仿贻贝葡聚糖基高效止血抗菌材料的设计合成及其止血机理研究

Due to the problem of poor adhesion property, limited hemostatic function, high price, and poor biosafety in moderate and severe bleeding hemostatic materials, further development of new hemostatic materials for bleeding is urgently required. Based on the fact that both catechol derivatives and lysine synergistic structures have a strong wet adhesion similar to the mussels’ byssus protein, and that dextran has the function of strong water absorption, antibacterial effect, and wound healing, in this application, the synergistic structure of polyphenol compound and lysine is introduced into the dextran group to create a new, safe, fast and antibacterial hemostatic materials using for uncontrolled hemorrhage, and to improve its adhesion property and hemostatic effects..In order to improve grafting ratio of dextran derivatives and effectively synthesize a series of new mussel-inspired hemostatic materials, this project tries to introduce the different polyphenol compound and the lysine into the dextran by molecular design. By studying the structure-activity relationship between molecular structure and functions of wet adhesion and hemostatic performance, the mechanism of hemostasis is explored. By means of strong wet adhesion for sealing wound and high concentrated coagulation factor, the purpose of high efficiency, high speed, and safe hemostasis can be achieved, and the number of deaths caused by bleeding can be greatly reduced. This proposal can provide an experimental basis and theoretical guidance for creating new hemostatic materials for moderate and severe bleeding.

本申请针对中重度出血止血材料存在的湿黏附性差、止血作用有限、价格昂贵、生物安全性差的问题，基于含有邻苯二酚结构的衍生物及赖氨酸协同结构，均具有类似贻贝分泌的足丝蛋白的超强黏附性，以及葡聚糖具有强吸水、抗菌与促伤口愈合功能的认识，本申请提出将多酚化合物和赖氨酸协同增效结构引入葡聚糖母体的构思，创新一类湿黏附性好、止血功能强的不可控出血急救用快速、安全止血抗菌材料。通过分子设计，有目的地引入不同多酚化合物-赖氨酸结构，提高其与葡聚糖衍生物的接枝率，高效合成系列仿贻贝葡聚糖基新型止血抗菌材料。在此基础上，深入研究分子结构与湿黏附性、止血性能的构效关系，探明止血机理，实现强湿黏附密封伤口、高度浓缩凝血因子，达到不可控出血高效、快速、安全止血的目的，大大降低可避免出血死亡的人数，为中重度出血止血新材料的创制提供实验和理论依据。

针对中重度出血的止血，本项目设计并合成了一类具有良好降解性、抗菌性能的聚多巴胺/二氧化硅纳米多孔材料，和一类多功能醛基葡聚糖海绵材料。基于对材料结构和湿黏附性、抗菌及促伤口愈合的构效规律，探究了材料具有该湿黏附性高、抗菌与促伤口愈合效果的原因；通过SD大鼠和兔的中重度止血模型，证明了PDA/SiNP和DA海绵材料优良的止血性能，并通过分析凝血四项和采用血栓弹力图，对材料的止血机理进行深入地探索，阐明新止血体系的凝血机理，即酚羟基、氨基官能团及适当的疏水性利于血细胞聚集和诱导凝血。最后通过生物相容性，证实了系列材料潜在的应用价值。在后续研究中，将优化所制备的止血材料，拟计划通过复配羟基磷灰石、蒙脱土等材料进一步强化材料的止血性能。研究工作共发表6篇论文，授权专利2项，参加两次国内外会议。