Xiao Tianhua, Gong Zunlei, Duan Dongming, Yu Hui, Liu Song, Jiang Yuhe, Xing Xudan, Wu Zenghui, Wang Le, Yang Xuebin B, Tronci Giuseppe, Ning Chengyun, Tan Guoxin, Zhou Lei
School of Chemical Engineering and Light Industry, Guangdong University of Technology, Guangzhou, China.
Department of Orthopaedic Surgery, Guangzhou Key Laboratory of Spine Disease Prevention and Treatment, The Third Affiliated Hospital, Guangzhou Medical University, Guangzhou, China.
Nat Commun. 2025 Jul 1;16(1):5679. doi: 10.1038/s41467-025-60853-8.
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 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.
目前针对骨质疏松性骨折的治疗主要针对骨吸收破骨细胞，但往往无法解决纤维化问题——纤维化是一种纤维组织堆积，会干扰骨愈合。这种纤维化通常由双膦酸盐引发，双膦酸盐虽然能有效减少骨质流失，但也会激活成纤维细胞并损害骨痂形成。在此，我们展示了一种可注射水凝胶骨粘合剂，它由嵌入明胶/二醛淀粉网络中的阿仑膦酸镁金属有机框架（Mg-ALN MOF）组成，能够同时抑制骨吸收并减少纤维化。Mg-ALN MOF粘合剂牢固地结合在不规则骨表面，并在酸性骨质疏松条件下降解，逐渐释放镁离子。这些离子与硬化蛋白（SOST）竞争性结合，从而中断促进成纤维细胞激活和异常胶原蛋白沉积的SOST/TGF-β信号通路。这种双作用机制显著增强骨折愈合，使弯曲强度提高27.8%。我们的研究结果表明了一种有前景的治疗策略，即将机械支撑与对骨吸收和病理性纤维化的靶向调节相结合。
