Injectable plant phosphate coordination compounds-based adhesive hydrogel accelerates osteoporotic fracture healing by restoring bone homeostasis

Osteoporotic fractures are notoriously difficult to heal due to an imbalance between osteoblasts and osteoclasts. Current treatments often have limited efficacy or adverse side effects, highlighting the need for safer, more effective solutions. Here, we developed an injectable plant-derived phosphate coordination compound-based adhesive hydrogel to restore bone homeostasis by integrating magnesium ions (Mg2+)-phytic acid (PA) nanoparticles with aminated gelatin and aldehydated starch. The hydrogel can firmly adhere to irregular bone tissue at the fracture site and achieve achieve Mg-PA degradation in response to the osteoporotic acidic microenvironment, releasing PA and Mg2+, which modulated osteoclast and osteoblast activity, respectively. Impressively, PA inhibits osteoclastogenesis by stimulating monocyte secretion of CCN1, which competitively binds RANKL to disrupt RANKL-RANK signaling. Meanwhile, Mg2+ enhances osteoblast differentiation from bone marrow stem cells. In an ovariectomized rat model, the hydrogel significantly accelerates fracture healing (84.63% improvement over the control groups in flexural strength). This study highlights the potential of PA-based coordination compounds as a novel strategy for osteoporotic fracture treatment. In this study, MgPA-Gel adhesive was used to treat osteoporotic femoral fractures in SD rats. Femoral tissue of 1 cm length around the fracture end of the gel-only group and the MgPA-Gel group was selected for high-throughput mRNA detection, with 3 samples in each group.