A vessel subtype beneficial for osteogenesis enhanced by strontium-doped sodium titanate nanorods by modulating macrophage polarization
A vessel subtype beneficial for osteogenesis enhanced by strontium-doped sodium titanate nanorods by modulating macrophage polarization
复制标题
掺锶钛酸钠纳米棒通过调节巨噬细胞极化增强有利于成骨的血管亚型
DOI：
10.1039/d0tb00282h
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发表时间：
2020-07-28
影响因子：
7
通讯作者：
Guo, Zheng
中科院分区：
文献类型：
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作者：
Guo, Shuo;Yu, Dongmei;Guo, Zheng
早期血管化在骨愈合中起重要作用，尤其是在界面骨形成中。已经对钛表面进行了许多修饰以促进血管生成。此外，据报道，成骨细胞分泌的细胞因子可增强早期血管生成，然而，由于成骨细胞在炎症消退后出现，因此效果有限。我们制备了一种新的由锶离子负载的钛酸钠纳米棒（STSr）组成的缓释系统，并研究了其通过调节巨噬细胞亚型对血管生成的影响。在体外研究中，STSr通过调节M1巨噬细胞向M2巨噬细胞的转化，显著促进血管生成和CD31（hi）Emcn（hi）血管的形成。在STSr表面孵育后，巨噬细胞（RAW264.7）向M2亚型极化，并表达高水平的PDGF-BB。RAW264.7细胞的条件培养液可促进HUVECs的小管形成、迁移和向成骨血管（CD31（hi）Emcn（hi）血管）分化。体内研究显示植入物周围的CD31（hi）Emcn（hi）表达水平较高。随着血管化的增强，骨形成和骨整合得到改善。我们的研究为在钛上制造的新型功能性形貌表面的临床应用奠定了基础，这些表面可以应用于新的骨科植入物，以改善患者的预后。
Early vascularization plays an important role in bone healing, especially in interfacial bone formation. Many modifications have been made to titanium surfaces to promote angiogenesis. In addition, cytokines secreted by osteoblasts have been reported to enhance early angiogenesis, however, the effect is limited because osteoblasts arise after inflammation subsides. We fabricated a newly sustained release system consisting of Sr ion-loaded sodium titanate nanorods (STSr) and studied its effect on angiogenesis by regulating macrophage subtypes. In an in vitro study, STSr significantly promoted the angiogenesis and formation of CD31(hi)Emcn(hi) vessels by modulating the transformation of M1 macrophages toward M2 macrophages. After incubation on STSr surfaces, macrophages (RAW264.7) polarized toward M2 subtypes and expressed high levels of PDGF-BB. Furthermore, the conditioned medium from RAW264.7 cells enhanced the ability of tubule formation and migration of HUVECs and their differentiation into pro-osteogenesis vessels (CD31(hi)Emcn(hi) vessels). In vivo studies showed high expression levels of CD31(hi)Emcn(hi) surrounding implants. Accompanied with enhanced vascularization, improved bone formation and osseointegration were observed. Our study serves as a basis for the clinical application of novel functional topography surfaces fabricated on titanium, which can be applied in new orthopedic implants for the better prognosis of patients.