诱导皮肤再生的抗感染和促血管化水凝胶支架的构建

Skin loss caused by trauma, burn and chronic diseases has become a big burden for both social medical service and personal quality of life. Tissue engineering and regenerative medicine have afforded many solutions for skin repair, but infection and slow angiogenesis are compounding difficulties of skin repair and regeneration. In this project a new skin repair system has been proposed aiming at high infection rate and slow angiogenesis. Firstly, antimicrobial peptides (AMP) can be immobilized onto the surface of dextran (Dex), and then fabricate anti-infection hydrogels, evaluate their antimicrobial activities and the effects on biofilm formation. Then, gene therapy has been used by incorporation of vector/DNA particles into anti-infection hydrogels to construct a composite system in order to achieve anti-infection and promotion of angiogenesis simultaneously. Finally, the repair ability of skin has been evaluated by infected burn-wound in the rat model. In this study AMP have been firstly incorporated into anti-infection tissue engineering scaffolds, taken together infection and angiogenesis, hope to obtain better repair results, and then provide new solution and theory for management of compound wounds.

皮肤缺损给社会医疗体系和个人生活质量带来很大负担。虽然组织工程和再生医学为缺损修复提供了新的思路，但感染和新生组织血管化速度慢且血管化程度不高的问题使得皮肤缺损创面的修复再生更加困难。本项目针对皮肤缺损创面感染率高和血管化慢两大难题，提出构建具有抗感染和促进快速血管化的皮肤缺损修复复合体系。首先，本研究采用抗菌肽修饰葡聚糖，构建具有抗感染功能的水凝胶支架，系统研究抗感染水凝胶对致病菌的杀菌能力和生物膜形成的影响；然后引入基因治疗的手段，将载体/质粒DNA粒子负载到抗感染水凝胶上，同时达到抗感染和促进血管化的功效，并在大鼠深度烧伤感染创面原位评价复合体系对皮肤缺损的修复能力。本研究首次采用抗菌肽构建具有抗感染功能的组织工程支架，综合考虑皮肤缺损修复中的两大因素：感染和血管化，有望取得更好的修复效果，同时为复杂创面的治疗提供新的思路和理论依据。

皮肤缺损给社会医疗体系和个人生活质量带来很大负担。虽然组织工程和再生医学为缺损修复提供了新的思路，但感染和新生组织血管化速度慢且血管化程度不高的问题使得皮肤缺损创面的修复再生更加困难。本项目针对皮肤缺损创面感染率高和血管化慢两大难题，提出构建具有抗感染和促进快速血管化的皮肤缺损修复复合体系。主要研究内容包括1、构建了负载抗生素（万古霉素、硫酸庆大霉素、姜黄素）的具有抗感染功能的支架；2、构建了负载血管生长因子（bFGF）的具有促血管化功能的支架；3、构建了同时负载姜黄素和血管生成素质粒DNA的具有抗感染和促血管化的支架；4、对上述支架进行了系统的体外和体内评价。本项目的一系列研究均取得了较好的成果，首次制备了纳米微晶纤维素（CNCs）增强的胶原基支架，自2014年发表以来已被引用17次，且被整段介绍（Biomacromolecules, 2014, 15 (7), 2327-2346.）。负载bFGF明胶微球的纳米微晶纤维素/胶原复合支架，被主编评价为很出色的研究。将姜黄素明胶微球负载到纳米微晶纤维素/胶原复合支架用于大鼠烧伤感染创面的修复取得了较好的结果（Journal of Tissue Engineering and Regenerative Medicine. DOI: 10.1002/term.2272.）。将bFGF海藻酸微球负载到CMCS/PVA水凝胶上用于大鼠烧伤创面的修复取得了较好的效果（Journal of Tissue Engineering and Regenerative Medicine. DOI: 10.1002/term.2057.）。分别选择盐酸万古霉素和硫酸庆大霉素作为抗菌剂，采用明胶微球作为药物运输的载体。制备出抗生素/明胶微球/丝素蛋白复合支架，体外抗菌实验可知，该复合支架具有良好的抗菌性能（Journal of Biomaterials Science: Polymer Edition, 2014; 25(1):75-87）。大鼠烧伤感染创面进行了体内修复效果评价（Acta Biomaterialia, 2014, 10(7): 3167-76.）。将姜黄素和血管生成素质粒DNA（pDNA-ANG）同时负载到CNCs/PLGA电纺支架上，对支架进行了系统的体外和体内评价，相关结果已被Tissue Engineering接收。