2. Academic Validation
  3. Injectable magnesium-bisphosphonate MOF-based bone adhesive prevents excessive fibrosis for osteoporotic fracture repair

Injectable magnesium-bisphosphonate MOF-based bone adhesive prevents excessive fibrosis for osteoporotic fracture repair

  • Nat Commun. 2025 Jul 1;16(1):5679. doi: 10.1038/s41467-025-60853-8.
Tianhua Xiao # 1 2 3,  Zunlei Gong # 2 3,  Dongming Duan 2 3,  Hui Yu 2 3,  Song Liu 2 3,  Yuhe Jiang 4,  Xudan Xing 2 3,  Zenghui Wu 2 3,  Le Wang 2 3,  Xuebin B Yang 5,  Giuseppe Tronci 5,  Chengyun Ning 6,  Guoxin Tan 7,  Lei Zhou 8 9
Affiliations

Affiliations

  • 1 School of Chemical Engineering and Light Industry, Guangdong University of Technology, Guangzhou, China.
  • 2 Department of Orthopaedic Surgery, Guangzhou Key Laboratory of Spine Disease Prevention and Treatment, The Third Affiliated Hospital, Guangzhou Medical University, Guangzhou, China.
  • 3 Guangdong Provincial Key Laboratory of Major Obstetric Diseases, Guangdong Provincial Clinical Research Center for Obstetrics and Gynecology, The Third Affiliated Hospital, Guangzhou Medical University, Guangzhou, China.
  • 4 College of Osteopathic Medicine, New York Institute of Technology, New York, NY, USA.
  • 5 School of Dentistry, St. James's University Hospital, University of Leeds, Leeds, UK.
  • 6 School of Materials Science and Engineering, National Engineering Research Center for Tissue Restoration and Reconstruction, South China University of Technology, Guangzhou, China.
  • 7 School of Chemical Engineering and Light Industry, Guangdong University of Technology, Guangzhou, China. tanguoxin@126.com.
  • 8 Department of Orthopaedic Surgery, Guangzhou Key Laboratory of Spine Disease Prevention and Treatment, The Third Affiliated Hospital, Guangzhou Medical University, Guangzhou, China. zhoul@gzhmu.edu.cn.
  • 9 Guangdong Provincial Key Laboratory of Major Obstetric Diseases, Guangdong Provincial Clinical Research Center for Obstetrics and Gynecology, The Third Affiliated Hospital, Guangzhou Medical University, Guangzhou, China. zhoul@gzhmu.edu.cn.
  • # Contributed equally.
PMID: 40593608 DOI: 10.1038/s41467-025-60853-8
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.

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