抗细菌粘附与杀菌双功能层状高分子刷体系的构建与性能

Nosocomial infections, which are induced by the bacteria adhered on the surface of biomedical devices, are seriously threatening to the health of patients. At present, it's an ideal strategy to obtain the excellent antibacterial properties via the synergy of anti-bacterial adhesion and bactericidal properties. However, the surface grafting both anti-bacterial adhesion chain (segment) and bactericidal chain (segment), resulting in not only the decrease of their graft densities, but the mutual interference of their performances. The desired antimicrobial properties are hardly to be obtained. Aiming at the above common problems, a novel preparation strategy of the antimicrobial surface is proposed in this project. That is, a high-density anti-bacterial adhesion bottom brush firstly graft from the polymer surface via living graft polymerization, followed by grafting bactericidal upper brush. The main topics as follows will be investigated. ① Design and synthesis of the bactericidal monomer with special properties; ② Preparation of the anti-bacterial adhesion and bactericidal two-layer brush; ③ The antibacterial properties and biocompatibility of the two-layer brush. The key innovations are: the academic idea of constructing the anti-bacterial adhesion and bactericidal two-layer brush is first proposed. The problems of the decrease of their graft densities will be solved, and the mutual interference of their antibacterial performances will be avoided. A much more excellent long-lasting antibacterial performance will be obtained. This study will provide a new idea for ultimately solving the problem of nosocomial infections caused by the biomedical devices.

医疗器械在存储或介（植）入体内后，其表面滋生细菌引发的院内感染严重威胁着患者的健康。目前，协同抗细菌粘附与杀菌性能是获得优良抗菌性能的理想策略。然而，表面共接枝抗粘链（段）和杀菌链（段），不仅各自接枝密度均会降低，同时性能相互影响，难以获得理想的效果。针对上述共性矛盾，本项目提出了新的抗菌表面构建策略：采用活性接枝聚合方法，在聚合物表面构筑高密度的抗粘底层刷，然后在底层刷上再接枝杀菌刷。主要研究：①特殊结构杀菌单体的设计与合成；②具有抗粘附与杀菌双层高分子刷的制备；③双层功能刷的抗菌性能与生物相容性。创新为：提出高分子表面构建抗细菌粘附和杀菌双层分子刷的学术思想，解决各自接枝链密度降低的问题，并且避免性能相互干扰，长效抗菌性能预期更优异。该研究将为最终解决由医疗器械引发的院内感染问题，提供新思路。

医疗器械在存储或介/植入体内后，其表面细菌滋生是引发院内感染的主因。协同抗细菌粘附与杀菌性能是获得优良抗菌性能的理想策略。然而，表面共接枝抗粘附和杀菌链段存在各自接枝密度降低以及性能相互影响的问题。为此，本项目提出采用活性接枝聚合方法，构建抗细菌粘附和杀菌双层高分子刷的学术思想。 .主要研究内容：①特殊结构杀菌单体的设计与合成；②具有抗粘附与杀菌双层高分子刷的制备；③双层功能刷的抗菌性能与生物相容性。.重要结果、关键数据等及其科学意义或应用前景.①抗粘附与杀菌双层高分子刷表面制备以及抗菌与生物相容性评价.通过构建底层PEGMA抗污，上层PDMAEMA杀菌的双层结构表面，证实抗污底层可以抑制大多数细菌粘附，杀菌上层可以杀死少量粘附细菌；由于抗粘附和杀菌刷处于不同空间位置，可以显著降低功能间的干扰；另外，抗粘附底层降低了对杀菌层密度的要求，赋予表面良好的生物相容性。.②针对器械在实际使用中存在的抗感染和生物相容性能的阶段性需求以及性能互相矛盾的难题，提出了生物适配性层状高分子刷表面构建思想，先后获得了湿度响应、温度响应和细菌响应的医用表面体系。. 构建的湿度响应表面具有抗粘附层在上，杀菌层在下的结构特点，通过上下层的相互配合，实现了干态杀菌和湿态抗粘附功能的可逆转化。由于抗菌功能仅由水化作用驱动，摆脱了传统化学转化的局限，操作简便。构建的温敏型上层杀菌-下层抗粘附转化表面具有常温下杀菌，体温下抗细菌粘附的功能，与临床实际需求的匹配性较好。构建的非释放型细菌响应性抗菌表面，主要利用pH诱导响应性外层对抗菌肽内层的可逆性暴露与掩盖机制，巧妙实现了非释放型杀菌及死细菌清除的往复循环，提供了智能抗菌的新模式和抗菌肽使用的新思路。.本项目工作将为解决由医疗器械引发的院内感染问题，提供新思路。相关研究工作先后被ACS Applied Materials & Interfaces (2017, 9: 37611)，Advanced Healthcare Material (2019, 1801381), Journal of Materials Chemistry B (2018, 6: 4274)，Macromolecular Rapid Communications (2018, 39: 1800189)等期刊给予大段评述和原图引用。