Manipulation of Surface Potential Distribution Enhances Osteogenesis by Promoting Pro‐Angiogenic Macrophage Polarization via Activation of the PI3K‐Akt Signaling Pathway
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...
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Wiley
2025-02-01
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| Series: | Advanced Science |
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| Online Access: | https://doi.org/10.1002/advs.202414278 |
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| author | Qun Cui Xiaona Zheng Yunyang Bai Yaru Guo Shuo Liu Yanhui Lu Lulu Liu Jia Song Yang Liu Boon Chin Heng Fuping You Mingming Xu Xuliang Deng Xuehui Zhang |
| author_facet | Qun Cui Xiaona Zheng Yunyang Bai Yaru Guo Shuo Liu Yanhui Lu Lulu Liu Jia Song Yang Liu Boon Chin Heng Fuping You Mingming Xu Xuliang Deng Xuehui Zhang |
| author_sort | Qun Cui |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-25ef520fcf864b2d9418a7f7d5b70bf1 |
| institution | OA Journals |
| issn | 2198-3844 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | Wiley |
| record_format | Article |
| series | Advanced Science |
| spelling | doaj-art-25ef520fcf864b2d9418a7f7d5b70bf12025-08-20T01:51:47ZengWileyAdvanced Science2198-38442025-02-01128n/an/a10.1002/advs.202414278Manipulation of Surface Potential Distribution Enhances Osteogenesis by Promoting Pro‐Angiogenic Macrophage Polarization via Activation of the PI3K‐Akt Signaling PathwayQun Cui0Xiaona Zheng1Yunyang Bai2Yaru Guo3Shuo Liu4Yanhui Lu5Lulu Liu6Jia Song7Yang Liu8Boon Chin Heng9Fuping You10Mingming Xu11Xuliang Deng12Xuehui Zhang13Department of Dental Materials & Dental Medical Devices Testing Center Peking University School and Hospital of Stomatology Beijing 100081 P. R. ChinaDepartment of Dental Materials & Dental Medical Devices Testing Center Peking University School and Hospital of Stomatology Beijing 100081 P. R. ChinaDepartment of Geriatric Dentistry Peking University School and Hospital of Stomatology Beijing 100081 P. R. ChinaDepartment of Geriatric Dentistry Peking University School and Hospital of Stomatology Beijing 100081 P. R. ChinaDepartment of Dental Materials & Dental Medical Devices Testing Center Peking University School and Hospital of Stomatology Beijing 100081 P. R. ChinaDepartment of Dental Materials & Dental Medical Devices Testing Center Peking University School and Hospital of Stomatology Beijing 100081 P. R. ChinaDepartment of Geriatric Dentistry Peking University School and Hospital of Stomatology Beijing 100081 P. R. ChinaDepartment of Dental Materials & Dental Medical Devices Testing Center Peking University School and Hospital of Stomatology Beijing 100081 P. R. ChinaDepartment of Dental Materials & Dental Medical Devices Testing Center Peking University School and Hospital of Stomatology Beijing 100081 P. R. ChinaDepartment of Dental Materials & Dental Medical Devices Testing Center Peking University School and Hospital of Stomatology Beijing 100081 P. R. ChinaInstitute 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. ChinaDepartment of Geriatric Dentistry Peking University School and Hospital of Stomatology Beijing 100081 P. R. ChinaDepartment of Geriatric Dentistry Peking University School and Hospital of Stomatology Beijing 100081 P. R. ChinaDepartment of Dental Materials & Dental Medical Devices Testing Center Peking University School and Hospital of Stomatology Beijing 100081 P. R. ChinaAbstract 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.https://doi.org/10.1002/advs.202414278angiogenesisbone regenerationheterogeneous surface potential distributionPI3K‐Akt signaling pathwaypro‐angiogenic macrophage polarization |
| spellingShingle | Qun Cui Xiaona Zheng Yunyang Bai Yaru Guo Shuo Liu Yanhui Lu Lulu Liu Jia Song Yang Liu Boon Chin Heng Fuping You Mingming Xu Xuliang Deng Xuehui Zhang Manipulation of Surface Potential Distribution Enhances Osteogenesis by Promoting Pro‐Angiogenic Macrophage Polarization via Activation of the PI3K‐Akt Signaling Pathway Advanced Science angiogenesis bone regeneration heterogeneous surface potential distribution PI3K‐Akt signaling pathway pro‐angiogenic macrophage polarization |
| title | Manipulation of Surface Potential Distribution Enhances Osteogenesis by Promoting Pro‐Angiogenic Macrophage Polarization via Activation of the PI3K‐Akt Signaling Pathway |
| title_full | Manipulation of Surface Potential Distribution Enhances Osteogenesis by Promoting Pro‐Angiogenic Macrophage Polarization via Activation of the PI3K‐Akt Signaling Pathway |
| title_fullStr | Manipulation of Surface Potential Distribution Enhances Osteogenesis by Promoting Pro‐Angiogenic Macrophage Polarization via Activation of the PI3K‐Akt Signaling Pathway |
| title_full_unstemmed | Manipulation of Surface Potential Distribution Enhances Osteogenesis by Promoting Pro‐Angiogenic Macrophage Polarization via Activation of the PI3K‐Akt Signaling Pathway |
| title_short | Manipulation of Surface Potential Distribution Enhances Osteogenesis by Promoting Pro‐Angiogenic Macrophage Polarization via Activation of the PI3K‐Akt Signaling Pathway |
| title_sort | manipulation of surface potential distribution enhances osteogenesis by promoting pro angiogenic macrophage polarization via activation of the pi3k akt signaling pathway |
| topic | angiogenesis bone regeneration heterogeneous surface potential distribution PI3K‐Akt signaling pathway pro‐angiogenic macrophage polarization |
| url | https://doi.org/10.1002/advs.202414278 |
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