Engineering Hydrogels for Intrauterine Adhesion Therapy and Endometrial Regeneration

Abstract

Intrauterine adhesion (IUA) is a fibrotic disorder resulting from aberrant repair following injury to the endometrial basal layer, leading to menstrual abnormalities, infertility, recurrent miscarriage, and pregnancy complications. Although hysteroscopic adhesiolysis remains the primary clinical treatment, the rate of postoperative re–adhesion is still high, especially in patients with moderate–to–severe IUA. Moreover, mechanical separation alone is often insufficient to restore intact endometrial architecture and reproductive function. Hydrogels, with their hydrated three–dimensional networks, extracellular matrix (ECM)–mimicking properties, injectability, biodegradability, tissue adhesion, and tunable delivery capacity, have evolved from passive barrier materials into multifunctional therapeutic platforms capable of regulating the pathological microenvironment and promoting tissue regeneration. Recent advances in responsive, self–healing, adhesive, antioxidant, and bioactive cargo–loaded hydrogels have expanded their applications from preventing adhesion formation toward functional endometrial reconstruction. In this review, we summarize recent progress in hydrogel–based IUA therapy, focusing on material composition, structural design, functional modification, therapeutic mechanisms, and translational considerations. Particular emphasis is placed on disease–informed hydrogel engineering strategies that integrate the unique anatomical characteristics of the uterine cavity, injury–associated microenvironment, and dynamic stages of endometrial repair. This perspective provides insights into the development of next–generation hydrogel systems for preventing re–adhesion and restoring reproductive function.