Incorporation Of Stromal Cell-derived Factor-1α In Silk Fibroin-bacterial Cellulose Membrane Promotes Regeneration Of Rat Uterine Injury

Objective:Intrauterine adhesions caused by curettage and severe infections, as well as scar formation followed by caesarean section may lead to infertility, miscarriages and other obstetrical complications, such as placenta previa, placenta accreta and etc. However, effective treatment to the repair and regeneration of uterine injury is still lack. Scar tissues, instead of native tissues often grow into the site of injury, and this affects tissue regeneration. This study aimed to develop a bioactive composite which can promote uterine cells migrate to injury site and participant in the repair and regeneration of uterine injury.Study design: Chemotactic effect of recombinant human stromal cell-derived factor-lα (rhSDF-lα) on rat uterine cells was. confirmed firstly. Meanwhile, silk fibroin-bacterial cellulose (SF-BC) membrane were obtained by culturing Acetobacter Xylinum (1.1812) in fermentation medium which contained silk fibroin. Then the membrane was soaked in100ng/ml rhSDF-la solution for12h at37℃. The obtained SF-BC membrane was evaluated in vitro for its cytotoxicity, effect on cell proliferation, cell morphology and protein release. Subsequently, effect of SF-BC membrane incorporated with rhSDF-la on the regeneration of injuried uterus was assessed in rat full-thickness uterine injury, then thickness of endometrium, percentage of endometrial stromal cells and arteriogenesis were assessed at30days and90days after surgery, also with pregnancy outcomes30days after surgery.Results:Recombinant human SDF-la (100ng/ml) significantly induced migration of rat uterine cells in vitro. Moreover, cytotoxicity test, cell proliferation assay and cell morphology observation demonstrated good biocompatibility of SF-BC membrane. And protein release assay suggested that SF-BC membrane could release protein for24hours. After the implantation of SF-BC membrane which was incorporated with rhSDF-la at the site of rat full-thickness uterine injury, the membrane promoted regeneration of uterine endometrium, as well as migration of endometrial stromal and epithelial cells to the injuried site, and improved arteriogenesis (30days and90days post implantation) at the injuried site. Furthermore, it also increased the number of fetuses of each injuried uterus30days after surgery (6.8±1.0).Conclusion:SF-BC membrane functionalized with rhSDF-lα facilitated recruitment of uterine cells and endometrium regeneration, also promoted arteriogenesis and ameliorated pregnancy outcomes of rat injuried uterus. The results indicate the potential for using SF-BC membrane loading with rhSDF-la as a bioactive scaffold for clinical application of uterine regeneration.