【作者】 张晶；

【导师】 姜秀云； 王会岩；

【作者基本信息】 吉林农业大学 ， 微生物学， 2020， 硕士

【摘要】 卫生保健相关感染是世界上主要的公共卫生问题,因卫生保健引起的感染导致严重的后果,如经济负担加重,患者发病率和死亡率增加等。目前临床解决这类问题的主要方法是抗生素疗法,尽管抗生素的使用大大降低了细菌感染所造成的发病率和死亡率,但是细菌耐药性的产生已经严重威胁到病人的生命健康。新型抗菌剂的研究,为解决抗生素的耐药性提供了新思路。但新型抗菌剂如季铵盐、抗菌肽等的直接使用会产生严重的生物毒性。因此,在材料表面构建智能响应抗菌策略,一方面可以根据周围环境的变化实现相应功能的切换,另一方面可以维持材料良好的生物相容性。本论文针对日趋严重的材料细菌感染问题,开发抗细菌感染表面。尽管现有的抗菌表面具有优异的抗菌性能,但依然存在抗粘附和杀菌功能相互干扰,智能释放表面侧重于释放杀菌过程,无法解决非感染状态下表面的生物相容性等问题。因此本文构建了智能响应型抗菌体系,实现了抗菌和生物相容的按需启动,为拓展响应型抗菌表面的研究提供了新思路。第一部分:细菌激活型抗菌表面的构建及其性能研究在该研究中,通过紫外接枝的方法构建表面,将蜂毒肽固定于表面,随后将电荷转换机制引入到抗菌表面的设计中。利用傅立叶红外光谱、水接触角等检测表面构建成功。通过细菌实验证明,针对金黄色葡萄球菌杀死率约为94.16%,大肠杆菌的杀死率约为97.46%。通过生物相容性实验证明,表面暴露蜂毒肽的溶血率约为8.69%,经过电荷反转分子修饰后表面的溶血率约为0.56%;体内组织相容性的研究未发现引起体内组织的验证感染,并且体内抗菌性也达到90%以上。第二部分:p H响应的自适应型抗菌表面的构建及其性能研究本研究通过光引发接枝聚合反应将季铵化合物和p H敏感单体2,3-二甲基马来酸酐固定在表面,成功构建p H响应的自适应型抗菌表面。利用傅立叶红外光谱、水接触角等检测表面构建成功。通过细菌实验证明,针对金黄色葡萄球菌的杀菌率约为99.32%,抗粘附性达到90%。通过生物相容性实验证明,表面的溶血率0.26%,几乎不破坏血细胞形态,而且对体内的组织和抗菌性均显示出优异的性能。更多还原

【Abstract】 Health care-associated infections are the world’s major public health problems and lead to serious consequences,such as increased economic burden,increased patient morbidity and mortality.At present,the main method for solving such problems in clinical is antibiotic therapy.Although the use of antibiotics has greatly reduced the morbidity and mortality caused by bacterial infections,the emergence of bacterial resistance has seriously threatened the lives of patients.The study of new antibacterial agents provides new ideas for solving antibiotic resistance.However,the direct use of new antibacterial agents such as quaternary ammonium salts,antibacterial peptides will produce serious biological toxicity.Therefore,constructing an intelligent response antibacterial strategy on the surface of the material,on the one hand,can realize the corresponding function switching according to the changes of the surrounding environment,on the other hand,it can maintain the good biocompatibility of the material.This paper aims at the increasingly serious problem of bacterial infection of materials,and develops anti-bacterial infection surface.Although the existing antibacterial surface has excellent antibacterial properties,there are still anti-adhesion and sterilization functions that interfere with each other.The intelligent release surface focuses on the release sterilization process,which cannot solve the problem of surface biocompatibility under non-infected conditions.Therefore,this paper builds an intelligent responsive antibacterial system,which realizes the on-demand activation of antibacterial and biocompatibility,which provides new ideas for expanding the research of responsive antibacterial surfaces.Part I: Construction and properties of bacteria-activated antibacterial surfaces.In this study,the surface was constructed by UV grafting,the bee venom peptide was fixed to the surface,and then the charge conversion mechanism was introduced into the design of the antibacterial surface.The detection surface was successfully constructed using Fourier infrared spectroscopy and water contact angle.Bacterial experiments proved that the killing rate against Staphylococcus aureus(S.aureus)was about 94.16 %,and the killing rate of Escherichia coli(E.coli)was about 97.46 %.The biocompatibility experiment proved that the hemolysis rate of the surface exposed bee venom peptide was about 8.69 %,and the surface hemolysis rate after modification by charge reversal molecules was about 0.56 %;in vivo tissue compatibility studies did not find any Verification of infection,and antibacterial properties in vivo also reached more than 90%.Part II: The construction and performance of p H response adaptive antimicrobial surfaces.In this study,photoinitiated graft polymerization was used to fix the quaternary ammonium compound and the p H-sensitive monomer 2,3-dimethylmaleic anhydride on the surface,and a p H-responsive adaptive antibacterial surface was successfully construct.Using fourier infrared spectroscopy,water contact angle and so on detect the surface.Experiments show that the sterilization rate against S.aureus is about 99.32 %,the anti-adhesion rate reaches 90 %,the surface hemolysis rate is 0.26 %,almost does not destroy the blood cell morphology,and shows excellent tissue and antibacterial properties in the body performance.更多还原