Ru single-atom nanozymes targeting ROS-ferroptosis pathways for enhanced endometrial regeneration in intrauterine adhesion therapy

作者：Yuxiang Liang, Jian Meng, Zhaowei Yu, Yuqian Guo, Xiao Zhang, Yujia Yan, Shaobo Du, Shanshan Jin, Jing Li, Hailan Yang, Xiaozheng Zhang, Zhizhen Liu, Liping Li, Jun Xie · 发表于：Biomaterials · 年份：2024 · DOI：10.1016/j.biomaterials.2024.122923 · 被引用次数：25 · 研究领域：Pregnancy and preeclampsia studies、Pregnancy and Medication Impact、Reproductive System and Pregnancy

Intrauterine adhesion (IUA) presents a significant challenge in gynecology, characterized by excessive fibrosis and compromised reproductive function, leading to severe infertility. Although biocompatible hydrogels integrated with stem cells offer a promising approach for IUA therapy, clinical applications remain limited. Recent studies have highlighted the role of ferroptosis and reactive oxygen species (ROS) in IUA pathogenesis, yet strategies targeting ferroptosis through antioxidant stress are underexplored. This study investigates the therapeutic effects and mechanisms of a Ru-Single-Atom Nanozyme (Ru-SAN) incorporated into chitosan hydrogel for treating IUA. Ru-SAN, which mimics the enzyme activities of catalase, superoxide dismutase, and glutathione peroxidase, effectively clears excess ROS and shows promise in treating oxidative stress-induced diseases. The results demonstrate the superior antioxidative capabilities of Ru-SAN, significantly suppressing the ROS-ferroptosis cycle at the injury site. This creates a favorable microenvironment for post-injury repair by inhibiting inflammation, enhancing mesenchymal-to-epithelial transformation, promoting angiogenesis, and polarizing M2 macrophages. Importantly, it mitigates adverse repair outcomes from inflammation and excessive collagen fiber deposition, ultimately restoring uterine glandular structures and thickness, thereby achieving the ultimate goal of restoring fertility and live birth rates. In conclusion, our study...