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Injectable magnesium-bisphosphonate MOF-based bone adhesive prevents excessive fibrosis for osteoporotic fracture repair
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Injectable magnesium-bisphosphonate MOF-based bone adhesive prevents excessive fibrosis for osteoporotic fracture repair
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Journal Article
Injectable magnesium-bisphosphonate MOF-based bone adhesive prevents excessive fibrosis for osteoporotic fracture repair
2025
Overview
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 Mg
2+
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.
Excessive fibrosis triggered by bisphosphonates impairs fracture healing in osteoporotic bone. Here, the authors develop an injectable magnesium-alendronate MOF-based hydrogel adhesive and show it prevents fibrosis and enhances bone repair, improving healing strength in an osteoporotic rat model.
Publisher
Nature Publishing Group UK,Nature Publishing Group,Nature Portfolio
Subject
/ 13/51
/ 14/19
/ 140/146
/ 147/143
/ 147/3
/ 38/77
/ 38/91
/ Adaptor Proteins, Signal Transducing - metabolism
/ Animals
/ Bone Resorption - drug therapy
/ Bones
/ Callus
/ Diphosphonates - administration & dosage
/ Diphosphonates - pharmacology
/ Female
/ Fibrosis
/ Fibrosis - prevention & control
/ Fracture Healing - drug effects
/ Gelatin
/ Healing
/ Humanities and Social Sciences
/ Humans
/ Ions
/ Magnesium - administration & dosage
/ Metal-Organic Frameworks - administration & dosage
/ Metal-Organic Frameworks - chemistry
/ Metal-Organic Frameworks - pharmacology
/ Mice
/ Osteoporotic Fractures - drug therapy
/ Osteoporotic Fractures - pathology
/ Science
/ Signal Transduction - drug effects
