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A crucial element of tissue engineering is to create a favorable extracellular microenvironment, mainly the extracellular matrix (ECM), to guide cell differentiation and tissue regeneration. The ECM imparts a wealth of biochemical and biomechanical cues, of which the latter can be presented in the form of nanotopography and matrix stiffness. Recent findings show that mammalian cells do respond to nanoscale features on synthetic surfaces. Our previous studies show that nanotopography can significantly influence cellular behavior ranging from morphological changes to differentiation. For example, we have demonstrated that nanotopography alone can upregulate the neuronal markers of human mesenchymal stem cells (hMSCs). A recent study has also demonstrated the important roles of topography in onedimensional and three-dimensional cell migration. In addition to topography, the extracellular microenvironment may also provide signaling cues to the anchorage-dependent cells via a feedback of local matrix stiffness. Matrix elasticity can direct hMSCs to differentiate into specific lineages: a soft matrix induces a neurogenic phenotype, while increasingly stiffer matrices inducemyogenic and osteogenic phenotypes accordingly. Taken together, the observations of nanotopography-induced and stiffnessdirected differentiation suggest that physical interactions between the cells and the extracellular environment, either in the form of topography or stiffness, or the combination thereof, can modulate cell function and stem cell differentiation. Increasing evidence indicates that cellular interaction with the ECM plays a critical role in regulating cell proliferation, differentiation, gene expression and signal transduction. At the cellmatrix interface, the mechanical force interaction between the cell and ECM occurs through the focal adhesions (FAs), which link the ECM to the contractile cytoskeleton, thereby activating FA signaling pathways. |
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