Gelatin-Based Electrospun Nanofibrous Membranes for Treatment of Intrauterine Adhesion

As the leading cause of uterine factor infertility, intrauterine adhesion (IUA) poses a severe threat to the fertility and mental health of women at childbearing age. However, the efficacy of the present clinical treatments is unsatisfactory. There remains an urgent need to develop a safe, effective, and clinically feasible therapeutic strategy to restore the damaged endometrium. Here, we fabricated a gelatin-based electrospun nanofibrous membrane (GENM) via electrospinning and chemical crosslinking technique and characterized its properties. The anti-fibrotic and pro-angiogenic effects of GENM were evaluated in cellular models. A rat IUA model induced by mechanical scraping was established to assess the therapeutic efficacy of GENM by histological staining. Additionally, bulk RNA sequencing was performed to explore the underlying mechanisms. Our results demonstrated GENM inhibited transforming growth factor beta 1 (TGF-β1) induced fibrosis in human endometrial stromal cells (HESCs) and promoted angiogenesis of human umbilical vein endothelial cells (HUVECs). Animal experiments also suggested that GENM significantly improved endometrial receptivity and neovascularization while reducing fibrosis in the rat IUA model. RNA sequencing further identified several signaling pathways contributing to uncovering its mechanism of action. These findings indicate that GENM holds significant potential for clinical application in the management of IUA.