Injectable Gypsogenin‐Based Composite Hydrogel Enhances Osteoporotic Bone Regeneration by Alleviating Oxidative Injury via Promoting AMPKα Phosphorylation

作者：Yang Zheng, Rongtai Sun, Meichun Han, Congcong Yu, Tianyuan Gu, Zhenwei Wang, Pengyu Chen, Wenxiang Zeng, Helou Zhang, Yiyang Xu, Weibin Du, Ruikang Tang, Xing Zhao, Shasha Yao, Renfu Quan · 发表于：Advanced Functional Materials · 年份：2025 · DOI：10.1002/adfm.202424326 · 被引用次数：7 · 研究领域：Bone Metabolism and Diseases、Bone health and treatments、Bone Tissue Engineering Materials

Abstract Osteoporosis is characterized by an imbalance between osteoblasts and osteoclasts coupling and excessive oxidative stress in the bone microenvironment that impairs bone defect healing and increases the risk of non‐union. In this study, an injectable gypsogenin (GN)‐based organic–inorganic composite hydrogel (CCT/nHA@GN) is developed to treat osteoporotic bone defects. The hydrogel is made by grafting sodium citrate (SC) and nano‐hydroxyapatite (nHA)/GN nanoparticles onto carboxymethylated chitosan (CMCS). GN is a natural small‐molecule saponin, which shows biocompatibility and anti‐oxidant properties. The resulting hydrogel shows a well‐defined porous structure, favorable degradability, controlled drug‐release properties, and suitable rheological characteristics. Importantly, it reverses the differentiation fate of bone marrow‐derived mesenchymal stem cells (BMSCs) from osteoporotic patients and promotes angiogenesis in human umbilical vein endothelial cells (HUVECs). Furthermore, it activates the AMPKα‐FOXO3a‐CAT/MnSOD signaling pathway via AMPKα phosphorylation, thereby augmenting antioxidant stress capacity, promoting osteogenesis, inhibiting osteoclastogenesis, and ultimately rectifying the disrupted bone microenvironment. In vivo studies reveal that the bone volume to total volume (BV/TV) ratio of bones regenerated with the CCT/nHA@GN hydrogel is 2.85 times higher than that of the control group. In conclusion, these findings suggest that the injectable CCT/nHA@G...