Quantitative mechanical phenotyping of bacterial biofilms on implant surfaces

种植体表面细菌生物膜的定量机械表型

• 批准号: 10112948
• 负责人: Martha Grady
• 金额: $ 26.6万
• 依托单位: UNIVERSITY OF KENTUCKY
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-03-01 至 2025-01-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10112948
• 关键词: 3-Dimensional; Adhesions; Adhesives; Amputation; Anti-Bacterial Agents; Antibiotic Resistance; Antibiotic Therapy; Antibiotics; Arthrodesis; Atomic Force Microscopy; Bacteria; Bacterial Adhesion; Biological Assay; Biology; Cells; Centers of Research Excellence; Cessation of life; Chemicals; Chemistry; Complex; Computer Models; Cues; Data; Development; Devices; Diffuse; Diffusion; Disease; Disease Marker; Disease Progression; Drug Carriers; Endocarditis; Enterococcus faecalis; Environment; Evaluation; Failure; Film; Goals; Image; Implant; Infection; Inflammation; Label; Lasers; Lead; Life; Literature; Malignant Neoplasms; Mammalian Cell; Measurement; Measures; Mechanics; Medical Device; Medical Device Designs; Medical Device Safety; Metabolic; Methods; Microbial Biofilms; Modeling; Nosocomial Infections; Organism; Outcome; Patients; Penetration; Pharmacologic Substance; Phenotype; Physiological; Polymers; Property; Quantum Dots; Research; Resistance; Role; Spectrum Analysis; Structure; Surface; System; Teacher Professional Development; Techniques; Therapeutic; Thinness; biomaterial compatibility; expectation; extracellular; implant associated infection; implantable device; improved; indexing; infection risk; innovation; interdisciplinary collaboration; mechanical properties; microorganism interaction; nanoparticle; novel; particle; screening; stem; tool; tool development; treatment response; veterinary science

PROJECT SUMMARY/ABSTRACT – PROJECT 2 Bacteria accumulation on medical devices puts a patient at serious risk for infection and could be life threatening. Eradication of established biofilm-forming infections remains difficult, in part because the accumulated bacteria are physiologically and metabolically distinct from the planktonic cells (floating single cells) of the same organism. Despite intense efforts in the field, biofilm level response to treatments and changes in environment has been hindered by the lack of robust, quantitative, and accurate biofilm characterization techniques that can be directly correlated to medical device surfaces. Furthermore, antibiotic penetration in implant-associated biofilms, is typically limited due to the dense and complex matrix of biofilms. The overall goal of this project is to develop complementary techniques that yield quantitative information on biofilm adhesion and deformability. Our working hypothesis is that changes in these two mechanical properties, i.e., adhesion and deformability, of biofilms is a direct marker of disease progression. The development of tools that can quantitatively characterize the mechanical properties of biofilms and corresponding material surfaces that control bacterial adhesion—possibly in a species-specific manner—will have a significant impact on medical device compatibility. Aided by access to the CPRI Translational and Computational Cores, the proposed research will first develop a film adhesion measurement technique for evaluation of biofilms to determine the association between biofilm antibiotic resistance and adhesion strength (AIM 1). Parallel to exploration of the role of biofilm adhesion, we will leverage our unique characterization suite that includes a rare confocal-atomic force microscopy platform to evaluate the relationship between biofilm deformability and antibiotic resistance (AIM 2). Lastly, we will evaluate nanoparticle mobility assays as a measure of biofilm confinement and develop computational models regarding drug carrier diffusion (AIM 3). Our expectation is that the results and tools developed here will guide us and others to logically design medical devices with a decreased propensity for the genesis of therapeutic-resistant biofilm infections.

项目摘要/摘要 – 项目 2 医疗设备上的细菌积累会使患者面临严重的感染风险，并可能危及生命。 根除已形成的生物膜感染仍然很困难，部分原因是累积的细菌 在生理和代谢上与同一生物体的浮游细胞（漂浮的单细胞）不同。 尽管在该领域付出了巨大的努力，生物膜水平对治疗和环境变化的反应仍然存在 由于缺乏稳健、定量和准确的生物膜表征技术而受到阻碍，这些技术可以直接 与医疗器械表面相关。此外，抗生素渗透到植入物相关的生物膜中， 由于生物膜基质致密且复杂，通常受到限制。该项目的总体目标是开发 产生生物膜粘附和变形性定量信息的补充技术。我们的工作 假设是生物膜这两种机械特性（即粘附性和变形性）的变化是 疾病进展的直接标志。开发能够定量表征的工具 控制细菌粘附的生物膜和相应材料表面的机械特性——可能 以特定物种的方式——将对医疗设备的兼容性产生重大影响。协助访问 CPRI 转化和计算核心，拟议的研究将首先开发薄膜粘附 用于评估生物膜以确定生物膜抗生素之间的关联的测量技术 电阻和粘合强度（AIM 1）。在探索生物膜粘附作用的同时，我们将利用 我们独特的表征套件，包括罕见的共焦原子力显微镜平台，用于评估 生物膜变形性与抗生素耐药性之间的关系（AIM 2）。最后，我们将评估纳米粒子 迁移率测定作为生物膜限制的衡量标准并开发有关药物载体的计算模型 扩散（目标 3）。我们的期望是，这里开发的结果和工具将指导我们和其他人逻辑地 设计医疗设备，降低产生耐药性生物膜感染的可能性。