Hydrogel loaded with cerium-manganese nanoparticles and nerve growth factor enhances spinal cord injury repair by modulating immune microenvironment and promoting neuronal regeneration
Abstract Background Spinal cord injury (SCI) treatment remains a formidable challenge, as current therapeutic approaches provide only marginal relief and fail to reverse the underlying tissue damage. This study aims to develop a novel composite material combining enzymatic nanoparticles and nerve gr...
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| Format: | Article |
| Language: | English |
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BMC
2025-01-01
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| Series: | Journal of Nanobiotechnology |
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| Online Access: | https://doi.org/10.1186/s12951-025-03098-3 |
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| author | Zhaoyang Gong Zhenhao Chen Dachuan Li Xiao Lu Jianwei Wu Hanqiu Sun Ximeng Wang Siyang Liu Xinlei Xia Feizhou Lu Jianyuan Jiang Chi Sun Hongli Wang Feng Zeng Xiaosheng Ma |
| author_facet | Zhaoyang Gong Zhenhao Chen Dachuan Li Xiao Lu Jianwei Wu Hanqiu Sun Ximeng Wang Siyang Liu Xinlei Xia Feizhou Lu Jianyuan Jiang Chi Sun Hongli Wang Feng Zeng Xiaosheng Ma |
| author_sort | Zhaoyang Gong |
| collection | DOAJ |
| description | Abstract Background Spinal cord injury (SCI) treatment remains a formidable challenge, as current therapeutic approaches provide only marginal relief and fail to reverse the underlying tissue damage. This study aims to develop a novel composite material combining enzymatic nanoparticles and nerve growth factor (NGF) to modulate the immune microenvironment and enhance SCI repair. Methods CeMn nanoparticles (NP) and CeMn NP-polyethylene glycol (PEG) nanozymes were synthesized via sol–gel reaction and DSPE-mPEG modification. Transmission Electron Microscopy, Selected-Area Electron Diffraction, X-ray Diffraction and X-ray Photoelectron Spectroscopy confirmed their crystalline structure, mixed-valence states, and redox properties. Size uniformity, biocompatibility, and catalytic activity were assessed via hydrodynamic diameter, zeta potential, and elemental analysis. The Lightgel/NGF/CeMn NP-PEG composite was synthesized and characterized via electron microscopy, compression testing, rheological analysis, NGF release kinetics, and 30-day degradation studies. Both in vitro and in vivo experiments were conducted to evaluate the therapeutic effects of the composite on SCI. Results The Lightgel/NGF/CeMn NP-PEG composite was successfully synthesized, exhibiting favorable physical properties. At a CeMn NP-PEG concentration of 4 µg/mL, the composite maintained cell viability and demonstrated enhanced biological activity. It also showed superior mechanical properties and an effective NGF release profile. Notably, the composite significantly upregulated the expression of nerve growth-associated proteins, reduced inflammatory cytokines, scavenged reactive oxygen species (ROS), and promoted M2 macrophage polarization by inhibiting the cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) signaling pathway. In a rat SCI model, it facilitated functional recovery and attenuated inflammation. Conclusion The Lightgel/NGF/CeMn NP-PEG composite shows significant therapeutic promise for SCI, effectively eliminating ROS, promoting M2 macrophage polarization, reducing pro-inflammatory cytokines, and supporting neuronal regeneration. These effects substantially enhance motor function in SCI rats, positioning it as a promising candidate for future clinical applications. Graphical Abstract |
| format | Article |
| id | doaj-art-4acaf9d87c394b1d987b30f010ace8c5 |
| institution | Kabale University |
| issn | 1477-3155 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Nanobiotechnology |
| spelling | doaj-art-4acaf9d87c394b1d987b30f010ace8c52025-01-26T12:50:57ZengBMCJournal of Nanobiotechnology1477-31552025-01-0123112310.1186/s12951-025-03098-3Hydrogel loaded with cerium-manganese nanoparticles and nerve growth factor enhances spinal cord injury repair by modulating immune microenvironment and promoting neuronal regenerationZhaoyang Gong0Zhenhao Chen1Dachuan Li2Xiao Lu3Jianwei Wu4Hanqiu Sun5Ximeng Wang6Siyang Liu7Xinlei Xia8Feizhou Lu9Jianyuan Jiang10Chi Sun11Hongli Wang12Feng Zeng13Xiaosheng Ma14Department of Orthopedics, Huashan Hospital, Fudan UniversityDepartment of Orthopedics, Huashan Hospital, Fudan UniversityDepartment of Orthopedics, Huashan Hospital, Fudan UniversityDepartment of Orthopedics, Huashan Hospital, Fudan UniversityDepartment of Orthopedics, Huashan Hospital, Fudan UniversityDepartment of Orthopedics, Huashan Hospital, Fudan UniversityDepartment of Orthopedics, Huashan Hospital, Fudan UniversityDepartment of Orthopedics, Huashan Hospital, Fudan UniversityDepartment of Orthopedics, Huashan Hospital, Fudan UniversityDepartment of Orthopedics, Huashan Hospital, Fudan UniversityDepartment of Orthopedics, Huashan Hospital, Fudan UniversityDepartment of Orthopedics, Huashan Hospital, Fudan UniversityDepartment of Orthopedics, Huashan Hospital, Fudan UniversityArtemisinin Research Center, Institute of Science and Technology, The First Affiliated Hospital, The First Clinical Medical School, Lingnan Medical Research Center, Guangzhou University of Chinese MedicineDepartment of Orthopedics, Huashan Hospital, Fudan UniversityAbstract Background Spinal cord injury (SCI) treatment remains a formidable challenge, as current therapeutic approaches provide only marginal relief and fail to reverse the underlying tissue damage. This study aims to develop a novel composite material combining enzymatic nanoparticles and nerve growth factor (NGF) to modulate the immune microenvironment and enhance SCI repair. Methods CeMn nanoparticles (NP) and CeMn NP-polyethylene glycol (PEG) nanozymes were synthesized via sol–gel reaction and DSPE-mPEG modification. Transmission Electron Microscopy, Selected-Area Electron Diffraction, X-ray Diffraction and X-ray Photoelectron Spectroscopy confirmed their crystalline structure, mixed-valence states, and redox properties. Size uniformity, biocompatibility, and catalytic activity were assessed via hydrodynamic diameter, zeta potential, and elemental analysis. The Lightgel/NGF/CeMn NP-PEG composite was synthesized and characterized via electron microscopy, compression testing, rheological analysis, NGF release kinetics, and 30-day degradation studies. Both in vitro and in vivo experiments were conducted to evaluate the therapeutic effects of the composite on SCI. Results The Lightgel/NGF/CeMn NP-PEG composite was successfully synthesized, exhibiting favorable physical properties. At a CeMn NP-PEG concentration of 4 µg/mL, the composite maintained cell viability and demonstrated enhanced biological activity. It also showed superior mechanical properties and an effective NGF release profile. Notably, the composite significantly upregulated the expression of nerve growth-associated proteins, reduced inflammatory cytokines, scavenged reactive oxygen species (ROS), and promoted M2 macrophage polarization by inhibiting the cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) signaling pathway. In a rat SCI model, it facilitated functional recovery and attenuated inflammation. Conclusion The Lightgel/NGF/CeMn NP-PEG composite shows significant therapeutic promise for SCI, effectively eliminating ROS, promoting M2 macrophage polarization, reducing pro-inflammatory cytokines, and supporting neuronal regeneration. These effects substantially enhance motor function in SCI rats, positioning it as a promising candidate for future clinical applications. Graphical Abstracthttps://doi.org/10.1186/s12951-025-03098-3Spinal cord injuryCerium-manganese nanoparticlesNerve growth factorHydrogelsInflammationReactive oxygen species |
| spellingShingle | Zhaoyang Gong Zhenhao Chen Dachuan Li Xiao Lu Jianwei Wu Hanqiu Sun Ximeng Wang Siyang Liu Xinlei Xia Feizhou Lu Jianyuan Jiang Chi Sun Hongli Wang Feng Zeng Xiaosheng Ma Hydrogel loaded with cerium-manganese nanoparticles and nerve growth factor enhances spinal cord injury repair by modulating immune microenvironment and promoting neuronal regeneration Journal of Nanobiotechnology Spinal cord injury Cerium-manganese nanoparticles Nerve growth factor Hydrogels Inflammation Reactive oxygen species |
| title | Hydrogel loaded with cerium-manganese nanoparticles and nerve growth factor enhances spinal cord injury repair by modulating immune microenvironment and promoting neuronal regeneration |
| title_full | Hydrogel loaded with cerium-manganese nanoparticles and nerve growth factor enhances spinal cord injury repair by modulating immune microenvironment and promoting neuronal regeneration |
| title_fullStr | Hydrogel loaded with cerium-manganese nanoparticles and nerve growth factor enhances spinal cord injury repair by modulating immune microenvironment and promoting neuronal regeneration |
| title_full_unstemmed | Hydrogel loaded with cerium-manganese nanoparticles and nerve growth factor enhances spinal cord injury repair by modulating immune microenvironment and promoting neuronal regeneration |
| title_short | Hydrogel loaded with cerium-manganese nanoparticles and nerve growth factor enhances spinal cord injury repair by modulating immune microenvironment and promoting neuronal regeneration |
| title_sort | hydrogel loaded with cerium manganese nanoparticles and nerve growth factor enhances spinal cord injury repair by modulating immune microenvironment and promoting neuronal regeneration |
| topic | Spinal cord injury Cerium-manganese nanoparticles Nerve growth factor Hydrogels Inflammation Reactive oxygen species |
| url | https://doi.org/10.1186/s12951-025-03098-3 |
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