Bacteriophobic Coatings for Inhibition of Pathogenic Biofilms

说明(申请人提供)：抑制病原生物被膜的抗菌涂料 本建议描述了用于抑制骨科植入物上细菌细胞定植和生物膜形成的功能涂层的制备、表征和评价。细菌感染是植入物失败的第二大常见原因。这种感染建立在钢板、棒、螺丝和销上，需要长期的抗生素治疗和/或通过多次冲洗/清创程序移除植入物以根除感染，然后植入新的装置。这种治疗与患者的高发病率、功能丧失和巨大的医疗费用有关。为了满足这一需求，提出了作为细菌细胞附着的物理屏障或作为破坏细菌膜的生物活性部分的驱菌涂层。设计、合成和评价了一种抑制细菌定植的原型涂层。建议进行详细、系统的调查，包括这项为期四年的提案的以下具体目标： 目的1.利用噬菌体展示技术筛选与钛结合的多肽，并测定其与钛结合的亲和力和选择性。目的2.合成并表征功能性多价抗菌涂料。目的3.研究钛表面有无抗菌涂层对生物膜体外和体外的抑制作用。目的4.活体观察围术期感染率的降低。 成功完成这项研究的结果将是：1)确定一种或多种抗菌涂层；2)了解这一策略在降低种植体感染率方面的优势和局限性；3)确定提高性能的潜在设计变化；4)展示一种可减少抗生素的使用以及由此带来的与治疗抗生素耐药病原体相关的临床挑战的新方法；5)为未来对多种种植金属具有特定物理性能或生物活性的抗菌涂层的设计和制造做出贡献。 公共卫生相关性目前对植入物相关感染的治疗包括延长抗生素治疗和/或更换受感染的植入物。这种治疗方法并不理想，需要采取创新的策略来防止医疗器械上的细菌定植。这项建议通过开发和评估防止植入物相关感染的新涂层来满足这一国家健康需求。

DESCRIPTION (provided by applicant): Bacteriophobic Coatings for Inhibition of Pathogenic Biofilms This proposal describes the preparation, characterization, and evaluation of functional coatings for the inhibition of bacterial cell colonization and biofilm formation on orthopaedic implants. Bacterial infections are the second most commonly attributed cause of implant failure. Such infections, which become established on plates, rods, screws and pins, necessitate prolonged antibiotic treatment and/or removal of the implant with multiple washout/debridement procedures to eradicate the infection, followed by implantation of a new device. This treatment is associated with high patient morbidity, loss of function, and significant health care costs. To address this need, bacteria repellant coatings are proposed that function as a physical barrier to bacterial cell attachment or as bioactive moieties to disrupt the bacterial membrane. A prototypical coating that inhibits bacteria colonization has been designed, synthesized, and evaluated. A detailed, systematic investigation is proposed that encompasses the following specific aims for this four-year proposal: Aim 1. Identify peptides that bind to titanium using phage display and measure the binding affinity and selectivity of these peptides to titanium. Aim 2. Synthesize and characterize functional multivalent bacteriophobic coatings. Aim 3. Characterize biofilm inhibition in vitro and ex vivo on titanium with and without the bacteriophobic coating. Aim 4. Demonstrate reduction of perioperative infection rates in vivo. The results of successful completion of this study will be: 1) identification of one or more bacteriophobic coatings; 2) understanding of the advantages and limitations of this strategy to reduce the rate of implant infection; 3) identification of potential design variations for improved performance; 4) demonstration of a new approach that may lessen the use of antibiotics and the resulting clinical challenges associate with treating antibiotic resistant pathogens; and 5) contributions to the design and engineering of future bacteriophobic coatings that possess specific physical properties or biological activities for a variety of implant metals. PUBLIC HEALTH RELEVANCE The current treatment for implant-associated infections includes prolonged antibiotic treatment and/or replacement of the infected implant. This treatment is less than ideal, and innovative strategies to prevent bacterial colonization on medical devices are needed. This proposal addresses this national health need through development and evaluation of new coatings that prevent implant associated infections.