An Injectable ROS-Responsive Nanozyme Hydrogel Regulates the Uterine Microenvironment to Reverse Intrauterine Adhesions

Current treatments, such as hysteroscopic adhesiolysis combined with hormonal therapy or physical barriers, still show high recurrence rates and are unable to simultaneously regulate the interconnected pathological processes of inflammation, oxidative stress, and fibrosis.

In this study, we developed an injectable ROS-responsive hydrogel (CeTA@GPP) loaded with cerium–tannic acid nanoenzymes (CeTA). Unlike passive physical barriers, this hydrogel system remains stable under physiological conditions but can be selectively cleaved in ROS-enriched inflammatory microenvironments, thereby enabling on-demand, lesion-localized CeTA delivery. This system exhibits superoxide dismutase (SOD)- and catalase (CAT)-mimetic activities, allowing it to scavenge excessive ROS, alleviate oxidative stress, restore mitochondrial membrane potential, promote macrophage polarization from the pro-inflammatory M1 phenotype toward the anti-inflammatory M2 phenotype, and reverse TGF-β1-induced fibrosis in endometrial stromal cells.