纳米酶基因载体促进表皮干细胞增殖用于慢性皮肤创面组织再生修复及机制研究

皮肤创面组织再生修复的有序调控与干预是当前研究的热点和难点。表皮干细胞（EpSCs）的数量和增殖能力不足是导致创面迁延不愈的最重要的原因之一。慢性创面高氧化应激和持续炎症的微环境，是导致EpSCs增殖能力受损的重要原因。因此，基于修复再生机制，设计新型生物材料，促进EpSCs增殖，形成经激活内源性再生能力与调控微环境，有望实现慢性创面原位再生修复。我们课题组研究发现，P311参与创面修复的整个过程，是调控EpSCs增殖的新分子。基于此，我们创新性的设计了搭载P311表达质粒的超小铜纳米酶，通过清除过量ROS降低氧化应激，减轻炎症，重塑有利于EpSCs增殖的微环境，同时通过基因治疗提供大量P311刺激EpSCs增殖；探索其可能的关键促进组织再生的通路Wnt/P38 MAPK-JNK-cJun。本项目的完成将为后续慢性创面的临床治疗，提供一种新的促进皮肤组织有序再生修复的干预靶点和手段。

The orderly regulation and intervention of skin wound tissue regeneration and repair is the hotspot and difficulty of current research. The insufficient number and proliferation of epidermal stem cells (EpSCs) is one of the most important reasons for the delayed wound healing. The high oxidative stress and persistent inflammation microenvironment of chronic wound are the most important reasons for the impaired proliferation of EPSCs. Therefore, based on the mechanism of repair and regeneration, new biomaterials are designed to promote the proliferation of EpSCs and form an activated endogenous regeneration ability and regulatory microenvironment, which is expected to realize the in situ regeneration and repair of chronic wounds. Our research group found that P311 participates in the whole process of wound repair and is a new molecule regulating the proliferation of EpSCs. Based on this, we innovatively designed an ultrasmall copper nanoenzyme carrying P311 expression plasmid to reduce oxidative stress, alleviate inflammation, reshape the microenvironment conducive to the proliferation of EPSCs, and provide a large number of P311 to stimulate the proliferation of EPSCs through gene therapy, and further explore its possible key pathway Wnt/p38 MAPK-JNK-cJun to promote tissue regeneration. The completion of this project will provide a new intervention target and means to promote the orderly regeneration and repair of skin tissue for the follow-up clinical treatment of chronic wounds.