The interplay of biophysical and biochemical cues in the extracellular microenvironment regulate and control the cell fate of stem cells. Understanding the interaction between stem cells and the extracellular substrate will be crucial in controlling stem cell differentiation for regenerative medicine applications. One of the biophysical properties of the microenvironment is substrate topology, which has been demonstrated to be an important mediator of stem cell lineage regulation. Biomimetic microenvironment topology can be engineered by chemical patterning or physical patterning. The rapid advancements in nanofabrication techniques have enabled versatility in patterning types with controlled chemistries, geometries and sizes. The chapter will focus on discussing the effect on physical nanotopography on stem cell differentiation and the current theories on the topography/ mechanical force induction of stem cell differentiation possibly through integrin clustering, focal adhesion, cytoskeleton organization and the nuclear mechanosensing to sense and integrate these biophysical signals from the extracellular microenvironment.
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