for nanopatterning as a means for controlling cell behavior through mechanotransduction, followed by an analysis of nanotopographic features in the basement membrane of natural tissues. Then we cover the various classes of micro- and nanopatterning, beginning with lithographic techniques of various types, then self-assembly methods, followed by direct writing processes and finally electrospinning. Finally, various classes of applications of nanotopographic patterning are discussed, including mechanisms for controlling cell adhesion and proliferation, alignment and differentiation, and functional tissue formation. Among these examples, we will describe how emerging investigations point the way toward the use of nanotopographic patterning as a means to probe the stem cell niche and ultimately to guide stem cell fate through mechanical cues that govern processes such as adhesion, proliferation, and differentiation.