负载二甲双胍的可注射人牙周膜干细胞-磷酸钙骨水泥支架修复牙周组织及相关机制的研究

牙周组织缺损是正畸并发症之一，损害口腔和全身健康。种植牙周膜干细胞（hPDLSC）的组织工程支架是牙周组织修复的研究热点。目前多数研究将hPDLSC种植于支架表面，支架的组织修复能力受限。开发内部封装hPDLSC且机械强度良好的组织工程支架可增加组织修复效率。前期研究表明磷酸钙骨水泥（CPC）-藻酸盐水凝胶是能封装细胞且机械强度良好的可注射支架材料。研究还证明二甲双胍可促进hPDLSC的成骨向分化，然而二甲双胍摄取及作用机制未完全阐明。我们推测用CPC-藻酸盐水凝胶封装hPDLSC并将二甲双胍负载于支架，可构建高效、机械强度良好的可注射牙周组织工程支架。本项目拟评估负载二甲双胍的可注射hPDLSC-CPC支架的牙周组织修复能力，并探索有机阳离子转运蛋白和细胞外信号调节激酶1/2通路在二甲双胍调节hPDLSC成骨和成牙骨质过程中的机制。本项目将开发新型牙周组织工程支架，为牙周再生提供新思路。

Periodontal tissue defect, a complication of orthodontic treatment, will impair oral and general health. Tissue engineering scaffold seeded with human periodontal ligament stem cells (hPDLSCs) is a hot research point in periodontal tissue regeneration area. In most studies，hPDLSCs were seeded on the surface of scaffolds. This restricted the efficiency of scaffolds. Developing hPDLSC-encapsulating scaffolds with good mechanical strength will increase the efficiency of periodontal regeneration. Our previous study demonstrated that calcium phosphate cement (CPC)-alginate hydrogel can encapsulate seed cells and has proper mechanical strength. Our another study indicated that metformin can induce the osteodifferentiation of hPDLSC, but the mechanism of metformin intake and effect was not totally clarified. Thus, we infer that an effective and injectable periodontal tissue engineering scaffold with well mechanical strength can be formed if we use CPC-hydrogel to lade hPDLSC and add metformin into the scaffold. Our project aims to investigate the periodontal regeneration ability of injectable metformin-hPDLSC-CPC scaffolds. And we will also investigate the mechanism of organic cation transporter and extracellular signal-regulated kinase 1/2 signaling pathway in the process that metformin effects the osteogenic differentiation and cementogenic differentiation of hPDLSCs. This project will develop a new periodontal tissue engineering scaffold and provide novel ideas to periodontal regeneration.