Using 17β‐estradiol heparin‐poloxamer thermosensitive hydrogel to enhance the endometrial regeneration and functional recovery of intrauterine adhesions in a rat model

Mechanical damage or infection to the endometrium can lead to the formation of adhesions in the uterine cavity, which may result in reduced reproductive outcome and/or pregnancy complications. The prognosis of this disease is poor due to few effective treatments and the complex environment of endometrium. Heparin-Poloxamer Hydrogel (HP hydrogel) is a nontoxic and biodegradable biomaterial, which has been commonly used as a sustained-release delivery system. In this study, we applied a mini-endometrial curette to scrape the endometrium of rats to mimic the process of curettage in patients. After the establishment of IUA model in rats, we injected the thermo-sensitive hydrogel(E₂-HP hydrogel) into the injured uterine cavity and evaluated the therapeutic effect of E₂-HP hydrogel on the recovery of IUA. Our results showed that E₂-HP hydrogel can significantly facilitate the regeneration of injured endometrium along with inhibiting the cell apoptosis in IUA model. Furthermore, we revealed that E₂-HP hydrogel on the recovery of IUA was closely associated with the upregulation of kisspeptin through activating the ERK1/2 and MAPKs p38 pathways. In conclusion, E₂-HP hydrogel can effectively transfer E₂ into the injured endometrium and it can be considered as a promising therapeutic method for the women with intrauterine adhesions.