Engineering Self-healing Adhesive Hydrogels with Antioxidant Properties for Intrauterine Adhesion Prevention

Intrauterine adhesion (IUA) is the fibrosis within the uterine cavity. It is the second most common cause of female infertility, significantly affecting women's physical and mental health. Current treatment strategies fail to provide a satisfactory therapeutic outcome for IUA patients, leaving an enormous challenge for reproductive science. A self-healing adhesive hydrogel with antioxidant properties will be highly helpful in IUA prevention. In this work, we prepare a series of self-healing hydrogels (P10G15, P10G20, and P10G25) with antioxidant and adhesive properties. Those hydrogels exhibit good self-healing properties and can adapt themselves to different structures. They possess good injectability and fit the shape of the human uterus. Moreover, the hydrogels exhibit good tissue adhesiveness, which is desirable for stable retention and therapeutic efficacy. The in vitro experiments using P10G20 show that the adhesive effectively scavenges ABTS+, DPPH, and hydroxyl radicals, rescuing cells from oxidative stress. In addition, P10G20 offers good hemocompatibility and in vitro and in vivo biocompatibility. Furthermore, P10G20 lowers down the in vivo oxidative stress and prevents IUA with less fibrotic tissue and better endometrial regeneration in the animal model. It can effectively downregulate fibrosis-related transforming growth factor beta 1 (TGF-β1) and vascular endothelial growth factor (VEGF). Altogether, these adhesives may be a good alternative for the clinical treatment of intrauterine adhesion.