DataSheet1_Three-Dimensionally Printed Ti2448 With Low Stiffness Enhanced Angiogenesis and Osteogenesis by Regulating Macrophage Polarization via Piezo1/YAP Signaling Axis.zip

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 in vivo. However, these were not significant in a series of in vitro 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 in vivo. In vitro 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.

既往研究表明，相较于传统Ti6Al4V合金，新型低弹性模量Ti2448合金可显著降低应力遮挡效应，且更利于骨修复。本研究中，研究人员亦在体内实验中观察到三维打印Ti2448合金可促进成骨与血管生成，但该效应在一系列体外实验中并未显现出统计学显著性。已有研究表明，材料刚度可显著影响巨噬细胞的应答反应，而巨噬细胞介导的免疫调控直接决定骨植入物的预后。据此，本研究设计了更多实验，以探究三维打印Ti2448合金在巨噬细胞活化以及相关成骨、血管生成过程中的作用。正如预期，研究人员发现Ti2448合金植入物周围的M2型巨噬细胞（M2 macrophages）数量显著增加，体内成骨与血管生成效果亦更佳。体外实验结果同样显示，经Ti2448合金预处理的巨噬细胞可通过提升PDGF-BB与BMP-2的分泌量，显著促进血管生成与成骨分化，同时增强M2型巨噬细胞的极化水平。本研究推测，Ti2448合金可通过Piezo1/YAP信号轴介导的巨噬细胞极化及相关细胞因子分泌，促进血管生成与成骨分化。本研究可为阐明Ti2448合金的生物学特性提供新视角，同时为三维打印Ti2448合金植入物未来在骨科手术中的应用提供坚实的理论支撑。