Abstract
Understanding cell–extracellular matrix interactions is crucial to the repair or replacement of cells, tissues and organs. The fate of cells can be dictated by the in vivo cellular microenvironment, which provides biophysical (topography), biomechanical (substrate elasticity and flow-induced forces) and biochemical (cytokines and growth factors) cues to regulate the phenotype and function of cells. For example, basement membranes manifest a complex three-dimensional (3D) texture with sizes in the nanometer range. In addition to inducing pronounced changes to cell morphology and, consequently, gene and protein expression, nanotopographical cues could potentially help induce the differentiation of stem cells into certain lineages. This review covers the commonly used techniques of engineering nanotopography, surveys cellular responses to nanotopography with the focus on the effects of dimensions, shape and order of nanotopographical cues relative to cell dimensions, and discusses possible mechanism by which cells sense nanotopography and the challenges in translating the mechanistic understanding of nanoscale modulation of cell behavior to regenerative medicine. Delineation of cell–matrix interactions in the physiological, 3D environment will help advance the field of regenerative medicine.
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