Sprayable metal-phenolic network tailored antioxidant powder remodels endometrial oxidative-inflammatory homeostasis for chronic endometritis therapy and fertility restoration.

Abstract

Chronic endometritis (CE) is a persistent inflammatory disorder of the endometrium characterized by aberrant plasma cell infiltration and strongly associated with female infertility. CE pathogenesis is driven by persistent microbial stimulation, excessive reactive oxygen species (ROS) accumulation, and local immune dysregulation, whereas antibiotics and hysteroscopic surgery do not sufficiently resolve the sustained oxidative-inflammatory microenvironment. A sprayable antioxidant powder, RuO₂@GelMA@TA-Fe³⁺ (RGTF), is developed for localized remodeling of endometrial oxidative-inflammatory homeostasis. A tannic acid-Fe³⁺ metal-phenolic network (MPN) serves as a functional interfacial layer, providing wet-tissue adhesion, prolonged local retention, and complementary free-radical scavenging, while embedded RuO₂ nanozymes enable efficient ROS elimination. Optimized RGTF exhibits favorable sprayability, hydration-triggered tissue adhesion, and robust scavenging activity against hydrogen peroxide (H₂O₂) and multiple representative free radicals. In vitro, RGTF reduces intracellular ROS in H₂O₂-stimulated human endometrial stromal cells (HESCs) and promotes macrophage transition from a pro-inflammatory to a reparative phenotype. In a lipopolysaccharide (LPS)-induced rat CE model, local RGTF treatment alleviates oxidative damage and inflammation, promotes endometrial structural restoration, and rescues fertility-related dysfunction. This MPN-enabled platform provides a promising local strategy for CE intervention.