基于光偶联反应原位构建微环境调控型真皮支架的实验研究

网络化微环境紊乱是慢性创面的基本特征，单靶点调控的治疗效果并不理想。我们前期研究构建了300–600μm大小的组织工程化活性微粒羊膜，发现其能多靶点主动调控慢性创面恶性微环境。由于缺乏合适的载体支撑，以局部涂抹的方式应用到创面后微粒羊膜易流失、不易存活。本研究拟以光偶联反应为交联机制、透明质酸和明胶为交联介质，低毒、可控地构建能原位成型并与组织强粘附的仿生水凝胶。以此为载体递送活性微粒羊膜，既保证创面局部获得高剂量、高活性的微粒羊膜，同时也为移植后细胞的存活提供仿生微环境。将进一步探索水凝胶成胶机理、对活性微粒羊膜功能调控，以及复合真皮支架修复慢性创面的效果和机制。本研究以光偶联反应技术及微型组织工程技术构建可原位成型及主动调控创面微环境的新型真皮支架，为慢性创面治疗提供新的方法。

The disorder of microenvironment network is the basic feature of chronic wound, and the therapeutic effect of single-target regulation is not ideal. In our previous study, we have constructed tissue-engineered living micronized amnion (LMAM) with the size of 300-600 μm, and found that LMAM could actively regulate the malignant microenvironment of chronic wound with multiple targets. Due to the lack of proper carrier support, LMAM is easy to be lost and not easy to survive when transplanted onto the wounds by locally smearing. In this study, photocoupling reaction is used as the cross-linking technology, hyaluronic acid and gelatin are used as the cross-linking matrix to construct biomimetic hydrogel with low toxicity, controllability, in-situ forming and strong adhesion to tissues. With this hydrogel as the carrier to deliver LMAM, it can not only ensure the high dose and high activity of LMAM delivered to wound, but also provide a biomimetic microenvironment for the survival of cells after transplantation. We will further explore the mechanism of hydrogel formation, the function regulation of hydrogel to LMAM, and the effect and mechanism of dermal scaffold repairing chronic wounds. This study intends to use photocoupling reaction and micro-tissue engineering technology to construct a dermal scaffold that can be formed in situ and regulate wound microenvironment actively, providing a new method for chronic wound repair.