Intrauterine adhesions (IUA) are a common gynecologic disease worldwide that can lead to menstrual irregularities, infertility, or repeated pregnancy loss. Biomaterials are used as a physical barrier to separate damaged uterine walls and prevent tissue adhesion. However, most biomaterials cannot prevent or even increase inflammation and fibrosis during implantation, which is crucial for IUA development, limiting their application in treatment. To address this, we developed a hydrophilic hydrogel film with a negative surface potential that can absorb excess positive proinflammatory cytokines to alleviate the inflammatory response and limit endometrial fibre formation. In vitro, the hydrogel film exhibits good biocompatibility and anti-fibroblast adhesion properties, and in vivo, they downregulate the expression level of proinflammatory cytokines and reduce the degree of fibrosis. After loading the hydrogel film with vascular endothelial growth factor (VEGF) and implanting it into the injured rat endometrial cavity, the increased local microvessels and higher endometrial thickness indicated improved endometrial regeneration during IUA treatment. In summary, the hydrogel film capable of efficiently reducing inflammation and decreasing fibrosis provides a promising strategy for treating and preventing IUA difficulties, with broad clinical application potential.
Sisi Zhang,Erna Jia,Weiqi Zhang,Zhiying Wang,Da Deng,Yixin Zhang,Xuefeng Huang,Qingquan Tian,Ying Tan,Bujun Wang,Feng Lin
The development of novel therapeutic approaches to facilitate endometrial repair and regeneration while preventing adhesion recurrence is a crucial research objective aimed at enhancing clinical outcomes for women with intrauterine adhesions (IUA). In this study, we introduced an injectable Alg-GMA/PTSB zwitterionic hydrogel, characterized by excellent biocompatibility, anti-protein adsorption properties, and biodegradability. In a rat model, the hydrogel significantly promoted the regeneration and angiogenesis of damaged endometrial tissue, leading to improved recovery of epithelial cells, glands, proliferation, and vascularization. Furthermore, it exhibited the ability to suppress cellular apoptosis and collagen deposition, thereby mitigating fibrosis. Additionally, the hydrogel restored the expression of estrogen/progesterone receptors and endometrial receptivity markers, contributing to enhanced embryo implantation and fertility. These findings underscore the potential of the hydrogel as a promising therapeutic strategy for addressing endometrial injury, reducing fibrosis, restoring fertility, and ultimately improving outcomes for women with IUA.