PAF26抗菌肽自组装水凝胶伤口敷料的制备与性能研究

Wound infection is the primary factor that affects wound healing. An important measure to prevent wound from infection is using wound dressings with antimicrobial function. However, the antimicrobial safety and efficiency of existing wound dressings are not satisfied. Therefore, in this project wound dressing based on the self-assembled antibacterial peptide will be studied. Antimicrobial peptide is a kind of antibacterial agent with broad spectrum antimicrobial activity, low drug resistance and good biocompatibility. Based on the amphipathic structure of antimicrobial peptide and the self-assembly property of amphipathic peptide, the antimicrobial peptide hydrogel for wound dressing will be synthesized. In this project, the PAF26 antimicrobial peptide and its derivatives will be designed and synthesized by solid-phase method. Then their ability of self-assembly into hydrogels will be evaluated, and the molecule structure of PAF26 derivatives will be optimized according to the rheology, transmission electron microscopy and circular dichroism experiments. Subsequently, the antimicrobial ability, antimicrobial mechanism and biocompatibility of the self-assembled hydrogels will be studied, and the effect of molecule structure of PAF26 derivatives on antimicrobial ability of the self-assembled hydrogel will be investigated. Finally, the effects of antimicrobial peptide hydrogel on wound healing and infection in vivo will be evaluated by establishing skin wound mode. In this project, it is expected that hydrogel wound dressing formed by self-assembled antimicrobial peptide with outstanding antimicrobial ability and biocompatibility will be discovered. Moreover, this project will provide a novel thought and method for the application of antimicrobial peptide in wound dressing.

伤口感染是阻碍伤口愈合的首要原因，使用具有抗菌性能的伤口敷料是避免伤口发生感染的重要措施。针对现有伤口敷料缺乏安全、高效抗菌能力的问题，本项目拟选用具有广谱抗菌活性、低抗药性和良好生物相容性的抗菌肽，利用其两亲性结构特点进行自组装，进而实现抗菌肽水凝胶伤口敷料的制备。本项目首先采用固相合成的方法制备PAF26抗菌肽及其衍生物，研究其自组装形成水凝胶的能力，并结合流变学、透射电子显微镜、圆二色谱等分析手段对PAF26衍生物进行分子结构优化；然后研究抗菌肽水凝胶的抗菌性能、抗菌机制以及生物相容性，并结合结果探讨PAF26衍生物的分子结构设计对抗菌肽水凝胶抗菌性能的影响；最后通过构建皮肤创伤小鼠模型，对抗菌肽水凝胶在体内促进伤口修复和伤口抗菌的效果进行评估。本研究有望得到具有优异抗菌性能和生物相容性的抗菌肽水凝胶伤口敷料，为抗菌肽在伤口敷料中的应用提供新的思路和方法。

伤口感染会严重阻碍伤口愈合的速度和进程。抗菌水凝胶作为一种新型伤口敷料，能够避免伤口感染和加快伤口愈合，具有巨大的应用前景。本项目以具有广谱抗菌活性、低抗药性和良好生物相容性的PAF26抗菌肽为基础，利用分子自组装技术制备抗菌肽水凝胶，并围绕“两亲性多肽自组装形成水凝胶的结构设计规律、抗菌肽水凝胶的抗菌机理”等科学问题进行研究。多肽自组装行为和机理研究表明，多肽分子中亲疏水性氨基酸的数量、碱性氨基酸的静电斥力、酸性氨基酸与碱性氨基酸的静电引力、分子间的共价交联等都会影响多肽的自组装行为；多肽自组装水凝胶的抗菌性能和抗菌机理研究表明，大多数抗菌肽水凝胶具有良好的接触性抗菌效果，但扩散性抗菌效果与抗菌肽的溶解性和自组装体的交联程度有关。本项目研究为抗菌肽水凝胶的设计和制备提供了参考。