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During development and tissue repair, progenitor cells are guided by both biochemical and biophysical cues of their microenvironment, including topographical signals. The topographical cues have been shown to play an important role in controlling the fate of cells. Systematic investigation of topographical structures with different geometries and sizes under the identical experimental conditions on the same chip will enhance the understanding of the role of shape and size in cell-topography interactions. A simple customizable multi-architecture chip (MARC) array is therefore developed to incorporate, on a single chip, distinct topographies of various architectural complexities, including both isotropic and anisotropic features, in nano- to micrometer dimensions, with different aspect ratios and hierarchical structures. Polydimethylsiloxane (PDMS) replicas of MARC are used to investigate the influence of different geometries and sizes in neural differentiation of primary murine neural progenitor cells (mNPCs). Anisotropic gratings (2 μm gratings, 250 nm gratings) and isotropic 1 μm pillars significantly promote differentiation of mNPCs into neurons, as indicated by expression of β-III-tubulin (59%, 58%, and 58%, respectively, compared to 30% on the control). In contrast, glial differentiation is enhanced on isotropic 2 μm holes and 1 μm pillars. These results illustrate that anisotropic topographies enhance neuronal differentiation while isotropic topographies enhance glial differentiation on the same chip under the same conditions. MARC enables simultaneous cost-effective investigation of multiple topographies, allowing efficient optimization of topographical and biochemical cues to modulate cell differentiation., (Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

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., (Copyright (c) 2010 Elsevier Inc. All rights reserved.)