壳聚糖基抗菌大分子的制备及其促进慢性伤口愈合的研究

Bacterial inhibition and wound epithelization are key points for the curation of chronic wounds. In this project, we propose to take advantage of the broad-spectrum antibacterial property and the epithelization capacity of the natural polysaccharide chitosan, by grafting poly(ε-lysine) onto chitosan through ring-opening polymerization, to prepare antibacterial agents behaving both high antibacterial efficiency and excellent epithelization capacity, and further construct novel wound dressing for chronic wounds therapy. The cationic/hydrophobic balance can be well controlled by tuning the density and length of poly(ε-lysine) side chain. The effect of side chain density and length on the antibacterial efficiency, epithelization capacity and hemolysis will be systematically investigated. The antibacterial mechanism will be further studied by bacterial morphology, membrane potential and protein analysis. In addition, the diabetic model rats will be applied to investigate the therapeutic effects of the antibacterial macromolecules on chronic wounds. This project aims to solve the problems between bacterial infection and wound epithelization, which may provide novel practice and theory for the therapy of chronic wounds.

杀灭抑制伤口有害菌群、促进创面上皮化是治疗慢性伤口的两大挑战。本项目以兼具广谱抗菌性能和促进创面上皮化能力的天然高分子壳聚糖为研究对象，通过开环聚合反应，在其分子上引入抗菌性多肽ε-聚赖氨酸侧链，构建既能高效杀灭有害菌群又能促进创面上皮化的天然高分子基抗菌剂，并开发用于治疗慢性伤口的新型伤口敷料。通过调节ε-聚赖氨酸的侧链密度、侧链长度，实现对抗菌大分子阳离子/疏水平衡的调控。研究侧链密度、侧链长度对大分子抗菌性能、促上皮化性能、以及溶血性能的影响规律。通过细菌形态学、细菌膜电位、细菌蛋白分析研究其抗菌机理，并以糖尿病模式大鼠为模型，进一步探讨抗菌大分子及其构建的新型敷料对慢性伤口的治疗作用。本项目以解决伤口细菌感染与促进创面上皮化为出发点，将为慢性伤口的治疗提供新的实验及理论依据。

细菌感染并形成生物膜导致伤口持续发炎而难于上皮化是伤口愈合的一大难题。本项目以兼具抗菌性和良好生物相容性的天然多糖壳聚糖为基体，通过化学改性的方法，在壳聚糖分子链上接枝亲水性聚乙二醇侧链和具有抗菌活性的功能基团和分子侧链，如胍基、设计的抗菌肽LK13和天然抗菌肽ε-聚赖氨酸，从而在保持壳聚糖生物相容性的前提下，增强其水溶性和抗菌性能，进而将其应用于动物伤口感染模型，研究其抑制感染并促进伤口愈合的性能。研究结果表明，结构独特的壳聚糖接枝物具有优异的穿透生物膜并抗菌的性能和促进感染伤口愈合的性能，作为急慢性感染伤口敷料用材料具有广阔的应用前景。本项目的开展为设计新型抗感染和促愈合生物医用材料提供了方法和理论依据。