自收缩microRNA21高转染促伤口愈合多功能水凝胶的构建及机制研究

全层皮肤损伤是最常见的医疗健康问题，当前治疗和研究多将功能因子加入敷料中促进伤口愈合，但仍存在愈合慢、易感染及生成瘢痕等问题。胚胎伤口修复已证实，伤口前沿肌动蛋白环收缩可拉动伤口闭合并防止瘢痕形成。而成人皮肤收缩能力明显降低，且皮肤生物力学活性对创面修复的影响通常被忽略，这可能是造成现有敷料修复效果不佳的原因之一。受此启发，我们提出一种自收缩microRNA21高转染促伤口愈合多功能水凝胶，利用材料温敏性收缩和强氢键作用，模仿胚胎伤口修复机制，在皮肤表面产生收缩力，牵引伤口闭合。同时，可控释放基因纳米粒在细胞内产生独特的“二氧化碳纳米炸弹”效应和蛋白酶特异性解离释放基因功能，microRNA21高效转染促进细胞迁移和再上皮化。目标水凝胶的机械收缩促动力和细胞迁移促动力的协同增效有望实现伤口的快速无瘢痕愈合并揭示其修复机制，为解决难愈合伤口的快速修复提供新材料和新策略。

Full-thickness skin injury is the most common medical and health problem. Clinical treatment options and the researches focus on adding a variety of biochemical functional factors to dressings to promote wound healing. However, the desirable effect still has not be achieved, facing the problems of long periods of wound healing, susceptible to be infected and scar formation. It has been clearly confirmed in embryonic wound healing that the formation of actin cables at the leading edge of the wound can effectively contract the wound to closure without scar formation. In contrast, the postnatal skin of the adult human exhibits substantially less contraction and the effect of skin biomechanical force on wound healing has been largely ignored. This may be one of the reasons for the poor healing effect of the existing dressing. Inspired by this phenomenon, here we proposed a new type of self-contraction microRNA nanoparticle composite hydrogel. The biomimetic hydrogel dressing is constructed with keratin and chitosan. The temperature-sensitive contraction of the material and the strong hydrogen bond effect are used to imitate the healing of embryonic wounds, generating contraction force on the skin and pulling the wound to close. At the same time, the controlled release of microRNA nanoparticles, with its unique "CO2 nano bomb" and enzyme-triggered degradation, improve the transfection efficiency. The therapeutic microRNA could effectively promote granulation tissue formation and re-epithelialization. The synergistic effect of the external mechanical contraction actuation and internal cell migration actuation is expected to effectively accelerate wound closure and scar-free wound healing and reveal the repair mechanism，thus providing new materials and a new strategy for effective therapy of difficult-to-heal wounds.