Bacteriophobic Coatings for Inhibition of Pathogenic Biofilms

用于抑制致病生物膜的抗菌涂层

• 批准号: 7461115
• 负责人: MARK W. GRINSTAFF
• 金额: $ 41.59万
• 依托单位: BOSTON UNIVERSITY (CHARLES RIVER CAMPUS)
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-04-01 至 2012-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7461115
• 关键词: Address; Adsorption; Affect; Affinity; Aftercare; Amino Acids; Animals; Antibiotic Resistance; Antibiotic Therapy; Antibiotics; Appearance; Area; Bacteria; Bacterial Adhesion; Bacterial Infections; Binding; Biological; Biology; Biomedical Engineering; Biotin; C-reactive protein; Cartoons; Cell Adhesion; Cell membrane; Cell-Matrix Junction; Cells; Chemical Engineering; Chemistry; Classification; Clinic; Clinical; Condition; Count; Coupled; Coupling; Covalent Interaction; Debridement; Development; Devices; Engineering; Enzyme-Linked Immunosorbent Assay; Evaluation; Excision; Exhibits; External Fixation Devices; Failure; Fibronectins; Focus Groups; Fracture; Future; Glass; Goals; Gold; Growth; Hand; Health; Health Care Costs; Hip region structure; Histology; Hour; Image; Implant; In Vitro; Infection; Investigation; Ionic Strengths; Knee Prosthesis; Leg; Length; Libraries; Measures; Medical; Medical Device; Membrane; Metals; Microbial Biofilms; Modeling; Monitor; Morbidity - disease rate; Morphology; Operative Surgical Procedures; Orthopedics; Oryctolagus cuniculus; Outcome; Patients; Peptide Library; Peptide Synthesis; Peptides; Performance; Perioperative; Phage Display; Phase; Play; Polyethylene Glycols; Preparation; Procedures; Protein Inhibition; Proteins; Public Health; Quartz; Range; Rate; Research; Role; Scanning Electron Microscopy; Screening procedure; Serum; Silver; Simulate; Site; Solid; Solutions; Specificity; Stainless Steel; Standards of Weights and Measures; Staphylococcus aureus; Surface; Surgical complication; System; Technology; Temperature; Testing; TiAl6V4; Tibial Fractures; Time; Tissues; Titanium; Variant; White Blood Cell Count procedure; Whole Blood; Work; base; bone; clinically significant; compare effectiveness; design; engineering design; fluid flow; implant material; implantable device; implantation; improved; in vivo; inhibitor/antagonist; innovation; interdisciplinary approach; loss of function; magainin; medical implant; novel strategies; pathogen; physical property; prevent; protein aminoacid sequence; research study; retinal rods; success; surface coating; tibia

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.

描述（由申请人提供）：用于抑制致病生物膜的噬菌体涂层 该建议描述了功能涂层在骨科植入物上抑制细菌细胞定植和生物膜形成的功能涂层的制备，表征和评估。细菌感染是植入物衰竭的第二常见原因。这种感染已建立在板，杆，螺钉和销钉上，需要长时间使用抗生素治疗和/或通过多次洗涤/清理程序去除植入物，以消除感染，然后植入新设备。这种治疗与患者发病率高，功能丧失和大量医疗保健成本有关。为了满足这一需求，提出了细菌驱虫剂涂料，它是细菌细胞附着的物理障碍或破坏细菌膜的生物活性部分的物理障碍。已经设计，合成和评估了一种抑制细菌定植的典型涂层。提出了一项详细的系统调查，涵盖了以下四年提案的具体目的： 目的1。使用噬菌体显示并测量这些肽与钛的结合亲和力和选择性，鉴定与钛结合的肽。 AIM 2。合成并表征功能性多价噬菌体涂层。 AIM 3。表征体外生物膜抑制作用，并在有或没有噬菌体涂层的情况下在钛上的体内抑制。 AIM 4。证明体内围手术期感染率降低。 这项研究成功完成的结果将是：1）鉴定一种或多种噬菌体涂层； 2）理解降低植入物感染率的策略的优势和局限性； 3）识别潜在的设计变化以提高性能； 4）展示一种新方法，可以减少抗生素的使用以及与治疗抗生素耐药病原体有关的临床挑战； 5）对具有特定物理特性或各种植入物金属的生物活性的未来噬菌体涂层的设计和工程贡献。 公共卫生相关性当前对植入物相关感染的治疗包括长时间的抗生素治疗和/或替代感染植入物。这种治疗方法并不理想，需要在医疗设备上预防细菌定植的创新策略。该提案通过开发和评估预防植入物相关感染的新涂料来解决这种国家健康的需求。