Cui Qun, Zheng Xiaona, Bai Yunyang, Guo Yaru, Liu Shuo, Lu Yanhui, Liu Lulu, Song Jia, Liu Yang, Heng Boon Chin, You Fuping, Xu Mingming, Deng Xuliang, Zhang Xuehui
Department of Dental Materials & Dental Medical Devices Testing Center, Peking University School and Hospital of Stomatology, Beijing, 100081, P. R. China.
Oral Translational Medicine Research Center, Joint Training base for Shanxi Provincial Key Laboratory in Oral and Maxillofacial Repair, Reconstruction and Regeneration, The First People's Hospital of Jinzhong, Jinzhong, Shanxi, 030600, P. R. China.
Adv Sci (Weinh). 2025 Feb;12(8):e2414278. doi: 10.1002/advs.202414278. Epub 2024 Dec 30.
Regulation of the immune response is key to promoting bone regeneration by electroactive biomaterials. However, how electrical signals at the micro- and nanoscale regulate the immune response and subsequent angiogenesis during bone regeneration remains to be elucidated. Here, the distinctly different surface potential distributions on charged poly(vinylidene fluoridetrifluoroethylene) (P(VDF-TrFE)) matrix surfaces are established by altering the dimensions of ferroelectric nanofillers from 0D BaTiO nanoparticles (homogeneous surface potential distribution, HOPD) to 1D BaTiO nanofibers (heterogeneous surface potential distribution, HEPD). Compared to HOPD, HEPD is significantly better at inducing the M2 polarization of macrophages and promoting neovascularization, which results in accelerated bone regeneration in vivo. The transcriptomic analysis reveals that macrophages modulated by HEPD display high expression levels of pro-angiogenic genes, which is corroborated by tube-formation assays, RT-qPCR, and western blot analyses in vitro. Mechanistic explorations elucidate activation of the PI3K-Akt signaling pathway, which in turn induces the polarization of macrophages toward a pro-angiogenic phenotype. This study elucidates the cascade of biological processes by which heterogeneous electrical signals at the micro- and nanoscale modulate macrophage functions to promote vascularization and bone regeneration. Hence, this study provides new insights into how the micro- and nanoscale distribution characteristics of electrical signals facilitate bone regeneration.
免疫反应的调节是电活性生物材料促进骨再生的关键。然而，在骨再生过程中，微米和纳米尺度的电信号如何调节免疫反应及随后的血管生成仍有待阐明。在此，通过将铁电纳米填料的尺寸从0D钛酸钡纳米颗粒（均匀表面电位分布，HOPD）改变为1D钛酸钡纳米纤维（异质表面电位分布，HEPD），在带电的聚偏氟乙烯-三氟乙烯（P(VDF-TrFE)）基质表面建立了明显不同的表面电位分布。与HOPD相比，HEPD在诱导巨噬细胞的M2极化和促进新血管形成方面明显更好，这导致体内骨再生加速。转录组分析表明，受HEPD调节的巨噬细胞显示出促血管生成基因的高表达水平，这在体外的管形成试验、RT-qPCR和蛋白质印迹分析中得到了证实。机制探索阐明了PI3K-Akt信号通路的激活，这反过来又诱导巨噬细胞向促血管生成表型极化。本研究阐明了微米和纳米尺度的异质电信号调节巨噬细胞功能以促进血管化和骨再生的生物过程级联。因此，本研究为电信号的微米和纳米尺度分布特征如何促进骨再生提供了新的见解。
