Genetically engineered FGF1-sericin hydrogel material treats intrauterine adhesion and restores fertility in rat

Abstract

Endometrial injury can cause intrauterine adhesions (IUA) and induce the formation of endometrial fibrosis, leading to infertility and miscarriage. At present, there is no effective treatment method for severe IUA and uterine basal injury with adhesion area larger than 1/3 of the uterus. In this study, we prepared FGF1 silk sericin hydrogel material (FGF1-SS hydrogel) to treat endometrial injury and prevent endometrial fibrosis. Compared with the silk sericin hydrogel material (WT-SS hydrogel), FGF1-SS hydrogel significantly promotes the cell migration and infiltration ability of endometrial stromal cells (ESCs). More importantly, FGF1-SS hydrogel can release FGF1 stably for a long time and inhibit The ESCs injury model forms fibrosis through the TGF-β/Smad pathway. In the IUA rat model, FGF1-SS hydrogel treatment effectively restored the number of uterine glands and uterine wall thickness in rats, with a fertility rate of 65.1 ± 6.4%. The results show that FGF1-SS hydrogel is expected to be a candidate to prevent IUA.

Fibroblast growth factor 1 ameliorates thin endometrium in rats through activation of the autophagic pathway

“…The main cause of endometrial fibrosis is now considered to be abnormal migration and proliferation of uterine epithelial and mesenchymal cells, leading to abnormal secretion of extracellular matrix proteins and cytokines, resulting in the deposition of type I collagen in the endometrium to form endometrial fibrosis ( Hu et al, 2018 ; Cao et al, 2020 ). In the present study, FGF1 inhibited endometrial fibrosis, a result that was consistent with the earlier finding of Guan et al ( Guan et al, 2022 ) that hydrogel-bound FGF1 suppressed the process of intrauterine endofibrosis.…”

“…While FGF1 has been studied in the past for its role in fat metabolism and diabetic wounds ( Wang et al, 2020a ; Deptula et al, 2021 ), its use in skin repair has also been reported in recent years ( He et al, 2019 ). In addition, Guan et al ( Guan et al, 2022 ) found that FGF1 combined with hydrogel could be used to treat intrauterine adhesions. On this basis, we hypothesized that FGF1 could promote endometrial thickening and facilitate recovery of endometrial function.…”

Melatonin-pretreated human umbilical cord mesenchymal stem cells improved endometrium regeneration and fertility recovery through macrophage immunomodulation in rats with intrauterine adhesions

“…An important consequence of IUA is secondary fibrous tissue proliferation in the uterine cavity with partial or complete occlusion [48]. The prevalence of IUA in women ranges at 2–22% and affects female fertility [49].…”

Bioengineering approaches for the endometrial research and application

“…Drug-loaded hydrogels and porous microfluidics allow for the combination of multiple therapeutics owing to their potent encapsulation capability, alleviating postoperative IUAs and improving endometrial repair [ 151 , 152 ]. Embedded active proteins and estrogen in bio-scaffolds endow them with antioxidant properties that protect against fibrosis within the uterine cavity and encourage the self-repair of the remaining endometrial cells by downregulating excessive oxidative stress and fibrosis-related mediators [ [153] , [154] , [155] , [156] , [157] ]. Administration of both SCs and their derivatives, such as human umbilical cord mesenchymal SCs (UCMSCs), mesenchymal SCs (MSCs), apoptotic bodies, and secretomes, in hydrogels and acellular scaffolds also potentially contribute to satisfactory endothelial regeneration after IUA [ [57] , [158] , [159] ].…”