An injectable multifunctional nanocomposite hydrogel promotes vascularized bone regeneration by regulating macrophages
Abstract The local inflammatory microenvironment, insufficient vascularization, and inadequate bone repair materials are the three key factors that constrain the repair of bone defects. Here, we synthesized a composite nanoparticle, TPQ (TCP-PDA-QK), with a core‒shell structure. The core consists of...
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BMC
2025-04-01
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| Series: | Journal of Nanobiotechnology |
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| Online Access: | https://doi.org/10.1186/s12951-025-03358-2 |
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| author | Huaiyuan Zhang Yu Wang Wenyu Qiao Xueneng Hu Huifen Qiang Kuo Xia Longhai Du Luling Yang Yi Bao Jie Gao Tinglin Zhang Zuochong Yu |
| author_facet | Huaiyuan Zhang Yu Wang Wenyu Qiao Xueneng Hu Huifen Qiang Kuo Xia Longhai Du Luling Yang Yi Bao Jie Gao Tinglin Zhang Zuochong Yu |
| author_sort | Huaiyuan Zhang |
| collection | DOAJ |
| description | Abstract The local inflammatory microenvironment, insufficient vascularization, and inadequate bone repair materials are the three key factors that constrain the repair of bone defects. Here, we synthesized a composite nanoparticle, TPQ (TCP-PDA-QK), with a core‒shell structure. The core consists of nanotricalcium phosphate (TCP), and the shell is derived from polydopamine (PDA). The surface of the shell is modified with a vascular endothelial growth factor (VEGF) mimic peptide (QK peptide). TPQ was then embedded in porous methacrylate gelatin (GelMA) to form a TPQGel hydrogel. In the inflammatory environment, the TPQGel hydrogel can gradually release drugs through pH responsiveness, promoting M2 macrophage polarization, vascularization and bone regeneration in turn. In addition, reprogrammed M2 macrophages stimulate the generation of anti-inflammatory and pro-healing growth factors, which provide additional support for angiogenesis and bone regeneration. The TPQGel hydrogel can not only accurately fill irregular bone defects but also has excellent biocompatibility, making it highly suitable for the minimally invasive treatment of bone defects. Transcriptomic tests revealed that the TPQGel hydrogel achieved macrophage reprogramming by regulating the PI3K-AKT signalling pathway. Overall, the TPQGel hydrogel can be harnessed for safe and efficient therapeutics that accelerate the repair of bone defects. Graphical Abstract |
| format | Article |
| id | doaj-art-4e01cc0ecf4b490c9145759f03c8cd26 |
| institution | OA Journals |
| issn | 1477-3155 |
| language | English |
| publishDate | 2025-04-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Nanobiotechnology |
| spelling | doaj-art-4e01cc0ecf4b490c9145759f03c8cd262025-08-20T02:28:04ZengBMCJournal of Nanobiotechnology1477-31552025-04-0123112410.1186/s12951-025-03358-2An injectable multifunctional nanocomposite hydrogel promotes vascularized bone regeneration by regulating macrophagesHuaiyuan Zhang0Yu Wang1Wenyu Qiao2Xueneng Hu3Huifen Qiang4Kuo Xia5Longhai Du6Luling Yang7Yi Bao8Jie Gao9Tinglin Zhang10Zuochong Yu11Department of Orthopedics, Jinshan Hospital, Fudan UniversityDepartment of Orthopedics, Jinshan Hospital, Fudan UniversityDepartment of General Surgery, Jinshan Hospital, Fudan UniversityDepartment of Orthopedics, Jinshan Hospital, Fudan UniversityChanghai Clinical Research Unit, Shanghai Changhai Hospital, Naval Medical UniversityDepartment of Orthopedics, Jinshan Hospital, Fudan UniversityDepartment of Orthopedics, Jinshan Hospital, Fudan UniversityDigestive Endoscopy Center, School of Medicine, Shanghai Tongren Hospital, Shanghai Jiao Tong UniversityBiological Safety Protection 3-Level Laboratory, Guangxi Medical UniversityChanghai Clinical Research Unit, Shanghai Changhai Hospital, Naval Medical UniversityChanghai Clinical Research Unit, Shanghai Changhai Hospital, Naval Medical UniversityDepartment of Orthopedics, Jinshan Hospital, Fudan UniversityAbstract The local inflammatory microenvironment, insufficient vascularization, and inadequate bone repair materials are the three key factors that constrain the repair of bone defects. Here, we synthesized a composite nanoparticle, TPQ (TCP-PDA-QK), with a core‒shell structure. The core consists of nanotricalcium phosphate (TCP), and the shell is derived from polydopamine (PDA). The surface of the shell is modified with a vascular endothelial growth factor (VEGF) mimic peptide (QK peptide). TPQ was then embedded in porous methacrylate gelatin (GelMA) to form a TPQGel hydrogel. In the inflammatory environment, the TPQGel hydrogel can gradually release drugs through pH responsiveness, promoting M2 macrophage polarization, vascularization and bone regeneration in turn. In addition, reprogrammed M2 macrophages stimulate the generation of anti-inflammatory and pro-healing growth factors, which provide additional support for angiogenesis and bone regeneration. The TPQGel hydrogel can not only accurately fill irregular bone defects but also has excellent biocompatibility, making it highly suitable for the minimally invasive treatment of bone defects. Transcriptomic tests revealed that the TPQGel hydrogel achieved macrophage reprogramming by regulating the PI3K-AKT signalling pathway. Overall, the TPQGel hydrogel can be harnessed for safe and efficient therapeutics that accelerate the repair of bone defects. Graphical Abstracthttps://doi.org/10.1186/s12951-025-03358-2Inflammatory microenvironmentBone defectsCore‒shell structureM2 macrophage polarizationVascularizationBone regeneration |
| spellingShingle | Huaiyuan Zhang Yu Wang Wenyu Qiao Xueneng Hu Huifen Qiang Kuo Xia Longhai Du Luling Yang Yi Bao Jie Gao Tinglin Zhang Zuochong Yu An injectable multifunctional nanocomposite hydrogel promotes vascularized bone regeneration by regulating macrophages Journal of Nanobiotechnology Inflammatory microenvironment Bone defects Core‒shell structure M2 macrophage polarization Vascularization Bone regeneration |
| title | An injectable multifunctional nanocomposite hydrogel promotes vascularized bone regeneration by regulating macrophages |
| title_full | An injectable multifunctional nanocomposite hydrogel promotes vascularized bone regeneration by regulating macrophages |
| title_fullStr | An injectable multifunctional nanocomposite hydrogel promotes vascularized bone regeneration by regulating macrophages |
| title_full_unstemmed | An injectable multifunctional nanocomposite hydrogel promotes vascularized bone regeneration by regulating macrophages |
| title_short | An injectable multifunctional nanocomposite hydrogel promotes vascularized bone regeneration by regulating macrophages |
| title_sort | injectable multifunctional nanocomposite hydrogel promotes vascularized bone regeneration by regulating macrophages |
| topic | Inflammatory microenvironment Bone defects Core‒shell structure M2 macrophage polarization Vascularization Bone regeneration |
| url | https://doi.org/10.1186/s12951-025-03358-2 |
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