Abstract: BACKGROUND: Studies have shown that treatment with exosomes and miR-424-5p mimics can promote angiogenesis and ameliorate endometrial injury. However, it is difficult for exosomes to attach to the endometrial wall after intrauterine administration, which shortens the retention time of exosomes and results in the inability of exosomes to fully exert their biological effects. Therefore, in recent years, more and more biological scaffolds have been used to deliver exosomes, so that exosomes can continue to play biological effects at the injured site.
OBJECTIVE: To observe the effect of miR-424-5p modified exosome/Poloxam 407 hydrogel on the proliferation, migration, and angiogenesis of human umbilical vein endothelial cells, as well as the therapeutic effect on endometrial injury in rats. 
METHODS: miR-424-5p was transfected into rat bone marrow mesenchymal stem cells by lentiviral transfection, and exosomes were subsequently extracted from bone marrow mesenchymal stem cells and identified. The expression of miR-424-5p in exosomes not transfected with lentivirus, exosomes transfected with lentivirus, and exosomes transfected with empty vector were detected by RT-qPCR to verify the transfection success. Poloxam 407 hydrogel, exosome/Poloxam 407 hydrogel, and miR-424-5p modified exosome/Poloxam 407 hydrogel were prepared respectively, and cell proliferation, migration, and capillary network formation were detected after co-culture with human umbilical vein endothelial cells. A total of 35 SD rats were randomly divided into sham operation group, model group, hydrogel group, non-transfected exosome hydrogel group, and transfected exosome hydrogel group, with 7 rats in each group. Except the sham operation group, endometrial injury models were established in the other four groups and corresponding hydrogel treatment was given, while no treatment was given in the model group. At 14 days after operation, samples were collected. The morphologic structure, angiogenesis, and receptivity indexes of endometrium were detected.
RESULTS AND CONCLUSION: (1) In vitro cell experiment results showed that both exosome/Poloxam 407 hydrogel and miR-424-5P-modified exosome/Poloxam 407 hydrogel could promote the proliferation, migration, and capillary network formation of human umbilical vein endothelial cells, and the promotion effect of miR-424-5p-modified exosome/Poloxam 407 hydrogel was more significant. (2) Animal experiments showed that exosome/Poloxam 407 hydrogel and miR-424-5p modified exosome/Poloxam 407 hydrogel could increase the thickness and number of glands of the injured endometrial, inhibit fibrosis, promote the formation of blood vessels, and the expression of tolerance indicators, and have a good therapeutic effect on endometrial injury. Moreover, miR-424-5p modified exosome/Poloxa 407 hydrogel had a more significant therapeutic effect. These findings conclude that miR-424-5p modified exosome/Poloxam 407 hydrogel can promote tissue regeneration, angiogenesis and improve receptivity of injured endometrium in rats by promoting the proliferation, migration, and angiogenesis of human umbilical vein endothelial cells, thus playing a potential therapeutic role. 

Key words: exosome, hydrogel, lentivirus transfection, Poloxam 407, endometrial injury, human umbilical vein endothelial cell