Bacteriophobic Coatings for Inhibition of Pathogenic Biofilms

描述（由申请人提供）：用于抑制病原性生物膜的疏菌涂层 本提案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效的第二大常见原因。此类感染在接骨板、棒、螺钉和骨针上形成，需要长期抗生素治疗和/或通过多次冲洗/清创手术移除植入物以根除感染，然后植入新器械。这种治疗与高患者发病率、功能丧失和显著的医疗保健成本相关。为了解决这一需求，提出了细菌排斥涂层，其用作细菌细胞附着的物理屏障或用作生物活性部分以破坏细菌膜。一个原型的涂层，抑制细菌定植的设计，合成和评估。建议进行详细、系统的调查，其中包括这一四年期提案的以下具体目标： 目标1.使用噬菌体展示鉴定与钛结合的肽，并测量这些肽对钛的结合亲和力和选择性。目标2.合成和表征功能性多价疏菌涂料。目标3：在体外和离体条件下，表征具有和不具有疏菌涂层的钛上的生物膜抑制。目标4。证明体内围手术期感染率降低。 成功完成本研究的结果将是：1）识别一种或多种疏菌涂层; 2）了解该策略在降低植入物感染率方面的优势和局限性; 3）识别潜在设计变更以改善性能; 4）展示一种新的方法，可以减少抗生素的使用，以及由此产生的与治疗抗生素耐药病原体相关的临床挑战;和5）对未来具有用于各种植入金属的特定物理性质或生物活性的疏菌涂层的设计和工程的贡献。 公共卫生相关性目前植入物相关感染的治疗包括长期抗生素治疗和/或更换受感染的植入物。这种治疗方法并不理想，需要创新策略来防止医疗器械上的细菌定植。该提案通过开发和评价预防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.