掺锶生物活性玻璃通过调控巨噬细胞极化促进成骨

Enhanced Osteogenesis of Strontium-substituted Bioactive Glasses through Regulation of Macrophage Polarization

巨噬细胞极化在骨修复中起着非常重要的作用。骨修复材料在植入体内后,会引起巨噬细胞的响应,使其向M1/M2极化,从而影响材料的成骨效果。本文制备了掺锶量分别为0%,5%,10%和15%摩尔百分比的锶掺杂微纳米生物活性玻璃(Sr-MNBG),并研究了不同掺锶量的Sr-MNBG对巨噬细胞极化的影响;随后,在此基础上研究了不同掺锶量Sr-MNBG调控的巨噬细胞分泌成分对小鼠骨髓间充质干细胞(m MSCs)向成骨分化的影响;最后,通过体内原位骨缺损修复实验验证了不同掺锶量Sr-MNBG对巨噬细胞极化的调控作用及其体内成骨作用。体外实验结果显示,掺锶量为5%,10%和15%的Sr-MNBG较掺锶量为0%的Sr-MNBG更能促进巨噬细胞向M2极化,其中10%掺锶量的Sr-MNBG具有最强的促巨噬细胞M2极化作用,且10%掺锶量的Sr-MNBG调控的巨噬细胞分泌成分更有利于成骨。体内实验结果表明,不同掺锶量的Sr-MNBG植入到体内后,10%掺锶量的Sr-MNBG周围有更多的M2巨噬细胞浸润,且表现出更好的骨修复效果,与体外实验结果相一致。因此,Sr-MNBG有望作为一种富有前景的免疫调控材料应用于骨修复。

Macrophage polarization plays an important role in bone repair. Once being implanted in the body, bone re- pair materials will trigger response of macrophage, making it switch to M1/M2 phenotype, thus affect the osteogenic effect of the material. In this work, Strontium-substituted micro/nano bioactive glasses （Sr-MNBG）with 0, 5% , 10% and 15% molar percent of strontium element were prepared, and the effect of Sr-MNBG on macrophage polarization was studied. Subsequently, the effects of Sr-MNBG with different strontimn incorporation ratio on the osteogenic differentia-tion of murine bone marrow mesenchymal stem cells （mMSCs） were evaluated. Finally, the in vivo assessment was con- ducted to verify- the polarization of macrophage and osteogenesis of Sr-MNBG through in situ bone defect repair experi- ment. The in vitro results showed that compared with 0% Sr-MNBG,Sr-MNBG with 5% , 10% and 15% molar percent of strontium element could further promote macrophage polarization toward M2, and 10% Sr-MNBG displayed the best effect. Moreover, the secretion of macrophages modulated by 10% Sr-MNBG was more beneficial to osteogenesis. The in vivo results showed that there were more M2 macrophages around 10% Sr-MNBG after implantation in the body, and bet- ter bone repair effect was found in the 10% Sr-MNBG group, which were consistent with the in vitro results. Therefore, Sr-MNBG is expected to be a promising immunoregulatory material for bone repair.