Abstract

Endometrial injury is a significant cause of female infertility, while conventional treatments suffer from drawbacks such as venous thrombosis, carcinogenic risk, antimicrobial resistance, recurrent intrauterine adhesions (IUAs), and suboptimal therapeutic efficacy. To address these challenges, we have developed an injectable dynamic hydrogel based on oxidized dextran and lysozyme. This formulation enables minimally invasive syringe delivery to the uterine cavity, where it undergoes rapid self-crosslinking to establish a protective and therapeutic barrier. Our hydrogel exhibits tunable mechanical properties and degradation rate. Besides, it possesses intrinsic antibacterial and anti-inflammatory activities arising from the dissociated constitutive biomacromolecules. In vitro studies demonstrated the hydrogel's capacity to combat bacterial infection and modulate macrophage polarization from pro-inflammatory M1 to reparative M2 phenotype. In vivo evaluations confirmed significant promotion of endometrial regeneration by it through dual mechanisms: inhibition of pathological collagen deposition and stimulation of functional angiogenesis. This multifunctional hydrogel platform thus represents a transformative approach for endometrial repair with clinical translation potential.