慢性难愈合创面是外科中难解决的治疗问题。已报道间充质干细胞（MSCs）修复创面效果显著，但存在创面炎症、缺血缺氧降低移植干细胞的存活和对创面修复效果的问题。前期结果显示小鼠尾静脉注射MSCs能延长异体移植皮肤的存活并可改善炎症，氧化苦参碱(OMT)具有抗炎、抗氧化应激和抗凋亡的细胞保护作用。为此提出OMT水凝胶负载胎盘间充质干细胞(PMSCs)协同修复创面的假说。课题组拟应用糖尿病缺血性皮肤溃疡小鼠模型、细胞炎症和血氧剥夺模型、3D表皮分化模型等技术，采用CRISPR/cas9基因敲除、过表达，TLR4/NF-κB和Nrf2/PINK1通路激活或阻断的方法，明确OMT协同PMSCs移植治疗难愈性创面的作用，阐明OMT抑制TLR4/NF-κB通路促进PMSCs免疫调节和活化Nrf2/PINK1介导的线粒体自噬改善移植PMSCs凋亡的机制，为OMT协同PMSC改善创面愈合的方法提供理论依据。

Chronic wound healing is a very serious problem and it also puzzle people in the long term. It had been reported that mesenchymal stem cells had obvious effect on wound healing，and Oxymatrine(OMT) has the protection effect of anti-inflammatory, anti-ischemic and anti-apoptosis on wound healing. However, pathological inflammation and extreme ischemic hypoxia can seriously threaten the survival of transplanted stem cells and hinder its function of tissue repair. We found that OMT hydrogel loading placental mesenchymal stem cells (pMSCs) helped to reduce the inflammatory, stress and apoptotic after pMSCs transplantation, but the mechanism was still unclear. According to literature and preliminary results，We propose the hypothesis: The OMT was proposed to inhibit the inflammation by TLR4/NF-kappa B, as well as, activating Nrf2/Pink1 induced autophagy. Oxymatrine promote PMSCs survival by the bidirectional regulation. We intends to adopt the in vitro and in vivo model, and apply viral mediated gene insertion and interference techniques, CRISPR/Cas9-mediated gene knockout, 3D epidermal differentiation model and other technologies. We will definite OMT improve pMSCs transplantation environment through antibacterial, anti-inflammatory. The mechanism of Oxymatrine pretreatment promoting the protection effect of placental stem cell transplantation on wound healing via TLR4/NF-κB and Nrf2/PINK1 pathway will help realize the transformation from clinical research to its clinical application. And it will proved the Oxymatrine and MSC treatment has a good effect on the repair and healing of skin chronic wound. It will provided theoretical basis and new ideas for for the treatment of skin wound and for further study on the mechanism of the repair and healing.