Regulation of Myogenic Differentiation by Topologically Microgrooved Surfaces for Skeletal Muscle Tissue Engineering.

Regulation of Myogenic Differentiation by Topologically Microgrooved Surfaces for Skeletal Muscle Tissue Engineering.
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DOI:
10.1021/acsomega.1c02347
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发表时间:
2021-08-17
期刊:
影响因子:
4.1
通讯作者:
Liu S
Liu S
中科院分区:
化学3区
文献类型:
--
作者:
Gao H;Xiao J;Wei Y;Wang H;Wan H;Liu S

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受骨骼肌组织天然拓扑结构的启发,骨骼肌修复仿生支架的拓扑表面构建引起了人们极大的兴趣。以往的许多研究都集中在拓扑结构对成肌细胞的影响。然而,这些研究仅使用特定的重复大小和形状来实现成肌细胞排列和肌管形成;此外,拓扑结构的大小对成肌分化的调节作用往往被忽视,导致缺乏指导骨骼肌组织工程支架的设计。在本研究中,我们通过软光刻和熔铸相结合的方法制作了一系列不同宽度和深度的微槽形貌,并详细研究了它们对骨骼肌细胞行为,特别是肌原性分化的影响。微槽聚(乳酸-共-乙醇酸)基板被发现,有效地调节C2 C12细胞的增殖,肌源性分化,肌管形成,肌源性分化的程度显着依赖于响应于微槽结构的大小的信号。与深度相比,微槽结构的宽度对C2 C12细胞的成肌分化影响更大,且成肌细胞的分化程度随着微槽宽度的增加而增强。具有相对较大沟宽和较小沟深的微沟结构促进C2 C12细胞的肌样分化。此外,整合素介导的黏着斑激酶信号通路和MAPK信号通路在细胞中响应于外部拓扑结构而被激活,材料表面拓扑结构的大小有效调节细胞对外部拓扑结构响应的程度。这些结果对骨骼肌组织工程支架材料的设计和构建有效的骨骼肌再生仿生支架表面具有指导意义。
Inspired by the natural topological structure of skeletal muscle tissue, the topological surface construction of bionic scaffolds for skeletal muscle repair has attracted great interest. Many previous studies have focused on the effects of the topological structure on myoblasts. However, these studies used only specific repeating sizes and shapes to achieve the myoblast alignment and myotube formation; moreover, the regulatory effects of the size of a topological structure on myogenic differentiation are often neglected, leading to a lack of guidance for the design of scaffolds for skeletal muscle tissue engineering. In this study, we fabricated a series of microgroove topographies with various widths and depths via a combination of soft lithography and melt-casting and studied their effects on the behaviors of skeletal muscle cells, especially myogenic differentiation, in detail. Microgrooved poly(lactic-co-glycolic acid) substrates were found to effectively regulate the proliferation, myogenic differentiation, and myotube formation of C2C12 cells, and the degree of myogenic differentiation was significantly dependent on signals in response to the size of the microgroove structure. Compared with their depth, the width of the microgroove structures can more strongly affect the myogenic differentiation of C2C12 cells, and the degree of myoblast differentiation was enhanced with increasing groove width. Microgroove structures with relatively large groove widths and small groove depths promoted the myogenic differentiation of C2C12 cells. In addition, the integrin-mediated focal adhesion kinase signaling pathway and MAPK signaling pathway were activated in cells in response to the external topological structure, and the size of the topological structure of the material surface effectively regulated the degree of the cellular response to the external topological structure. These results can guide the design of scaffolds for skeletal muscle tissue engineering and the construction of effective bionic scaffold surfaces for skeletal muscle regeneration.
通过生物相容性聚合物基底的微槽表面有效空间分离 PC12 和 NIH3T3 细胞
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