Degradable Endometrial Repair Membrane (DERM) promoted the endometrial regeneration in intrauterine adhesions therapy

Following injury from medical procedures or infections, the endometrium may fail to regenerate, leading to the formation of scar tissue that results in intrauterine adhesion, potentially disrupting normal endometrial function and contributing to infertility. Regenerative medicine is regarded as a promising solution to this concern, potentially providing effective treatment methods for the regeneration of injured human endometrium. Herein, we fabricated a degradable endometrial repair membrane (DERM) mainly composed of extracellular matrix, which acts as an intrauterine physical barrier and supports endometrial regeneration. In this study, we explored the role of DERM in epithelial transformation, anti-fibrosis, and angiogenesis using both an in vitro cell model and an in vivo electrothermal-induced rabbit IUA model. In vitro, the DERM effectively reduced the expression of fibrosis markers (FN1, COL1A1 and α-SMA) while promoting the expression of epithelial-related markers (CDH1 and CK19) in primary human endometrial stromal cells (HESCs) and angiogenesis-related factors (VEGFA and VEGFR2) in HUVECSs. The rabbit electrothermal injury model was used to mimic clinical electrosurgical adhesiolysis. In vivo, HE staining revealed DERM significantly accelerated endometrial regeneration, angiogenesis, and restored uterine functionality; Masson staining confirmed the deposition of collagen in endometrium of rabbits was notably reduced following the DERM treatment. Moreover, DERM remarkbly upregulated CDH1 and CK19 expression, and gradually degraded in the uterine cavity to avoid inflammatory irritation. In conclusion, the DERM facilitated the repair and regeneration of the endometrium, suggesting a promising new therapeutic approach for endometrial repair.