Synthesis of Cyclodextrin-Based Multifunctional Biocompatible Hydrogels and Their Use in the Prevention of Intrauterine Adhesions (Asherman's Syndrome) after Surgical Injury

Asherman's syndrome, which can occur during the regeneration of damaged uterine tissue after surgical interventions, is a significant health problem in women. This study aimed to acquire and characterize cyclodextrin-based hydrogels, which can be used to prevent Asherman's syndrome, and investigate their effectiveness with biomedical applications. A series of hydrogels were synthesized from the cross-linking of beta-cyclodextrin and different polyphenols with epoxy-functional PEG. Their chemical, physical, and biological properties were subsequently determined. The results demonstrated that the cyclodextrin-based hydrogels had a porous structure, high swelling ratio, good injectability, drug release ability, and antioxidant activity. Cell culture results illustrated that the hydrogels had no significant cytotoxicity toward L929 fibroblast cells. Considering all properties, the beta-CD-PEG-600-Ec hydrogel showed the most satisfactory properties rather than other ones. The potential of this hydrogel in preventing Asherman's syndrome was evaluated in a rat model. The results revealed that the beta-estradiol- and melatonin-loaded cyclodextrin-based multifunctional hydrogel group both structurally and mechanically showed an antiadhesion effect in the uterus and a therapeutic effect on the damage with the beta-estradiol and melatonin that it contains compared to the Asherman (ASH) group. This double drug-loaded hydrogel can be a promising candidate for preventing Asherman's syndrome due to its versatile properties.