Therapeutic strategies: Bioactive hydrogels oxidized sodium alginate/strontium/betamethasone for preventing intrauterine adhesion

Intrauterine adhesion (IUA) is an endometrial damage repair disorder that leads to menstrual loss, amenorrhea, and infertility in women; therefore, addressing this dilemma is a critical challenge. In this study, a multifunctional hydrogel, comprising oxidized sodium alginate (OSA), strontium carbonate (SrCO 3 ), and betamethasone 21-phosphate sodium (BSP), was formulated to facilitate angiogenesis, reduce fibrosis, and support tissue repair in the treatment of IUA. The composite hydrogels showed significant bioactivity on human endometrial stromal cells (HESCs) and human umbilical vein endothelial cells (HUVECs), promoting the injured HESCs repair, reversing the degree of fibrosis to a certain extent, and enhancing the proliferation and migration of HUVECs. These results were also verified in the IUA model of sexually mature female rats. Compared with the model group, the selection of the appropriate hydrogel significantly increased endometrial thickness ( p  < 0.01), the number of glands ( p  < 0.001), decreased the degree of fibrosis ( p  < 0.05), and Vimentin ( p  < 0.01), CK19 ( p  < 0.01), CD31 ( p  < 0.01), and Ki67 ( p  < 0.01) molecular expression increased remarkably. In summary, in situ injection of this multifunctional hydrogel into the uterine cavity not only serves as a physical barrier, isolating the damaged endometrium, but also gradually releases drugs as the hydrogel degrades. This multifunctional hydrogel promotes endometrial proliferation and angiogenesis while reducing fibrosis, and provides therapeutic strategies for patients with clinical IUA.