现有组织工程皮肤存在机械强度不足和角质形成细胞（KCs）迁移及增殖能力差等缺陷，限制了其临床应用。我们前期研究发现脂肪干细胞（ADSCs）可促进KCs的迁移和增殖，且ADSCs可以旁分泌大量MMP-1；而纳米仿生支架负载生物活性分子或者改变拓扑结构及理化特性可明显影响细胞的生物学行为。基于此，项目组拟深入研究ADSCs通过旁分泌MMP-1促进KCs增殖和迁移的机制，并筛选出发挥重要作用的关键分子；研究支架材料的拓扑结构和理化特性对ADSCs、KCs的细胞生物学行为的影响；根据ADSCs促进KCs迁移和增殖的研究结果，于支架材料内负载MMP-1或其下游发挥作用的关键活性分子，利用细胞层层叠加自组装的技术构建复层活细胞仿生人工皮肤，并在裸鼠皮肤缺损模型验证其修复功能。本项目可进一步揭示ADSCs对KCs的调控机制，并有望成功构建新型组织工程皮肤，具有重要理论及临床意义。

The main defect of the present tissue engineering skin including insufficient mechanical strength and poor migration and proliferation ability of KCs has limited its clinical application. The literature and our previous study found that adipose derived stem cells (ADSCs) could promote the migration and proliferation of KCs, but its mechanism still remained unclear. Besides, the nanofibrous scaffold with incorporating bioactive molecules or varying topological structure and phychemical properties could significantly influence the biological behavior of the cells, but there is no research on the regulation of KCs through directly regulating by nanofibrous scaffold or through ADSCs with scaffold. Based on this, the team proposed that the scaffold prepared by phychemical and biological modification is expected to directly regulating the proliferation and migration of KCs or through ADSCs, and further construct a novel tissue engineering skin which could be clinically applied. This project intends to further study the molecular mechanism in which ADSCs regulate the migration and proliferation of KCs, and accordingly incorporate bioactive molecules which could promote the function of KCs in combination with the topology structure and the phychemical and biological modification of nanofibrous scaffold to directly promote proliferation and migration of KCs or through ADSCs, and then fabricate novel tissue engineering skin via layer-by-layer technique and verify its effect on wound repair within skin defect model of nude mice. This project can further reveal the mechanism in which ADSCs could regulate the biological behavior of KCs, and successfully construct a novel tissue engineering skin which has important theoretical and clinical significance.