Injectable Magnesium-Bisphosphonate MOF-Based Bone Adhesive Prevents Excessive Fibrosis for Osteoporotic Fracture Repair

Current clinical approaches to promote osteoporotic fracture healing primarily target osteoclast biology, overlooking the negative regulatory role of fibroblasts in fracture healing. Perioperative bisphosphonates (BPs) used in anti-osteoporosis treatment for osteoporotic fractures have become a consensus worldwide. However, excessive fibrosis is induced simultaneously, leading to fracture non-union and atypical femur fractures. It is highly desirable to inhibit osteoclasts but block fibrosis. In this study, an magnesium ions (Mg2+)-BPs MOF-based bone adhesive material was designed to down-regulate SOST and weaken SOST/TGF-ß signaling pathway through Mg2+ through transcriptome analysis, thus inhibiting fibrotic differentiation and subsequent disordered mineralization. Overall design: In this study, a Mg-ALN MOF-based bone adhesive material was designed to antagonize the pathological characteristics of bone fibrosis induced by bisphosphonate (ALN) through Mg2+. Gel, ALN+Gel and Mg-ALN@Gel samples were analyzed by transcriptome sequencing. Mg2+ inhibited fibrotic differentiation by down-regulating SOST and attenuating SOST/TGF-ß signaling pathway.