A mechanically robust and stable estradiol-loaded PHEMA-based hydrogel barrier for intrauterine adhesion treatment

Abstract

Estrogen combined with physical barrier therapy may be a prospective method to repair a damaged endometrium and prevent postsurgical re-adhesion in the treatment of intrauterine adhesions (IUAs), but there lacks a suitable scaffold with good biocompatibility, appropriate mechanical properties, and drug-releasing kinetics. Herein, a mechanically robust and stable barrier based on the poly(hydroxyethyl methacrylate) (PHEMA) hydrogel combined with estradiol-loaded mesoporous silica is designed. The network is formed by covalent bonds and noncovalent coordination bonds, which endow the hydrogel with superior mechanical properties to most reported PHEMA-based hydrogels. Meanwhile, the covalent bonds impart excellent stability to the hydrogel, which maintains its structure and mechanical properties in a simulated uterine fluid for 30 days. The excellent mechanical properties and stability are comparable to those of a typical barrier material intrauterine device (IUD), enabling the hydrogel to be retained in the uterus and removed intact like an IUD. <i>In vitro</i> and <i>in vivo</i> experiments show that the hydrogel possesses good biocompatibility similar to pure PHEMA hydrogels. In addition, the hydrogel releases estradiol continuously and stably, and exhibits a good therapeutic effect in promoting the proliferation of endometrial cells and inhibiting the progression of fibrosis. Therefore, the combinational advantages make the present hydrogel very promising in IUA treatment.