Surface Roughness and Substrate Stiffness Synergize To Drive Cellular Mechanoresponse
Surface Roughness and Substrate Stiffness Synergize To Drive Cellular Mechanoresponse
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DOI：
10.1021/acs.nanolett.9b04761
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发表时间：
2020-01-01
期刊：
影响因子：
10.8
通讯作者：
Haag, Rainer
中科院分区：
文献类型：
--
作者：
Hou, Yong;Yu, Leixiao;Haag, Rainer
材料表面形貌特征已被证明对植入器械的组织再生和表面处理至关重要。许多生物材料进行了调查方面的细胞对表面粗糙度的反应。然而，由于表面形貌特征与基底弹性特征之间的相互作用不清楚，以及缺乏机理研究，有些结论甚至相互矛盾。在此，宽尺度的表面粗糙度梯度水凝胶，集成了从纳米级到微米级的表面粗糙度与可控的刚度，通过软光刻与精确的表面形态。基于这个有前途的平台，我们系统地研究了人类间充质干细胞（MSC）的机械敏感性反应，以广泛的粗糙度（200 nm至1.2 μ m的R-Q）和不同的基板刚度。我们观察到，骨髓间充质干细胞响应表面粗糙度的刚度依赖性的方式重组的表面层次结构。令人惊讶的是，细胞的机械反应和成骨作用在具有高表面粗糙度的非常软的水凝胶（3.8kPa）上明显增强，这与光滑的刚性基底相当甚至更好。这些发现扩展了我们对细胞和生物材料之间相互作用的理解，突出了通过协同物理线索调节干细胞命运的有效非侵入性方法。
Material surface topographic features have been shown to be crucial for tissue regeneration and surface treatment of implanted devices. Many biomaterials were investigated with respect to the response of cells on surface roughness. However, some conclusions even conflicted with each other due to the unclear interplay of surface topographic features and substrate elastic features as well as the lack of mechanistic studies. Herein, wide-scale surface roughness gradient hydrogels, integrating the surface roughness from nanoscale to microscale with controllable stiffness, were developed via soft lithography with precise surface morphology. Based on this promising platform, we systematically studied the mechanosensitive response of human mesenchymal stem cells (MSCs) to a broad range of roughnesses (200 nm to 1.2 mu m for R-q) and different substrate stiffnesses. We observed that MSCs responded to surface roughness in a stiffness-dependent manner by reorganizing the surface hierarchical structure. Surprisingly, the cellular mechanoresponse and osteogenesis were obviously enhanced on very soft hydrogels (3.8 kPa) with high surface roughness, which was comparable to or even better than that on smooth stiff substrates. These findings extend our understanding of the interactions between cells and biomaterials, highlighting an effective noninvasive approach to regulate stem cell fate via synergetic physical cues.