Magnesium ion hydrogel enhances resistance to radiation-induced bone injury by modulating the bone immune microenvironment and promoting microvascularization

作者：Qiong Wang, Xinpeng Hu, Zeyu Xiao, Kunlin Ye, Jia Li, Jiaxin Tan, Nuonuo Rao, Dong Zhang, Guodong Sun, Mingxiang Cai, Ni Shao, Nianlan Cheng, Le Bai, Xiangning Liu, Changzheng Shi, Liangping Luo · 发表于：Regenerative Biomaterials · 年份：2025 · DOI：10.1093/rb/rbaf118 · 被引用次数：3 · 研究领域：Effects of Radiation Exposure、Bone Tissue Engineering Materials、Bone Metabolism and Diseases

Abstract Mandibular radiation-induced bone injury (RIBI) is a common, severe complication of radiotherapy with no effective treatment. The early course is clinically subtle yet pathologically complex: ionizing radiation (IR) rapidly induces microvascular dysfunction, amplifies immune-mediated inflammation and disrupts bone homeostasis. This complexity, together with safety considerations, hampers therapeutic translation. Magnesium (Mg2+) is an essential bone component whose pro-osteogenic activity is well established; nevertheless, irradiation may remodel the multi-target effects of bioactive ions, and the integrated mechanisms of Mg2+ in bone radiation injury remain to be clarified. Here, we compared local delivery of an Mg2+- crosslinked alginate hydrogel (Mg@Alg) under irradiated versus non-irradiated conditions in rats and combined macrophage and endothelial cell models to evaluate radioprotective effects and mechanisms. In our study, Mg@Alg attenuated bone loss and apoptosis within 14 days after IR, promoted M2-like macrophage polarization, and improved microvascular density and maturation, thereby contributing to inflammatory microenvironment remodeling. Mechanistically, Mg2+ intervention was accompanied by decreased ferritin, downregulation of prolyl hydroxylase domain-2 (PHD2), and stabilization of hypoxia-inducible factor-1α (HIF-1α), together with vascular endothelial growth factor A upregulation; these changes were partly reversed by Fe2+, suggesting an iron-depend...