Quantitative mechanical phenotyping of bacterial biofilms on implant surfaces

项目总结/摘要-项目2 医疗器械上的细菌积累使患者面临严重的感染风险，并可能危及生命。 根除已建立的生物膜形成感染仍然很困难，部分原因是积累的细菌 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。 尽管在该领域中进行了大量的努力，但生物膜水平对处理和环境变化的响应已经被证明是不可靠的。 由于缺乏可靠的、定量的和准确的生物膜表征技术， 与医疗器械表面相关。此外，抗生素在植入物相关生物膜中的渗透， 通常由于生物膜的致密和复杂基质而受到限制。该项目的总体目标是开发 补充技术，产生关于生物膜粘附性和可变形性的定量信息。我们的工作 假设这两种机械性能的变化，即，生物膜的粘附性和可变形性是一种 疾病进展的直接标志物。开发能够定量描述 生物膜和相应的控制细菌粘附的材料表面的机械性能-可能 将对医疗器械兼容性产生重大影响。借助访问 CPRI的翻译和计算核心，拟议的研究将首先开发一个膜粘附 用于评估生物膜以确定生物膜抗生素 电阻和粘附强度（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，包括一个罕见的共焦原子力显微镜平台， 生物膜变形性和抗生素耐药性之间的关系（AIM 2）。最后，我们将评估纳米颗粒 流动性测定作为生物膜限制的测量，并开发关于药物载体的计算模型 扩散（AIM 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从逻辑上 设计具有降低的耐治疗性生物膜感染发生倾向的医疗器械。

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.