Abstract：
Uterine scar was one of the long-term complications cesarean section. In this study, an thermo-responsive injectable hydrogel loaded with human umbilical cord mesenchymal stem cells (UCMSCs) and asiaticoside microspheres (AMs) was used for uterine scar repair, which was prepared by optimizing the mixed ratio of aldehyde-functionalized Pluronic F127 (F127-CHO) and adipic dihydrazide-modified hyaluronic acid (AHA). The asiaticoside was loaded in Poly (DL-lactide-co-gycolide) (PLGA) by emulsion- diffusion-evaporation method. The hydrogel had appropriate pore size, good mechanical property, and slow release ability of asiaticoside. In vitro cell experiments demonstrated that F127-CHO/AHA/AMs could effectively promote stem cell adhesion and proliferation, promote angiogenesis, and provide a suitable microenvironment for cell survival. The F127-CHO/AHA/AMs/UCMSCs hydrogel was further used to repair uterine scar in female SD rats. The results showed that the prepared hydrogel could promote the proliferation of rat endometrial cells, promote the regeneration of glands, reduce the degree of endometrial fibrosis and restore the morphology of uterine cavity. The hydrogel could upregulate expression of Ki67 and IGF-1, downregulate TGF-β1 expression and promote M1-M2 transition of macrophages. This study confirmed that the prepared hydrogel could be used as an effective transplantation strategy, which could be expected to achieve clinical transformation of uterine scar repair.
摘要：
瘢痕子宫是剖宫产术后远期并发症之一。在这项研究中,加载人脐带间充质干细胞（UCMSCs）和积雪草苷微球（AMs）的热响应可注射水凝胶用于子宫瘢痕修复，通过优化醛官能化的PluronicF127（F127-CHO）和己二酸二酰肼修饰的透明质酸（AHA）的混合比例制备。通过乳化-扩散-蒸发方法将积雪草苷装载在聚(DL-丙交酯-共-丙交酯)(PLGA)中。水凝胶具有适当的孔径，良好的机械性能，积雪草苷的缓释能力。体外细胞实验表明,F127-CHO/AHA/AMs能有效促进干细胞的黏附和增殖,促进血管生成，并为细胞存活提供合适的微环境。F127-CHO/AHA/AMs/UCMSCs水凝胶进一步用于修复雌性SD大鼠的子宫瘢痕。结果表明,所制备的水凝胶能促进大鼠子宫内膜细胞的增殖,促进腺体的再生，减轻子宫内膜纤维化程度,恢复子宫腔形态。水凝胶可以上调巨噬细胞Ki67和IGF-1的表达，下调TGF-β1的表达并促进M1-M2的转化。本研究证实，所制备的水凝胶可作为一种有效的移植策略，有望实现子宫瘢痕修复的临床转化。
