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