基于相互感知作用的智能抗菌高分子材料研究

It is important to develop new generation of antimicrobial materials that are highly efficient, long lasting, safe and widely applicable. Based on our previous research on stereochemically triggered antibacterial adhesion, in this project, we propose a new type of smart antimicrobial polymer system, through combining antimicrobial terpenoids and microbicidal polymers, chitosan for example, with the use of dynamic covalent bonds, which may gradually response to the acidic substances in different periods of bacterial physiological actions. This smart polymer system realizes antimicrobial activities through the mutual sensing between microbes and material surface. There are three stages: firstly, microbes are known to have “stereochemical taste” on sensing external surface, which will determine if they will attach the surface; secondly, once microbes adsorb on the polymer surface or attempt to attach on it, smart polymer could sense bacteria attachment and kill the attached bacteria effectively through releasing terpenoids; finally, after gradually releasing terpenoids, the microbicidal polymers will be activated and released to kill the microbes, so biofilms should be unable to develop on the surface, thus eliminating the threat of microbes. For the construction of this smart polymer system, both small molecules and polymers, each bears two kinds of antimicrobial functions, are linked by dynamic covalent bonds. In addition, in this smart antimicrobial system, no additional carrier is used. It does not depend on any external force and does not release without sensing the microbes. Considering their intelligent responsive properties, this smart polymer system may exhibit many advantages, such as easy synthesis, biocompatibility, broad and lasting antimicrobial activities, and safe to use in medical devices and articles. Study on the structure-activity relationship will not only gain further insight in the antimicrobial theory, but also establish a foundation for biomedical clinical applications.

发展既高效持久又安全普适的新型抗菌材料和抗菌策略意义重大。基于本课题组在手性抗污领域的前期研究，本项目计划利用动态共价键，将抗菌萜类小分子和杀菌高分子相结合，构建新型的智能抗菌高分子体系，通过材料与细菌相互感知和自发响应实现抗菌。在这种抗菌体系中，细菌感知材料表面萜类立体化学信号，不与其粘附（抗粘附）；而材料感知细菌的接触会释放萜类分子杀菌（接触杀菌），并进一步释放杀菌高分子（释放杀菌），达到协同抗菌的效果。在材料构建上，小分子和高分子分别具有两种功能，各自在成键时抗粘附而断键时杀菌。该体系利用动态共价键将不同抗菌机制有机结合在一起，完成抗菌材料的智能化全利用，且无附加载体、不依赖外场、不主动释放。该策略使抗菌智能化，高效持久且易于实施，通过揭示智能高分子抗菌的构效关系，既可为抗菌理论的研究提供新思路，也为生物医学应用奠定基础。

发展既高效持久又安全普适的新型抗菌材料和抗菌策略意义重大。本课题组创新并发展了手性高分子抗菌材料，提出了立体化学抗菌策略，并从基础理论走向实际应用。该项目利用动态共价键，将萜类小分子和天然高分子相结合，构建了新型的智能抗菌高分子体系，通过材料与细菌在界面的相互感知和自发响应实现抑制菌粘附和响应性杀菌特性。项目筛选了两种有效萜类分子及三种动态共价键，研究发现：一、细菌感知材料表面萜类分子立体化学信号，不与材料表面粘附（实现了抗粘附），可用于新型抗菌纺织品保护皮肤自有菌群，阻止有害菌侵袭。二、基于席夫碱动态共价键，材料在感知细菌接触及繁殖信号的情况下，响应性释放萜类分子杀菌（实现了接触释放杀菌），可用于构建智能抗菌涂层，发展新型医疗器械。通过项目实施：一、揭示了该类智能高分子抗菌的构效关系。二、建立了抗菌材料智能利用新方法，无载体、不依赖外场、不主动释放。三、验证了立体化学抗菌机制不产生耐受性。四、完成了针对耐药细菌的抗菌性能评价。五、确定了表面立体化学对微生物基因组学的影响。六、发展了“越狱”、“登陆”、“跨栏”等可视化抗菌评价新方法。该项目的科学意义在于揭示了一种感知识别类智能高分子抗菌的构效关系，并阐述了立体化学抗菌策略的科学内涵，为抗菌理论的研究和相关生物医学应用提供了一种新思路。在项目支持下，负责人培养博士研究生5人，硕士研究生10人；发表SCI学术论文18篇，含TOP论文11篇，受邀在科学专著发表综述1篇；申请国家发明专利6项，获授权发明专利5项；相关成果转化1项，专利转让65万元；与企业共建3个研发中心，推进新概念抗菌高分子材料走向应用。项目负责人学术兼职全国卫生产业企业管理学会抗菌产业分会学术副秘书长、中关村抗菌产业联盟副理事长、抗菌团体标准委员会委员；组织筹办了2018第三届抗菌科学与技术论坛，得到学术界同行的高度评价，推动了抗菌研究领域的蓬勃发展。