Neodymium-doped mesoporous silica nanoparticles promote bone regeneration via autophagy-mediated macrophage immunomodulation
Rare earth nanomaterials, especially those incorporating neodymium, hold great potential for bone regeneration, but their clinical application is limited by insufficient understanding of immunomodulatory effects and potential toxicity concerns. To address this, we developed neodymium-doped mesoporou...
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Elsevier
2025-10-01
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| Series: | Materials Today Bio |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2590006425007689 |
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| author | Qing Zhang Duraipandy Natarajan Weijian Gao Haokun He Shuguang Cheng Yin Xiao Marco N. Helder Sujuan Zeng Richard T. Jaspers Janak Lal Pathak |
| author_facet | Qing Zhang Duraipandy Natarajan Weijian Gao Haokun He Shuguang Cheng Yin Xiao Marco N. Helder Sujuan Zeng Richard T. Jaspers Janak Lal Pathak |
| author_sort | Qing Zhang |
| collection | DOAJ |
| description | Rare earth nanomaterials, especially those incorporating neodymium, hold great potential for bone regeneration, but their clinical application is limited by insufficient understanding of immunomodulatory effects and potential toxicity concerns. To address this, we developed neodymium-doped mesoporous silica nanoparticles (NDMSN) to modulate macrophage autophagy and polarization. NDMSN exhibited uniform dispersion with an average size of 103 nm. NDMSN displayed low cytotoxicity in M0 macrophages and effectively suppressed pro-inflammatory responses in M1 macrophages. This was evidenced by the inhibition of pro-inflammatory markers (IL-6, IL-1β, and iNOS) and the promotion of anti-inflammatory markers (IL-4, IL-10, and CD206). Autophagy activation was confirmed by upregulated expression of P62, LC3A, BECLIN1, and ATG7, and the anti-inflammatory effects were attenuated upon autophagy inhibition with 3-methyladenine, highlighting autophagy's essential role. Conditioned medium from NDMSN-treated M1 macrophages exhibited pro-angiogenic activity in human umbilical vein endothelial cells by enhancing tube formation and elevating angiogenic gene expression, while showing pro-osteogenic potential in mouse bone marrow mesenchymal stromal cells. In vivo, NDMSN mitigated LPS-induced bone destruction in a mouse calvarial osteolysis model and suppressed osteoclast differentiation. Its osteogenic capacity was further validated in a zebrafish calvarial defect model. These findings demonstrate that NDMSN is a promising immunomodulatory and osteogenic nanomaterial, offering a novel therapeutic strategy for bone regeneration. |
| format | Article |
| id | doaj-art-0f8e28d455cf41049e1dea0cfd624f66 |
| institution | Kabale University |
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| language | English |
| publishDate | 2025-10-01 |
| publisher | Elsevier |
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| series | Materials Today Bio |
| spelling | doaj-art-0f8e28d455cf41049e1dea0cfd624f662025-08-20T03:43:44ZengElsevierMaterials Today Bio2590-00642025-10-013410219810.1016/j.mtbio.2025.102198Neodymium-doped mesoporous silica nanoparticles promote bone regeneration via autophagy-mediated macrophage immunomodulationQing Zhang0Duraipandy Natarajan1Weijian Gao2Haokun He3Shuguang Cheng4Yin Xiao5Marco N. Helder6Sujuan Zeng7Richard T. Jaspers8Janak Lal Pathak9School and Hospital of Stomatology, Guangdong Engineering Research Center of Oral Restoration and Reconstruction, Guangzhou Key Laboratory of Basic and Applied Research of Oral Regenerative Medicine, Guangzhou Medical University, Guangzhou, 510182, China; Laboratory for Myology, Department of Human Movement Sciences, Faculty of Behavioural and Movement Sciences, Vrije Universiteit Amsterdam, Amsterdam Movement Sciences, 1081 BT, Amsterdam, the NetherlandsSchool and Hospital of Stomatology, Guangdong Engineering Research Center of Oral Restoration and Reconstruction, Guangzhou Key Laboratory of Basic and Applied Research of Oral Regenerative Medicine, Guangzhou Medical University, Guangzhou, 510182, ChinaSchool of Biomedical Engineering, Guangzhou Medical University, Guangzhou, 511436, Guangdong, ChinaSchool and Hospital of Stomatology, Guangdong Engineering Research Center of Oral Restoration and Reconstruction, Guangzhou Key Laboratory of Basic and Applied Research of Oral Regenerative Medicine, Guangzhou Medical University, Guangzhou, 510182, ChinaSchool and Hospital of Stomatology, Guangdong Engineering Research Center of Oral Restoration and Reconstruction, Guangzhou Key Laboratory of Basic and Applied Research of Oral Regenerative Medicine, Guangzhou Medical University, Guangzhou, 510182, ChinaSchool and Hospital of Stomatology, Guangdong Engineering Research Center of Oral Restoration and Reconstruction, Guangzhou Key Laboratory of Basic and Applied Research of Oral Regenerative Medicine, Guangzhou Medical University, Guangzhou, 510182, China; School of Medicine and Dentistry & Institute for Biomedicine and Glycomics, Griffith University, Gold Coast, QLD, 4222, AustraliaDepartment of Oral and Maxillofacial Surgery/Oral Pathology, Amsterdam University Medical Centers and Academic Centre for Dentistry Amsterdam (ACTA), Vrije Universiteit Amsterdam, Amsterdam Movement Sciences, 1081 HV, Amsterdam, the NetherlandsSchool and Hospital of Stomatology, Guangdong Engineering Research Center of Oral Restoration and Reconstruction, Guangzhou Key Laboratory of Basic and Applied Research of Oral Regenerative Medicine, Guangzhou Medical University, Guangzhou, 510182, China; Corresponding author. School and Hospital of Stomatology, Guangdong Engineering Research Center of Oral Restoration and Reconstruction, Guangzhou Key Laboratory of Basic and Applied Research of Oral Regenerative Medicine, Guangzhou Medical University, Guangzhou, 510182, China.School and Hospital of Stomatology, Guangdong Engineering Research Center of Oral Restoration and Reconstruction, Guangzhou Key Laboratory of Basic and Applied Research of Oral Regenerative Medicine, Guangzhou Medical University, Guangzhou, 510182, China; Laboratory for Myology, Department of Human Movement Sciences, Faculty of Behavioural and Movement Sciences, Vrije Universiteit Amsterdam, Amsterdam Movement Sciences, 1081 BT, Amsterdam, the Netherlands; Corresponding author. Laboratory for Myology, Department of Human Movement Sciences, Faculty of Behavioural and Movement Sciences, Vrije Universiteit Amsterdam, Amsterdam Movement Sciences, 1081 BT, Amsterdam, the NetherlandsSchool and Hospital of Stomatology, Guangdong Engineering Research Center of Oral Restoration and Reconstruction, Guangzhou Key Laboratory of Basic and Applied Research of Oral Regenerative Medicine, Guangzhou Medical University, Guangzhou, 510182, China; Corresponding author. School and Hospital of Stomatology, Guangdong Engineering Research Center of Oral Restoration and Reconstruction, Guangzhou Key Laboratory of Basic and Applied Research of Oral Regenerative Medicine, Guangzhou Medical University, Guangzhou, 510182, China.Rare earth nanomaterials, especially those incorporating neodymium, hold great potential for bone regeneration, but their clinical application is limited by insufficient understanding of immunomodulatory effects and potential toxicity concerns. To address this, we developed neodymium-doped mesoporous silica nanoparticles (NDMSN) to modulate macrophage autophagy and polarization. NDMSN exhibited uniform dispersion with an average size of 103 nm. NDMSN displayed low cytotoxicity in M0 macrophages and effectively suppressed pro-inflammatory responses in M1 macrophages. This was evidenced by the inhibition of pro-inflammatory markers (IL-6, IL-1β, and iNOS) and the promotion of anti-inflammatory markers (IL-4, IL-10, and CD206). Autophagy activation was confirmed by upregulated expression of P62, LC3A, BECLIN1, and ATG7, and the anti-inflammatory effects were attenuated upon autophagy inhibition with 3-methyladenine, highlighting autophagy's essential role. Conditioned medium from NDMSN-treated M1 macrophages exhibited pro-angiogenic activity in human umbilical vein endothelial cells by enhancing tube formation and elevating angiogenic gene expression, while showing pro-osteogenic potential in mouse bone marrow mesenchymal stromal cells. In vivo, NDMSN mitigated LPS-induced bone destruction in a mouse calvarial osteolysis model and suppressed osteoclast differentiation. Its osteogenic capacity was further validated in a zebrafish calvarial defect model. These findings demonstrate that NDMSN is a promising immunomodulatory and osteogenic nanomaterial, offering a novel therapeutic strategy for bone regeneration.http://www.sciencedirect.com/science/article/pii/S2590006425007689Neodymium doped mesoporous silica nanoparticlesImmunomodulationAutophagyAngiogenesisOsteogenesisOsteolysis |
| spellingShingle | Qing Zhang Duraipandy Natarajan Weijian Gao Haokun He Shuguang Cheng Yin Xiao Marco N. Helder Sujuan Zeng Richard T. Jaspers Janak Lal Pathak Neodymium-doped mesoporous silica nanoparticles promote bone regeneration via autophagy-mediated macrophage immunomodulation Materials Today Bio Neodymium doped mesoporous silica nanoparticles Immunomodulation Autophagy Angiogenesis Osteogenesis Osteolysis |
| title | Neodymium-doped mesoporous silica nanoparticles promote bone regeneration via autophagy-mediated macrophage immunomodulation |
| title_full | Neodymium-doped mesoporous silica nanoparticles promote bone regeneration via autophagy-mediated macrophage immunomodulation |
| title_fullStr | Neodymium-doped mesoporous silica nanoparticles promote bone regeneration via autophagy-mediated macrophage immunomodulation |
| title_full_unstemmed | Neodymium-doped mesoporous silica nanoparticles promote bone regeneration via autophagy-mediated macrophage immunomodulation |
| title_short | Neodymium-doped mesoporous silica nanoparticles promote bone regeneration via autophagy-mediated macrophage immunomodulation |
| title_sort | neodymium doped mesoporous silica nanoparticles promote bone regeneration via autophagy mediated macrophage immunomodulation |
| topic | Neodymium doped mesoporous silica nanoparticles Immunomodulation Autophagy Angiogenesis Osteogenesis Osteolysis |
| url | http://www.sciencedirect.com/science/article/pii/S2590006425007689 |
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