A multifunctional self-assembled hydrogel with bactericidal activity and macrophage metabolic reprogramming for diabetic bone defect repair
Diabetic bone defects are associated with chronic inflammation, impaired healing, and high susceptibility to infection, posing serious clinical challenges. Recent studies have identified macrophage metabolic dysfunction as a key contributor to this impaired regenerative process. Targeting macrophage...
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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/S259000642500732X |
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| author | Liangliang Wang Zebin Wu Xu Chen Jiaxiang Bai Wenming Li Gaoran Ge Wei Zhang Wenhao Li Yi Qin Gongyin Zhao Yuji Wang Guoqing Pan Yaozeng Xu Dechun Geng |
| author_facet | Liangliang Wang Zebin Wu Xu Chen Jiaxiang Bai Wenming Li Gaoran Ge Wei Zhang Wenhao Li Yi Qin Gongyin Zhao Yuji Wang Guoqing Pan Yaozeng Xu Dechun Geng |
| author_sort | Liangliang Wang |
| collection | DOAJ |
| description | Diabetic bone defects are associated with chronic inflammation, impaired healing, and high susceptibility to infection, posing serious clinical challenges. Recent studies have identified macrophage metabolic dysfunction as a key contributor to this impaired regenerative process. Targeting macrophage metabolism offers a promising strategy to rebalance the inflammatory microenvironment and promote bone repair. Metformin, a well-established antidiabetic agent, has been shown to reprogram macrophage metabolism by enhancing oxidative phosphorylation and promoting anti-inflammatory M2 polarization. However, its therapeutic efficacy is limited by poor local retention and lack of antibacterial activity. To overcome these limitations, we developed a multifunctional self-assembled hydrogel (M − C Gel@Met) based on multivalent PEG-antimicrobial polymers and clay nanosheets, enabling sustained co-delivery of metformin and antimicrobial peptides. This hydrogel not only mimics the dynamic structure of the extracellular matrix and adapts to irregular defects, but also provides potent antibacterial protection while reprogramming macrophage metabolism. In diabetic bone defect models, M − C Gel@Met effectively alleviated inflammation, enhanced osteogenesis, and accelerated bone regeneration. Overall, this strategy presents a biomaterial-based immunometabolic strategy integrating infection control and metabolic modulation for diabetic bone repair. |
| format | Article |
| id | doaj-art-7b6bd7518f1f45d8a85cf16d8ead51de |
| institution | DOAJ |
| issn | 2590-0064 |
| language | English |
| publishDate | 2025-10-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Materials Today Bio |
| spelling | doaj-art-7b6bd7518f1f45d8a85cf16d8ead51de2025-08-20T02:56:39ZengElsevierMaterials Today Bio2590-00642025-10-013410216210.1016/j.mtbio.2025.102162A multifunctional self-assembled hydrogel with bactericidal activity and macrophage metabolic reprogramming for diabetic bone defect repairLiangliang Wang0Zebin Wu1Xu Chen2Jiaxiang Bai3Wenming Li4Gaoran Ge5Wei Zhang6Wenhao Li7Yi Qin8Gongyin Zhao9Yuji Wang10Guoqing Pan11Yaozeng Xu12Dechun Geng13Department of Orthopaedics, The First Affiliated Hospital of Soochow University, Suzhou, 215006, China; Department of Orthopaedics, The Second People's Hospital of Changzhou, The Third Affiliated Hospital of Nanjing Medical University, Changzhou Medical Center, Nanjing Medical University, Changzhou, 213003, ChinaDepartment of Orthopaedics, The First Affiliated Hospital of Soochow University, Suzhou, 215006, ChinaInstitute for Advanced Materials, School of Materials Science and Engineering, Jiangsu University, Zhenjiang, 212013, ChinaDepartment of Orthopedics, Centre for Leading Medicine and Advanced Technologies of IHM, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, 230001, ChinaDepartment of Orthopaedics, The First Affiliated Hospital of Soochow University, Suzhou, 215006, ChinaDepartment of Orthopaedics, The First Affiliated Hospital of Soochow University, Suzhou, 215006, ChinaDepartment of Orthopaedics, The First Affiliated Hospital of Soochow University, Suzhou, 215006, ChinaDepartment of Orthopaedics, The First Affiliated Hospital of Soochow University, Suzhou, 215006, ChinaDepartment of Orthopaedics, The First Affiliated Hospital of Soochow University, Suzhou, 215006, ChinaDepartment of Orthopaedics, The Second People's Hospital of Changzhou, The Third Affiliated Hospital of Nanjing Medical University, Changzhou Medical Center, Nanjing Medical University, Changzhou, 213003, ChinaDepartment of Orthopaedics, The Second People's Hospital of Changzhou, The Third Affiliated Hospital of Nanjing Medical University, Changzhou Medical Center, Nanjing Medical University, Changzhou, 213003, China; Corresponding author.Institute for Advanced Materials, School of Materials Science and Engineering, Jiangsu University, Zhenjiang, 212013, China; Corresponding author.Department of Orthopaedics, The First Affiliated Hospital of Soochow University, Suzhou, 215006, China; Corresponding author.Department of Orthopaedics, The First Affiliated Hospital of Soochow University, Suzhou, 215006, China; Corresponding author.Diabetic bone defects are associated with chronic inflammation, impaired healing, and high susceptibility to infection, posing serious clinical challenges. Recent studies have identified macrophage metabolic dysfunction as a key contributor to this impaired regenerative process. Targeting macrophage metabolism offers a promising strategy to rebalance the inflammatory microenvironment and promote bone repair. Metformin, a well-established antidiabetic agent, has been shown to reprogram macrophage metabolism by enhancing oxidative phosphorylation and promoting anti-inflammatory M2 polarization. However, its therapeutic efficacy is limited by poor local retention and lack of antibacterial activity. To overcome these limitations, we developed a multifunctional self-assembled hydrogel (M − C Gel@Met) based on multivalent PEG-antimicrobial polymers and clay nanosheets, enabling sustained co-delivery of metformin and antimicrobial peptides. This hydrogel not only mimics the dynamic structure of the extracellular matrix and adapts to irregular defects, but also provides potent antibacterial protection while reprogramming macrophage metabolism. In diabetic bone defect models, M − C Gel@Met effectively alleviated inflammation, enhanced osteogenesis, and accelerated bone regeneration. Overall, this strategy presents a biomaterial-based immunometabolic strategy integrating infection control and metabolic modulation for diabetic bone repair.http://www.sciencedirect.com/science/article/pii/S259000642500732XMacrophageMetabolic reprogrammingBone defectHydrogelMetformin |
| spellingShingle | Liangliang Wang Zebin Wu Xu Chen Jiaxiang Bai Wenming Li Gaoran Ge Wei Zhang Wenhao Li Yi Qin Gongyin Zhao Yuji Wang Guoqing Pan Yaozeng Xu Dechun Geng A multifunctional self-assembled hydrogel with bactericidal activity and macrophage metabolic reprogramming for diabetic bone defect repair Materials Today Bio Macrophage Metabolic reprogramming Bone defect Hydrogel Metformin |
| title | A multifunctional self-assembled hydrogel with bactericidal activity and macrophage metabolic reprogramming for diabetic bone defect repair |
| title_full | A multifunctional self-assembled hydrogel with bactericidal activity and macrophage metabolic reprogramming for diabetic bone defect repair |
| title_fullStr | A multifunctional self-assembled hydrogel with bactericidal activity and macrophage metabolic reprogramming for diabetic bone defect repair |
| title_full_unstemmed | A multifunctional self-assembled hydrogel with bactericidal activity and macrophage metabolic reprogramming for diabetic bone defect repair |
| title_short | A multifunctional self-assembled hydrogel with bactericidal activity and macrophage metabolic reprogramming for diabetic bone defect repair |
| title_sort | multifunctional self assembled hydrogel with bactericidal activity and macrophage metabolic reprogramming for diabetic bone defect repair |
| topic | Macrophage Metabolic reprogramming Bone defect Hydrogel Metformin |
| url | http://www.sciencedirect.com/science/article/pii/S259000642500732X |
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