基于蜻蜓翅膀的智能响应性抗菌表面构建及相关机制研究

Device-related nosocomial infections due to the bacterial adhesion on surfaces are mainly responsible for the failures of surgery. Antibioadhesion surfaces alone fail to inhibit the following bacterial proliferation because of its passive nature. In contrast, the conventional antimicrobial surfaces exhibit biocidal activity, mainly relying on the biocides, which may cause environmental concerns as well as trigger antibiotic resistance. By integrating nano-protrusions stemming from dragonfly wings and surface morphology corresponding to low antibacterial adhesion, a micro/nano-structured model with the optimized antimicrobial and antibacterial adhesion activities is designed. According to this model, the bionic micro/nano- structured surface with both antimicrobial and antibacterial adhesion activities will be developed by the combination of micro/nano-imprint and reactive ion etching (RIE) together, then the smart stimuli-responsive polymers will render the structured surface dead bacteria-repellent. The key innovations of this project are: (1) For the first time, it is proposed to construct a bionic micro/nano-structured surface with both dual antimicrobial/anti-bioadhesion property; (2) The antimicrobial activity is entirely due to physical biocidal property from the nano -protrusions, thus eliminating the possibility of developing antibiotic resistance; and (3) Repellency against dead cell, originated from the stimuli-responsive polymeric brushes, guarantees the long-lasting antimicrobial activity. This study will help establish a novel platform of designing effective antimicrobial/antibioadhesion surface to eventually eliminate nosocomial infections.

病原性细菌在医用器械表面的大量滋生是引发感染、导致手术失败的主要原因。单纯抗菌黏附表面无法长期有效地抑制细菌生长，而依赖于抗菌剂的杀菌表面易对周围环境产生危害，并引发细菌耐药性。本项目以蜻蜓翅膀微纳结构为基本杀菌模型，结合抗细菌粘附几何拓扑理论，对微纳结构参数进行生物耦合分析，获得兼具最优杀菌性和抗细菌黏附性的微纳结构模型，以此模型为指导，利用微纳模板复制和反应离子刻蚀相结合的手段构建杀菌抗粘附的仿生性微纳结构表面，并将智能响应性分子刷引入微纳结构，达到促死细菌脱附的目的。本项目创新为：（1）首次提出构建兼具杀菌和抗粘附性的仿生微纳拓扑结构表面的学术思想，（2）其杀菌性源于结构本身，避免产生细菌耐药性；（3）智能响应性分子刷赋予表面促死细菌脱附性能，保障长久有效的抗菌性。该研究将为制备高效、可长期使用且不引发细菌耐药性表面提供研究基础，为最终解决由医用器械引发的院内感染问题，提供新思路。

致病性细菌在材料表面粘附引发的医疗器械感染问题，给人类生命健康安全带来严峻挑战。传统抗菌剂严重依赖于生化机制杀死细菌，对周围环境造成严重污染，并极大地引发了细菌耐药性风险。本项目研究受蜻蜓翅膀微纳结构抗菌性能启发，拟利用纯物理作用抗菌策略，实现安全、高效、广谱和长效的抗菌性能，从而有效避免生化学抗菌剂过度使用所引起的多重细菌耐药性等诸多问题。研究、分析并获取蜻蜓翅膀独特的微纳结构参数，获得杀菌和抗细菌粘附微纳结构模型，利用微纳模板复制、等离子体溅射、微纳阵列自生长等技术，构建了杀菌抗粘附的仿生性微纳结构表面，并将智能响应性分子刷引入微纳结构，达到杀菌-促死细菌脱附的多重功能。.本项目取得了如下创新成果：.（1）阐明了微纳结构参数（柱状单元长径比、间隔密度、粗糙度等）变化对微纳结构杀菌性及抗细菌黏附性影响规律；实现了兼具最优杀菌性及抗菌黏附性的微纳拓扑结构设计及制造技术。.（ 2） 在微纳结构表面构建分别具有干湿响应性和刺激响应性分子刷，阐明了分子刷结构坍塌和伸展状态对结构杀菌性和促死细菌脱附性的变化规律；.（ 3） 阐明微纳结构和响应性分子刷构型变化对杀菌性-抗黏附及促死细菌脱附协同作用机制， 构建具有长效抗菌性能和不引发细菌耐药性的功能表面。与本项目相关的所获得一系列研究成果，相关工作发表在包括Acta Biomaterialia, ACS Applied Materials & Interfaces, Chemical Engineering Journal，Journal of Materials Chemistry A等高水平SCI期刊，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。