<br>成骨诱导化学信号增强人间充质干细胞在微形貌图案表面上成骨分化的机械敏感性,Advanced Science

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成骨诱导化学信号增强人间充质干细胞在微形貌图案表面上成骨分化的机械敏感性
Advanced Science ( IF 14.3 ) Pub Date : 2022-04-04 , DOI: 10.1002/advs.202200053
Jianxiang He ₁ , Dongqi You ₁ , Qi Li ₁ , Jiabao Wang ₂ , Sijia Ding ₁ , Xiaotong He ₁ , Haiyan Zheng ₁ , Zhenkai Ji ₂ , Xia Wang ₁ , Xin Ye ₁ , Chao Liu ₁ , Hanyue Kang ₂ , Xiuzhen Xu ₂ , Xiaobin Xu ₂ , Huiming Wang _{1,

3} , Mengfei Yu ₁

Affiliation

机械信号因其全面、广泛和非侵入性的优势而被广泛用于调节细胞行为。然而，与化学线索不同，机械线索不足以有效地独立确定细胞命运，并且提高细胞的机械敏感性相当具有挑战性。在这项研究中，研究了化学和机械信号对人类间充质干细胞成骨分化的综合影响。这些结果表明，化学信号（例如成骨介质的存在）诱导细胞分泌更多胶原蛋白，并诱导整合素招募粘着斑蛋白，这些蛋白在支架材料的机械力的帮助下成熟并级联一系列事件。使用双层光刻技术的高分辨率、高度有序的中空微截头体阵列，结合载有预定义可溶性化学物质的改性甲基丙烯酸酯明胶，为细胞提供化学和机械线索。这种方法最终促进了细胞骨分化的实现，并提高了小鼠体内股骨骨折模型的骨修复效率。此外，结果还揭示了整合素α2/粘着斑激酶/Ras同源基因家族成员A/大肿瘤抑制因子1/Yes相关蛋白在人间充质干细胞体外和体内成骨分化中的关键作用。总的来说，这些结果表明化学线索增强了细胞的微地形敏感性。

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Osteogenesis-Inducing Chemical Cues Enhance the Mechanosensitivity of Human Mesenchymal Stem Cells for Osteogenic Differentiation on a Microtopographically Patterned Surface

Mechanical cues are widely used for regulating cell behavior because of their overarching, extensive, and non-invasive advantages. However, unlike chemical cues, mechanical cues are not efficient enough to determine cell fate independently and improving the mechanosensitivity of cells is rather challenging. In this study, the combined effect of chemical and mechanical cues on the osteogenic differentiation of human mesenchymal stem cells is examined. These results show that chemical cues such as the presence of an osteogenic medium, induce cells to secrete more collagen, and induce integrin for recruiting focal adhesion proteins that mature and cascade a series of events with the help of the mechanical force of the scaffold material. High-resolution, highly ordered hollow-micro-frustum-arrays using double-layer lithography, combined with modified methacrylate gelatin loaded with pre-defined soluble chemicals to provide both chemical and mechanical cues to cells. This approach ultimately facilitates the achievement of cellular osteodifferentiation and enhances bone repair efficiency in a model of femoral fracture in vivo in mice. Moreover, the results also reveal these pivotal roles of Integrin α2/Focal adhesion kinase/Ras homolog gene family member A/Large Tumor Suppressor 1/Yes-associated protein in human mesenchymal stem cells osteogenic differentiation both in vitro and in vivo. Overall, these results show that chemical cues enhance the microtopographical sensitivity of cells.

更新日期：2022-04-04

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