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低刚度三维打印Ti2448通过调节巨噬细胞极化Piezo1/YAP信号轴增强血管生成和成骨作用

Three-Dimensionally Printed Ti2448 With Low Stiffness Enhanced Angiogenesis and Osteogenesis by Regulating Macrophage Polarization Piezo1/YAP Signaling Axis.

作者信息

Tang Zhen, Wei Xinghui, Li Tian, Wu Hao, Xiao Xin, Hao Yulin, Li Shujun, Hou Wentao, Shi Lei, Li Xiaokang, Guo Zheng

机构信息

Department of Orthopaedics, Xijing Hospital, Fourth Military Medical University, Xi'an, China.

School of Basic Medicine, Fourth Military Medical University, Xi'an, China.

出版信息

Front Cell Dev Biol. 2021 Nov 15;9:750948. doi: 10.3389/fcell.2021.750948. eCollection 2021.

Abstract

Previous studies have found that the novel low-elastic-modulus Ti2448 alloy can significantly reduce stress shielding and contribute to better bone repair than the conventional Ti6Al4V alloy. In this study, the promotion of osteogenesis and angiogenesis by three-dimensionally printed Ti2448 were also observed . However, these were not significant in a series of tests. The stiffness of materials has been reported to greatly affect the response of macrophages, and the immunological regulation mediated by macrophages directly determines the fate of bone implants. Therefore, we designed more experiments to explore the role of three-dimensionally printed Ti2448 in macrophage activation and related osteogenesis and angiogenesis. As expected, we found a significant increase in the number of M2 macrophages around Ti2448 implants, as well as better osteogenesis and angiogenesis . studies also showed that macrophages pre-treated with Ti2448 alloy significantly promoted angiogenesis and osteogenic differentiation through increased PDGF-BB and BMP-2 secretion, and the polarization of M2 macrophages was enhanced. We deduced that Ti2448 promotes angiogenesis and osteogenesis through Piezo1/YAP signaling axis-mediated macrophage polarization and related cytokine secretion. This research might provide insight into the biological properties of Ti2448 and provide a powerful theoretical supplement for the future application of three-dimensionally printed Ti2448 implants in orthopaedic surgery.

摘要

先前的研究发现,新型低弹性模量Ti2448合金与传统的Ti6Al4V合金相比,能显著减少应力遮挡,并有助于更好的骨修复。在本研究中,还观察到三维打印的Ti2448对成骨和血管生成的促进作用。然而,在一系列测试中,这些作用并不显著。据报道,材料的刚度会极大地影响巨噬细胞的反应,而巨噬细胞介导的免疫调节直接决定了骨植入物的命运。因此,我们设计了更多实验来探究三维打印的Ti2448在巨噬细胞激活以及相关成骨和血管生成中的作用。正如预期的那样,我们发现Ti2448植入物周围的M2巨噬细胞数量显著增加,同时成骨和血管生成情况也更好。研究还表明,用Ti2448合金预处理的巨噬细胞通过增加血小板衍生生长因子-BB(PDGF-BB)和骨形态发生蛋白-2(BMP-2)的分泌,显著促进了血管生成和成骨分化,并且增强了M2巨噬细胞的极化。我们推断,Ti2448通过Piezo1/YAP信号轴介导的巨噬细胞极化和相关细胞因子分泌来促进血管生成和成骨。这项研究可能有助于深入了解Ti2448的生物学特性,并为三维打印的Ti2448植入物未来在骨科手术中的应用提供有力的理论补充。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5fe5/8634253/42dc8dbd98e0/fcell-09-750948-g013.jpg

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