Injectable, antifouling granular zwitterionic hydrogels for preventing postoperative intrauterine adhesion and restoring fertility.

The development of innovative therapeutic strategies to support endometrial repair and regeneration while preventing adhesion recurrence represents a critical research priority for improving clinical outcomes in women with intrauterine adhesions (IUA). Herein, a granular zwitterionic poly(sulfobetaine methacrylate) (G-PSBMA) hydrogel was engineered to exhibit injectability, biocompatibility and robust antifouling properties as quantified by reduced nonspecific protein adsorption. Therapeutic efficacy was demonstrated in a rat model, where the hydrogel distinctly reduced collagen deposition, attenuated fibrotic progression, and promoted morphological restoration of the endometrium. Furthermore, significant reductions in inflammatory responses in vivo were achieved through diminished macrophage infiltration and downregulation of pro-inflammatory cytokines, including IL-1β and TNF-α. The hydrogel was also shown to enhance endometrial proliferation, stimulate angiogenesis, and improve endometrial receptivity as indicated by upregulated expression of receptivity markers. Functional recovery was evidenced by successful embryo implantation post-treatment, underscoring the hydrogel's potential to restore fertility. These findings collectively suggest that the granular PSBMA hydrogel represents a therapeutic platform for addressing endometrial injury, modulating inflammation, and facilitating fertility restoration, thereby offering potential for improved clinical outcomes in IUA management. STATEMENT OF SIGNIFICANCE: Current intrauterine adhesions (IUA) treatments, such as hormonal therapy and surgical adhesiolysis, suffer from high recurrence rates and limited efficacy. This work innovates with an injectable granular zwitterionic PSBMA hydrogel-adaptive to uterine contours, antifouling (reduced nonspecific adhesion), and biocompatible. It attenuates fibrosis (less collagen), suppresses inflammation (diminished macrophages/IL-1β/TNF-α), promotes endometrial proliferation/angiogenesis, and restores receptivity/fertility (successful implantation in rats). This multifunctional platform advances IUA treatment and enables clinical translation potential in reproductive medicine.