2. Academic Validation
  3. Manipulation of Surface Potential Distribution Enhances Osteogenesis by Promoting Pro-Angiogenic Macrophage Polarization via Activation of the PI3K-Akt Signaling Pathway

Manipulation of Surface Potential Distribution Enhances Osteogenesis by Promoting Pro-Angiogenic Macrophage Polarization via Activation of the PI3K-Akt Signaling Pathway

  • Adv Sci (Weinh). 2024 Dec 30:e2414278. doi: 10.1002/advs.202414278.
Qun Cui 1,  Xiaona Zheng 1 2 3,  Yunyang Bai 4,  Yaru Guo 4,  Shuo Liu 1,  Yanhui Lu 1,  Lulu Liu 4,  Jia Song 1,  Yang Liu 1,  Boon Chin Heng 1,  Fuping You 5,  Mingming Xu 4,  Xuliang Deng 3 4,  Xuehui Zhang 1 2 3
Affiliations

Affiliations

  • 1 Department of Dental Materials & Dental Medical Devices Testing Center, Peking University School and Hospital of Stomatology, Beijing, 100081, P. R. China.
  • 2 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.
  • 3 National Engineering Research Center of Oral Biomaterials and Digital Medical Devices, NMPA Key Laboratory for Dental Materials, Beijing Laboratory of Biomedical Materials & Beijing Key Laboratory of Digital Stomatology, Peking University School and Hospital of Stomatology, Beijing, 100081, P. R. China.
  • 4 Department of Geriatric Dentistry, Peking University School and Hospital of Stomatology, Beijing, 100081, P. R. China.
  • 5 Institute of Systems Biomedicine, School of Basic Medical Sciences, NHC Key Laboratory of Medical Immunology, Beijing Key Laboratory of Tumor Systems Biology, Peking University Health Science Center, Beijing, 100191, P. R. China.
PMID: 39739591 DOI: 10.1002/advs.202414278
Abstract

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 BaTiO3 nanoparticles (homogeneous surface potential distribution, HOPD) to 1D BaTiO3 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.

Keywords

PI3K‐Akt signaling pathway; angiogenesis; bone regeneration; heterogeneous surface potential distribution; pro‐angiogenic macrophage polarization.

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