Breaking the hemorrhage-ferroptosis-fibrosis axis: A ROS-responsive iron-trapping hydrogel remodels the local immune...

Intrauterine adhesions (IUA) remain a formidable clinical challenge owing to their high postoperative recurrence, which is closely associated with a hemorrhage-driven pathological microenvironment marked by iron overload, oxidative stress, and ferroptosis. Herein, we report a structure-function integrated, reactive oxygen species (ROS)-responsive hydrogel (BPC) fabricated through a facile one-pot strategy from borax, protocatechuic aldehyde (PA), and chitosan. Benefiting from a dual dynamic covalent network constructed via Schiff base and boronate ester linkages, the BPC hydrogel exhibits favorable injectability, self-healing behavior, and tissue adhesiveness, enabling efficient and minimally invasive intrauterine administration. More importantly, the BPC hydrogel serves not merely as a physical barrier but as a bioactive therapeutic matrix that synergistically integrates rapid hemostasis, iron chelation, radical scavenging, and immune regulation. By promptly arresting bleeding, the BPC hydrogel helps limit early iron accumulation associated with postoperative hemorrhage, while its intrinsic antioxidant activity mitigates oxidative stress and ferroptosis-associated endometrial injury. In a rat IUA model, the BPC hydrogel favorably remodeled the injured endometrial microenvironment by reducing local oxidative stress, shifting macrophage polarization toward a more reparative phenotype, attenuating fibrotic progression through downregulation of the TGF-β signaling axis, and improving embryo implantation outcomes. Collectively, this anti-ferroptosis-based hydrogel platform offers a promising cell-free strategy for preventing IUA recurrence and promoting functionally relevant endometrial regeneration with reproductive potential.