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Qiang Wei, Shenghao Wang, Feng Han, Huan Wang, Weidong Zhang, Qifan Yu, Changjiang Liu, Luguang Ding, Jiayuan Wang, Lili Yu, Caihong Zhu, Bin Li
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Figure 3. Stages in the development of research showing how matrix elasticity regulates cell behaviours. (A) The pioneering study demonstrates that human BMSCs were effectively induced to differentiate into neuronal, muscle or bone lineages when they were cultured on soft, medium, or stiff substrates. Stiffness was then considered as one of the most important mechanical cues in tissue engineering. Reprint from Engler et al.20 Copyright 2006, with permission from Elsevier. (B) In the following years, numerous biomaterials have been developed to explore cell behaviours including stem cell fate affected by substrate elasticity, and its underlying molecular mechanism. (C) In recent years, many studies began to focus on the interplay between substrate elasticity and other cues (such as topography, geometry, growth factors, etc.) and its effect on cell behaviours. In addition, to simulate dynamic changes in stiffness in vivo, biomaterials with dynamic elasticity in situ have been designed to explore mechanobiological pathways that may differ from those under static cell culture. Further, new mechanosensitive proteins have been found to be involved in the cellular responses toward matrix elasticity, including YAP, piezo, caveolin-1, etc. BMSCs: bone marrow mesenchymal stem cells; FAK: focal adhesion kinase; MAPK: mitogen-activated protein kinase; ROCK: RHO-related protein kinase 1; YAP: yes-associated protein.
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