Controlled-release hydrogel loaded with engineered extracellular vesicles for treatment of chronic endometritis.

Abstract

Chronic endometritis (CE) is an important factor contributing to infertility and adverse pregnancy outcomes. Current clinical management mainly relies on antibiotics such as ceftizoxime (CTX), whose efficacy is limited by poor oral bioavailability and short half-life. To address these limitations, this study developed an intelligent, responsive hydrogel incorporating Leonurus japonicus Houtt derived extracellular vesicles (EVs) loaded with CTX. The hydrogel forms sustained-release drug reservoir in situ within the uterine cavity, enabling controlled release in response to the local inflammatory microenvironment. EVs can effectively regulate the inflammatory microenvironment by inhibiting activation of NF-κB pathway and NLRP3 inflammasome, downregulating the pro-inflammatory factor TGF-α, and upregulating the anti-inflammatory factors IL-10 and TGF-β1, thereby significantly promoting endometrial repair and reducing fibrotic areas. Meanwhile, CTX provides targeted antibacterial activity to eliminate pathogens and control infection. Through exerting antibacterial, anti-inflammatory, and tissue repairing, the developed intelligent, responsive hydrogel system offers a promising strategy for treatment of CE.