Plasma-initiated Cross-linked Nanocoatings asAnti-infection Agents

项目总结 去年在美国，有190多万人与医疗器械相关的感染导致 造成约98,000人死亡。抗生素耐药生物被膜形成菌在医学上造成许多问题 并对公众健康造成不利影响。为了解决这个问题，聪明的不含抗生素，抗感染 专门为导管设计的交联型纳米涂层(SCLN)已经被开发出来。我们已经使用了 用于构建sCLN的Ar等离子体技术。这些智能纳米涂料由丙烯酸组成 与银纳米颗粒(AgNP)以逐层方式交联的聚合物刷子 浓度为2.46微克/平方厘米。这是通过使用等离子体引发的“嫁接自”方法来实现的， 用原位Ar等离子体辅助还原。这些生物兼容的抗感染纳米涂层可以感知和 有效和有针对性地针对细菌和生物膜。涉及sCLN的机制研究表明 由附着的细菌和生物膜触发的复杂活动，而不仅仅是持续的抗菌剂释放。 我们认为，我们的sCLN可能是预防医疗植入物污染的未来。初步 数据表明，sCLN在根除抗药性和形成生物膜的细菌方面是有效的，包括 生物材料上的耐甲氧西林金黄色葡萄球菌、表皮葡萄球菌和大肠杆菌 用来做导尿管。与加载了 抗菌剂，是它们(1)对抗生素耐药性细菌的广泛活性，(2)减少细菌的能力 粘附性，(3)罕见的细菌耐药性激发，(4)寿命，(5)特异性，(6)生物相容性，和(7) 稳定性。 提出了三个综合的具体目标来检验这一假设，即sCLN可以使用 等离子体技术，并在医学相关环境中有效地防止细菌生物膜。在……里面 具体目标1，将探索实验变量以构建稳定的sCLN，并提高对 生物膜的形成。在具体目标2中，将评估sCLN的抗感染效果与几种不同的 革兰氏阳性和革兰氏阴性细菌的体外生物被膜形成菌株 微流控培养条件，专门模拟导尿管的实际环境。对中国传统文化的探索 作用机制的重点是在复杂的生物系统中诱导细菌细胞裂解 采用不同的活力测定方法进行研究。在具体目标3中，前两个目标将通过评估得到加强 细菌共培养条件下sCLN对人组织细胞的体外安全性。这项研究旨在改进 根除与医疗和生物医学设备有关的感染的现有技术。这部作品 项目资金也将加强费尔利·狄金森大学的研究项目，提供 学生有机会将理论知识应用于实际的、现实世界的科学应用。

PROJECT SUMMARY Last year in the United States there were more than 1.9 million medical-device-associated infections resulting in approximately 98,000 deaths. Antibiotic-resistant biofilm-forming bacteria create many problems in medicine and have detrimental implications for public health. To tackle this problem, “smart” antibiotic-free, anti-infection cross-linked nanocoatings (sCLNs) designed specifically for catheters have been developed. We have used argon plasma technology for the construction of sCLNs. These smart nanocoatings consist of acrylic acid polymer brushes that are cross-linked to silver nanoparticles (AgNPs) in a layer-by-layer fashion with an AgNP concentration of 2.46 µg/cm2. This was achieved by using a plasma-initiated “grafting-from” approach, coupled with in situ argon plasma-assisted reduction. These biocompatible anti-infection nanocoatings can sense and target bacteria and biofilms effectively and specifically. Mechanistic studies involving sCLNs demonstrate complex activity, triggered by adherent bacteria and biofilms, rather than mere sustained antimicrobial release. We propose that our sCLNs may be the future for the prevention of medical implant contaminations. Preliminary data suggest that sCLNs are efficacious for eradicating antibiotic-resistant, biofilm-forming bacteria including methicillin-resistant Staphylococcus aureus, Staphylococcus epidermidis, and Escherichia coli on biomaterials used to make catheters. Several potential advantages of sCLNs, compared to traditional surfaces loaded with antibacterial agents, are their (1) broad activity against antibiotic-resistant bacteria, (2) ability to reduce bacterial adhesion, (3) rare provocation of bacterial resistance, (4) longevity, (5) specificity, (6) biocompatibility, and (7) stability. Three integrated specific aims are proposed to test the hypothesis that sCLNs can be constructed using plasma technology and are effective at preventing bacterial biofilms in a medically relevant environment. In Specific Aim 1, experimental variables will be explored to construct stable sCLNs with increased sensitivity to biofilm formation. In Specific Aim 2, the anti-infective efficacy of sCLNs will be evaluated against several different gram-positive and gram-negative biofilm-forming strains of bacteria in vitro, under both stationary and microfluidic cultivation conditions, specifically to model the actual environment of catheters. An exploration of the mechanism of action with a focus on the induction of bacterial cell lysis in complex biological systems will be studied by using various viability assays. In Specific Aim 3, the first two aims will be augmented by evaluating the in vitro safety of sCLNs for human tissue cells in bacterial co-culture. This research seeks to improve upon existing techniques for the eradication of infections associated with medical and biomedical devices. This work and program funding will also enhance the research program at Fairleigh Dickinson University by providing students with opportunities to apply theoretical knowledge to practical, real-world scientific applications.