Plasma-initiated Cross-linked Nanocoatings asAnti-infection Agents

等离子体引发的交联纳米涂层作为抗感染剂

• 批准号: 10717476
• 负责人: Christian Traba
• 金额: $ 25.72万
• 依托单位: FAIRLEIGH DICKINSON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-07-10 至 2028-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10717476
• 关键词: American; Anti-Bacterial Agents; Anti-Infective Agents; Antibiotic Resistance; Antibiotics; Argon; Bacteria; Bacterial Adhesion; Bacterial Antibiotic Resistance; Bacterial Drug Resistance; Binding; Biocompatible Materials; Biological; Biological Assay; Catheters; Cell Line; Cell membrane; Cells; Cessation of life; Charge; Clinical; Coculture Techniques; Collaborations; Complex; Copper; Coupled; Cross Infection; Cytolysis; Data; Devices; Dryness; Engineering; Environment; Enzymes; Erythrocytes; Escherichia coli; Excretory function; Exposure to; Extravasation; Funding; Future; Grant; Health Personnel; Hospitals; Human; Immobilization; Impairment; In Situ; In Vitro; Infection; Infection prevention; Iron; Knowledge; Lead; Length; Leukocytes; Longevity; Medical; Medical Care Costs; Medical Device; Medicine; Methicillin Resistance; Microbial Biofilms; Microfluidics; Modeling; Modern Medicine; Modification; Monitor; Patients; Persons; Plasma; Polymers; Prevention; Process; Prosthesis; Proteins; Protocols documentation; Public Health; Quality of life; Recurrence; Research; STEM student; Safety; Silver; Specificity; Stains; Staphylococcus aureus; Staphylococcus epidermidis; Students; Surface; System; Techniques; Technology; Testing; Toxic effect; United States; Universities; Visit; Work; acrylic acid; antimicrobial; bacterial resistance; biomaterial compatibility; combat; complex biological systems; cost; crosslink; density; design; human tissue; implantable device; improved; in vivo; innovation; macromolecule; medical implant; methicillin resistant Staphylococcus aureus; microorganism; monomer; nanocoating; nanoparticle; operation; prevent; programs; sugar; surface coating

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.

项目摘要 去年在美国有超过190万例医疗器械相关感染， 造成了大约98,000人死亡耐抗生素的生物膜形成细菌在医学上产生了许多问题 并对公众健康产生有害影响。为解决这一问题，“智能”免杀虫剂、抗感染 已经开发了专门为导管设计的交联纳米涂层（sCLN）。我们已经使用 氩等离子体技术用于构建sCLN。这些智能纳米涂料由丙烯酸 聚合物刷以逐层方式与银纳米颗粒（AgNP）交联， 浓度为2.46 µg/cm 2。这是通过使用等离子体引发的“嫁接”方法， 用原位氩等离子体辅助还原。这些生物相容性抗感染纳米涂层可以感知和 有效和特异地靶向细菌和生物膜。涉及sCLN的机制研究表明， 这是一种复杂的活性，由粘附的细菌和生物膜触发，而不仅仅是持续的抗菌剂释放。 我们建议，我们的sCLN可能是未来的医疗植入物污染的预防。初步 数据表明，sCLN可有效根除耐药性生物膜形成细菌， 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 用来做导管与传统的表面相比，sCLN的几个潜在优势是负载有 抗菌剂的特征是它们（1）对耐药性细菌的广泛活性，（2）减少细菌感染的能力， 粘附性，（3）细菌耐药性的罕见激发，（4）寿命，（5）特异性，（6）生物相容性，和（7） 稳定 提出了三个综合的具体目标，以检验sCLN可以使用 等离子体技术，并有效地防止医学相关环境中的细菌生物膜。在 具体目标1，将探索实验变量以构建稳定的sCLN， 生物膜形成在具体目标2中，将针对几种不同的抗感染药物评价sCLN的抗感染疗效。 革兰氏阳性和革兰氏阴性细菌生物膜形成菌株在体外，在静止和 微流体培养条件，特别是模拟导管的实际环境。的探索 作用机制，重点是在复杂的生物系统中诱导细菌细胞裂解， 通过使用各种可行性分析进行研究。在具体目标3中，前两个目标将通过评估 sCLN在细菌共培养中对人体组织细胞的体外安全性。这项研究旨在改善 用于根除与医疗和生物医学装置相关的感染的现有技术。这项工作 和计划资金也将加强在费尔利迪金森大学的研究计划， 学生有机会将理论知识应用于实际，现实世界的科学应用。