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; 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 细菌在医疗设备上的积累使患者有严重的感染风险，可能会威胁生命。 根除建立的生物膜形成感染仍然很困难，部分原因是累积的细菌 在物理和代谢上与同一生物体的浮游细胞（浮动单细胞）不同。 尽管该领域做出了巨大的努力，但生物膜水平对治疗的反应和环境变化一直是 由于缺乏可直接直接的稳健，定量和准确的生物膜表征而阻碍 与医疗设备表面相关。此外，植入物相关的生物膜中的抗生素渗透是 通常由于生物膜的致密和复杂的基质而限制。该项目的总体目标是开发 完全可以产生有关生物膜粘合剂和变形性的定量信息的技术。我们的工作 假设是，生物膜的这两种机械性能的变化，即粘合性和可变形性 疾病进展的直接标记。可以定量表征的工具的开发 控制细菌粘合剂的生物膜和相应材料表面的机械性能 - 可能是 以特定于规范的方式 - 将对医疗设备兼容性产生重大影响。通过访问 CPRI翻译和计算核心，拟议的研究将首先开发薄膜附着力 评估生物膜的测量技术，以确定生物膜抗生素之间的关联 电阻和粘附强度（目标1）。与探索生物膜粘附作用的探索，我们将利用 我们独特的特征套件，其中包括一个罕见的共聚焦原子力显微镜平台来评估 生物膜可变形性与抗生素耐药性之间的关系（AIM 2）。最后，我们将评估纳米颗粒 流动性认为是生物膜限制的量度，并开发了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在逻辑上 设计医疗设备对耐热生物膜感染的起源的希望减少了。