Bacteriophobic Coatings for Inhibition of Pathogenic Biofilms

项目摘要/摘要 抑制病原生物被膜的抗菌涂料 本建议书描述了功能涂料的制备、表征和评价。 抑制骨科植入物细菌细胞定植和生物膜形成。细菌感染是 第二个最常见的原因是种植失败。这种感染是建立在 板、棒、螺钉和销，需要长时间的抗生素治疗和/或取出植入物 进行多次冲洗/清创手术以根除感染，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。至 为了满足这一需要，提出了起到细菌细胞物理屏障作用的驱菌涂层 附着或生物活性部分，以破坏细菌膜。一种典型的涂层，可以抑制 细菌定植已经被设计、合成和评估。一项详细、系统的调查是 提议包括这项为期四年的提议的下列具体目标： 目的1.利用噬菌体展示技术鉴定与钛结合的多肽，并测定其与钛的结合亲和力 这些多肽对钛的选择性。 目的2.合成并表征功能性多价抗菌涂料。 目的3.具有和不具有抑菌剂的钛的体外和体外生物膜抑制特性 涂层。 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)鉴定出一个或多个恐菌者 涂层；2)了解这一策略的优点和局限性，以降低种植率 感染；3)确定改进性能的潜在设计变化；4)演示新的 一种可能减少抗生素的使用以及由此带来的与治疗相关的临床挑战的方法 抗药性病原体；以及5)对未来细菌恐惧症的设计和工程的贡献 对多种植入金属具有特定物理性能或生物活性的涂层。项目叙事 抑制病原生物被膜的抗菌涂料 目前对种植体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。这种治疗方法不够理想，并创新策略预防 医疗器械上的细菌定植是必要的。这项提案解决了这一国民健康需求。 通过开发和评估可防止植入物相关感染的新涂层。

PROJECT SUMMARY/ABSTRACT 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. PROJECT NARRATIVE Bacteriophobic Coatings for Inhibition of Pathogenic Biofilms 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.