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探索聚合物基纳米复合材料中的电活性微环境,以使细菌细胞对低剂量嵌入的银纳米粒子敏感。

Exploring electroactive microenvironments in polymer-based nanocomposites to sensitize bacterial cells to low-dose embedded silver nanoparticles.

机构信息

Centre of Physics, University of Minho, Braga 4710-057, Portugal; Centre of Biological Engineering, University of Minho, Campus de Gualtar, Braga 4710-057, Portugal.

Centre of Physics, University of Minho, Braga 4710-057, Portugal; Centre of Biological Engineering, University of Minho, Campus de Gualtar, Braga 4710-057, Portugal.

出版信息

Acta Biomater. 2022 Feb;139:237-248. doi: 10.1016/j.actbio.2021.07.067. Epub 2021 Aug 3.

DOI:10.1016/j.actbio.2021.07.067
PMID:34358697
Abstract

The search for alternative antimicrobial strategies capable of avoiding resistance mechanisms in bacteria are highly needed due to the alarming emergence of antimicrobial resistance. The application of physical stimuli as a mean of sensitizing bacteria for the action of antimicrobials on otherwise resistant bacteria or by allowing the action of low quantity of antimicrobials may be seen as a breakthrough for such purpose. This work proposes the development of antibacterial nanocomposites using the synergy between the electrically active microenvironments, created by a piezoelectric polymer (poly(vinylidene fluoride-co-trifluoroethylene) (PVDF-TrFE)), with green-synthesized silver nanoparticles (AgNPs). The electrical microenvironment is generated via mechanical stimulation of piezoelectric PVDF-TrFE/AgNPs films using a lab-made mechanical bioreactor. The generated material's electrical response further translates to bacterial cells, namely Escherichia coli and Staphylococcus epidermidis which in combination with AgNPs and the specific morphological features of the material induce important antibacterial and antibiofilm activity. Both porous and non-porous PVDF composites have shown antibacterial characteristics when stimulated at a mechanical frequency of 4 Hz being the effect boosted when AgNPs were incorporated in the nanocomposite, reducing in more than 80% the S. epidermidis bacterial growth in planktonic and biofilm form. The electroactive environments sensitize the bacteria allowing the action of a low dose of AgNPs (1.69% (w/w)). Importantly, the material did not compromise the viability of mammalian cells, thus being considered biocompatible. The piezoelectric stimulation of PVDF-based polymeric films may represent a breakthrough in the development of antibacterial coatings for devices used at hospital setting, taking advantage on the use of mechanical stimuli (pressure/touch) to exert antibacterial and antibiofilm activity. STATEMENT OF SIGNIFICANCE: The application of physical methods in alternative to the common chemical ones is seen as a breakthrough for avoiding the emergence of antimicrobial resistance. Antimicrobial strategies that take advantage on the capability of bacteria to sense physical stimuli such as mechanical and electrical cues are scarce. Electroactive nanocomposites comprised of poly(vinylidene fluoride-co-trifluoroethylene (PVDF-TrFE) and green-synthesized silver nanoparticles (AgNPs) were developed to obtain material able to inhibit the colonization of microorganisms. By applying a mechanical stimuli to the nanocomposite, which ultimately mimics movements such as walking or touching, an antimicrobial effect is obtained, resulting from the synergy between the electroactive microenvironments created on the surface of the material and the AgNPs. Such environments sensitize the bacteria to low doses of antimicrobials.

摘要

由于抗菌药物耐药性的惊人出现,人们非常需要寻找能够避免细菌产生耐药机制的替代抗菌策略。应用物理刺激作为一种手段,使细菌对原本耐药的抗菌药物敏感,或者允许低剂量的抗菌药物发挥作用,这可能被视为实现这一目标的突破。本工作提出了一种使用压电聚合物(聚(偏二氟乙烯-共-三氟乙烯)(PVDF-TrFE))的电活性微环境与绿色合成的银纳米粒子(AgNPs)之间的协同作用来制备抗菌纳米复合材料的方法。通过使用实验室制造的机械生物反应器对压电 PVDF-TrFE/AgNPs 薄膜进行机械刺激,产生电微环境。产生的材料的电响应进一步转化为细菌细胞,即大肠杆菌和表皮葡萄球菌,与 AgNPs 以及材料的特定形态特征相结合,诱导重要的抗菌和抗生物膜活性。当以 4 Hz 的机械频率刺激时,多孔和非多孔的 PVDF 复合材料均显示出抗菌特性,而当纳米复合材料中加入 AgNPs 时,效果会增强,使表皮葡萄球菌在浮游和生物膜形式中的生长减少 80%以上。电活性环境使细菌敏感,允许低剂量的 AgNPs(1.69%(w/w))发挥作用。重要的是,该材料不会影响哺乳动物细胞的活力,因此被认为是生物相容的。基于 PVDF 的聚合物薄膜的压电刺激可能代表着开发用于医院环境的抗菌涂层的突破,利用机械刺激(压力/触摸)发挥抗菌和抗生物膜活性。意义声明:将物理方法应用于替代常见的化学方法被视为避免抗菌药物耐药性出现的突破。利用细菌感知物理刺激(如机械和电信号)的能力的抗菌策略还很缺乏。由聚(偏二氟乙烯-共-三氟乙烯(PVDF-TrFE)和绿色合成的银纳米粒子(AgNPs)组成的电活性纳米复合材料被开发出来,以获得能够抑制微生物定殖的材料。通过对纳米复合材料施加机械刺激,最终模拟行走或触摸等动作,从而获得抗菌效果,这是材料表面上形成的电活性微环境与 AgNPs 之间的协同作用的结果。这种环境使细菌对低剂量的抗菌药物敏感。

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