Silicon Enhances Functional Mitochondrial Transfer to Improve Neurovascularization in Diabetic Bone Regeneration
Abstract Diabetes mellitus is a metabolic disorder associated with an increased risk of fractures and delayed fracture healing, leading to a higher prevalence of bone defects. Recent advancements in strategies aim at regulating immune responses and enhancing neurovascularization have not met expecta...
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Wiley
2025-05-01
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| Series: | Advanced Science |
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| Online Access: | https://doi.org/10.1002/advs.202415459 |
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| author | Yu‐Xuan Ma Chen Lei Tao Ye Qian‐Qian Wan Kai‐Yan Wang Yi‐Na Zhu Ling Li Xu‐Fang Liu Long‐Zhang Niu Franklin R. Tay Zhao Mu Kai Jiao Li‐Na Niu |
| author_facet | Yu‐Xuan Ma Chen Lei Tao Ye Qian‐Qian Wan Kai‐Yan Wang Yi‐Na Zhu Ling Li Xu‐Fang Liu Long‐Zhang Niu Franklin R. Tay Zhao Mu Kai Jiao Li‐Na Niu |
| author_sort | Yu‐Xuan Ma |
| collection | DOAJ |
| description | Abstract Diabetes mellitus is a metabolic disorder associated with an increased risk of fractures and delayed fracture healing, leading to a higher prevalence of bone defects. Recent advancements in strategies aim at regulating immune responses and enhancing neurovascularization have not met expectations. This study demonstrates that a silicon‐based strategy significantly enhances vascularization and innervation, thereby optimizing the repair of diabetic bone defects. Silicon improves mitochondrial function and modulates mitochondrial fission dynamics in macrophages via the Drp1‐Mff signaling pathway. Subsequently, functional mitochondria are transferred from macrophages to endothelial and neuronal cells through microvesicles, providing a protective mechanism for blood vessels and peripheral nerves during early wound healing. On this basis, an optimized strategy combining a silicified collagen scaffold with a Drp1‐Fis1 interaction inhibitor is used to further regulate mitochondrial fission in macrophages and enhance the trafficking of functional mitochondria into stressed receptor cells. In diabetic mice with critical‐sized calvarial defects, the silicon‐based treatment significantly promotes vessel formation, nerve growth, and mineralized tissue development. These findings provide therapeutic insights into the role of silicon in promoting diabetic bone regeneration and highlight the importance of intercellular communication in diabetic conditions. |
| format | Article |
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| institution | OA Journals |
| issn | 2198-3844 |
| language | English |
| publishDate | 2025-05-01 |
| publisher | Wiley |
| record_format | Article |
| series | Advanced Science |
| spelling | doaj-art-6fd01d63d9004beab8b72afad5a729a62025-08-20T01:52:42ZengWileyAdvanced Science2198-38442025-05-011219n/an/a10.1002/advs.202415459Silicon Enhances Functional Mitochondrial Transfer to Improve Neurovascularization in Diabetic Bone RegenerationYu‐Xuan Ma0Chen Lei1Tao Ye2Qian‐Qian Wan3Kai‐Yan Wang4Yi‐Na Zhu5Ling Li6Xu‐Fang Liu7Long‐Zhang Niu8Franklin R. Tay9Zhao Mu10Kai Jiao11Li‐Na Niu12State Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration National Clinical Research Center for Oral Diseases Shaanxi Key Laboratory of Stomatology Department of Prosthodontics School of Stomatology The Fourth Military Medical University Xi'an 710032 ChinaState Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration National Clinical Research Center for Oral Diseases Shaanxi Key Laboratory of Stomatology Department of Prosthodontics School of Stomatology The Fourth Military Medical University Xi'an 710032 ChinaState Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration National Clinical Research Center for Oral Diseases Shaanxi Key Laboratory of Stomatology Department of Prosthodontics School of Stomatology The Fourth Military Medical University Xi'an 710032 ChinaState Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration National Clinical Research Center for Oral Diseases Shaanxi Key Laboratory of Stomatology Department of Prosthodontics School of Stomatology The Fourth Military Medical University Xi'an 710032 ChinaState Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration National Clinical Research Center for Oral Diseases Shaanxi Key Laboratory of Stomatology Department of Prosthodontics School of Stomatology The Fourth Military Medical University Xi'an 710032 ChinaState Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration National Clinical Research Center for Oral Diseases Shaanxi Key Laboratory of Stomatology Department of Prosthodontics School of Stomatology The Fourth Military Medical University Xi'an 710032 ChinaState Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration National Clinical Research Center for Oral Diseases Shaanxi Key Laboratory of Stomatology Department of Prosthodontics School of Stomatology The Fourth Military Medical University Xi'an 710032 ChinaState Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration National Clinical Research Center for Oral Diseases Shaanxi Key Laboratory of Stomatology Department of Prosthodontics School of Stomatology The Fourth Military Medical University Xi'an 710032 ChinaState Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration National Clinical Research Center for Oral Diseases Shaanxi Key Laboratory of Stomatology Department of Prosthodontics School of Stomatology The Fourth Military Medical University Xi'an 710032 ChinaThe Dental College of Georgia Augusta University Augusta GA 30912 USAState Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration School of Stomatology The Fourth Military Medical University Xi'an 710032 ChinaDepartment of Stomatology Tangdu hospital State Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration & National Clinical Research Center for Oral Diseases & Shaanxi Key Laboratory of Stomatology School of Stomatology & Shaanxi Key Laboratory of Stomatology School of Stomatology The Fourth Military Medical University Xi'an Shaanxi 710032 ChinaState Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration National Clinical Research Center for Oral Diseases Shaanxi Key Laboratory of Stomatology Department of Prosthodontics School of Stomatology The Fourth Military Medical University Xi'an 710032 ChinaAbstract Diabetes mellitus is a metabolic disorder associated with an increased risk of fractures and delayed fracture healing, leading to a higher prevalence of bone defects. Recent advancements in strategies aim at regulating immune responses and enhancing neurovascularization have not met expectations. This study demonstrates that a silicon‐based strategy significantly enhances vascularization and innervation, thereby optimizing the repair of diabetic bone defects. Silicon improves mitochondrial function and modulates mitochondrial fission dynamics in macrophages via the Drp1‐Mff signaling pathway. Subsequently, functional mitochondria are transferred from macrophages to endothelial and neuronal cells through microvesicles, providing a protective mechanism for blood vessels and peripheral nerves during early wound healing. On this basis, an optimized strategy combining a silicified collagen scaffold with a Drp1‐Fis1 interaction inhibitor is used to further regulate mitochondrial fission in macrophages and enhance the trafficking of functional mitochondria into stressed receptor cells. In diabetic mice with critical‐sized calvarial defects, the silicon‐based treatment significantly promotes vessel formation, nerve growth, and mineralized tissue development. These findings provide therapeutic insights into the role of silicon in promoting diabetic bone regeneration and highlight the importance of intercellular communication in diabetic conditions.https://doi.org/10.1002/advs.202415459bioactive silicondiabetic bone defectsmacrophagesmitochondrial transferneuralvascular |
| spellingShingle | Yu‐Xuan Ma Chen Lei Tao Ye Qian‐Qian Wan Kai‐Yan Wang Yi‐Na Zhu Ling Li Xu‐Fang Liu Long‐Zhang Niu Franklin R. Tay Zhao Mu Kai Jiao Li‐Na Niu Silicon Enhances Functional Mitochondrial Transfer to Improve Neurovascularization in Diabetic Bone Regeneration Advanced Science bioactive silicon diabetic bone defects macrophages mitochondrial transfer neural vascular |
| title | Silicon Enhances Functional Mitochondrial Transfer to Improve Neurovascularization in Diabetic Bone Regeneration |
| title_full | Silicon Enhances Functional Mitochondrial Transfer to Improve Neurovascularization in Diabetic Bone Regeneration |
| title_fullStr | Silicon Enhances Functional Mitochondrial Transfer to Improve Neurovascularization in Diabetic Bone Regeneration |
| title_full_unstemmed | Silicon Enhances Functional Mitochondrial Transfer to Improve Neurovascularization in Diabetic Bone Regeneration |
| title_short | Silicon Enhances Functional Mitochondrial Transfer to Improve Neurovascularization in Diabetic Bone Regeneration |
| title_sort | silicon enhances functional mitochondrial transfer to improve neurovascularization in diabetic bone regeneration |
| topic | bioactive silicon diabetic bone defects macrophages mitochondrial transfer neural vascular |
| url | https://doi.org/10.1002/advs.202415459 |
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