Injectable magnesium-bisphosphonate MOF-based bone adhesive prevents excessive fibrosis for osteoporotic fracture repair
Abstract Current treatments for osteoporotic fractures primarily target bone-resorbing osteoclasts, but they often fail to address fibrosis—a buildup of fibrous tissue that disrupts bone healing. This fibrosis is frequently triggered by bisphosphonates, which, while effective in reducing bone loss,...
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Nature Portfolio
2025-07-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-025-60853-8 |
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| author | Tianhua Xiao Zunlei Gong Dongming Duan Hui Yu Song Liu Yuhe Jiang Xudan Xing Zenghui Wu Le Wang Xuebin B. Yang Giuseppe Tronci Chengyun Ning Guoxin Tan Lei Zhou |
| author_facet | Tianhua Xiao Zunlei Gong Dongming Duan Hui Yu Song Liu Yuhe Jiang Xudan Xing Zenghui Wu Le Wang Xuebin B. Yang Giuseppe Tronci Chengyun Ning Guoxin Tan Lei Zhou |
| author_sort | Tianhua Xiao |
| collection | DOAJ |
| description | Abstract Current treatments for osteoporotic fractures primarily target bone-resorbing osteoclasts, but they often fail to address fibrosis—a buildup of fibrous tissue that disrupts bone healing. This fibrosis is frequently triggered by bisphosphonates, which, while effective in reducing bone loss, also activate fibroblasts and impair callus formation. Here we show that an injectable hydrogel bone adhesive composed of magnesium-alendronate metal-organic frameworks (Mg-ALN MOF) embedded in a gelatin/dialdehyde starch network can simultaneously suppress bone resorption and reduce fibrosis. The Mg-ALN MOF adhesive binds firmly to irregular bone surfaces and degrades under acidic osteoporotic conditions, gradually releasing Mg2+ ions. These ions competitively bind to sclerostin (SOST), thereby interrupting the SOST/TGF-β signaling pathway that promotes fibroblast activation and abnormal collagen deposition. This dual-action mechanism significantly enhances fracture healing, resulting in a 27.8% improvement in flexural strength. Our findings suggest a promising therapeutic strategy that combines mechanical support with targeted regulation of both bone resorption and pathological fibrosis. |
| format | Article |
| id | doaj-art-4c1fe6f77397409da6262ac28c4e6f10 |
| institution | Kabale University |
| issn | 2041-1723 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj-art-4c1fe6f77397409da6262ac28c4e6f102025-08-20T04:01:41ZengNature PortfolioNature Communications2041-17232025-07-0116112210.1038/s41467-025-60853-8Injectable magnesium-bisphosphonate MOF-based bone adhesive prevents excessive fibrosis for osteoporotic fracture repairTianhua Xiao0Zunlei Gong1Dongming Duan2Hui Yu3Song Liu4Yuhe Jiang5Xudan Xing6Zenghui Wu7Le Wang8Xuebin B. Yang9Giuseppe Tronci10Chengyun Ning11Guoxin Tan12Lei Zhou13School of Chemical Engineering and Light Industry, Guangdong University of TechnologyDepartment of Orthopaedic Surgery, Guangzhou Key Laboratory of Spine Disease Prevention and Treatment, The Third Affiliated Hospital, Guangzhou Medical UniversityDepartment of Orthopaedic Surgery, Guangzhou Key Laboratory of Spine Disease Prevention and Treatment, The Third Affiliated Hospital, Guangzhou Medical UniversityDepartment of Orthopaedic Surgery, Guangzhou Key Laboratory of Spine Disease Prevention and Treatment, The Third Affiliated Hospital, Guangzhou Medical UniversityDepartment of Orthopaedic Surgery, Guangzhou Key Laboratory of Spine Disease Prevention and Treatment, The Third Affiliated Hospital, Guangzhou Medical UniversityCollege of Osteopathic Medicine, New York Institute of TechnologyDepartment of Orthopaedic Surgery, Guangzhou Key Laboratory of Spine Disease Prevention and Treatment, The Third Affiliated Hospital, Guangzhou Medical UniversityDepartment of Orthopaedic Surgery, Guangzhou Key Laboratory of Spine Disease Prevention and Treatment, The Third Affiliated Hospital, Guangzhou Medical UniversityDepartment of Orthopaedic Surgery, Guangzhou Key Laboratory of Spine Disease Prevention and Treatment, The Third Affiliated Hospital, Guangzhou Medical UniversitySchool of Dentistry, St. James’s University Hospital, University of LeedsSchool of Dentistry, St. James’s University Hospital, University of LeedsSchool of Materials Science and Engineering, National Engineering Research Center for Tissue Restoration and Reconstruction, South China University of TechnologySchool of Chemical Engineering and Light Industry, Guangdong University of TechnologyDepartment of Orthopaedic Surgery, Guangzhou Key Laboratory of Spine Disease Prevention and Treatment, The Third Affiliated Hospital, Guangzhou Medical UniversityAbstract Current treatments for osteoporotic fractures primarily target bone-resorbing osteoclasts, but they often fail to address fibrosis—a buildup of fibrous tissue that disrupts bone healing. This fibrosis is frequently triggered by bisphosphonates, which, while effective in reducing bone loss, also activate fibroblasts and impair callus formation. Here we show that an injectable hydrogel bone adhesive composed of magnesium-alendronate metal-organic frameworks (Mg-ALN MOF) embedded in a gelatin/dialdehyde starch network can simultaneously suppress bone resorption and reduce fibrosis. The Mg-ALN MOF adhesive binds firmly to irregular bone surfaces and degrades under acidic osteoporotic conditions, gradually releasing Mg2+ ions. These ions competitively bind to sclerostin (SOST), thereby interrupting the SOST/TGF-β signaling pathway that promotes fibroblast activation and abnormal collagen deposition. This dual-action mechanism significantly enhances fracture healing, resulting in a 27.8% improvement in flexural strength. Our findings suggest a promising therapeutic strategy that combines mechanical support with targeted regulation of both bone resorption and pathological fibrosis.https://doi.org/10.1038/s41467-025-60853-8 |
| spellingShingle | Tianhua Xiao Zunlei Gong Dongming Duan Hui Yu Song Liu Yuhe Jiang Xudan Xing Zenghui Wu Le Wang Xuebin B. Yang Giuseppe Tronci Chengyun Ning Guoxin Tan Lei Zhou Injectable magnesium-bisphosphonate MOF-based bone adhesive prevents excessive fibrosis for osteoporotic fracture repair Nature Communications |
| title | Injectable magnesium-bisphosphonate MOF-based bone adhesive prevents excessive fibrosis for osteoporotic fracture repair |
| title_full | Injectable magnesium-bisphosphonate MOF-based bone adhesive prevents excessive fibrosis for osteoporotic fracture repair |
| title_fullStr | Injectable magnesium-bisphosphonate MOF-based bone adhesive prevents excessive fibrosis for osteoporotic fracture repair |
| title_full_unstemmed | Injectable magnesium-bisphosphonate MOF-based bone adhesive prevents excessive fibrosis for osteoporotic fracture repair |
| title_short | Injectable magnesium-bisphosphonate MOF-based bone adhesive prevents excessive fibrosis for osteoporotic fracture repair |
| title_sort | injectable magnesium bisphosphonate mof based bone adhesive prevents excessive fibrosis for osteoporotic fracture repair |
| url | https://doi.org/10.1038/s41467-025-60853-8 |
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