Selenium Coated Dialysis Catheters for Reduced Biofilm Formation

项目简介/摘要：感染是影响透析导管功能和寿命的主要问题。导管相关性脓毒症的发生率高得惊人，通常需要干预或拔除导管。我们建议开发用于透析导管的硒基涂层，以防止细菌附着和定植，最终导致生物膜形成和装置中心感染。硒是人类必需的食物。选定的硒化合物具有催化作用，通过与硫醇反应产生超氧自由基（O2）。这些局部高浓度的超氧化物会导致细菌细胞的裂解，并可能特别有效地防止生物膜的形成，因为超氧化物的作用机制不需要细胞代谢活跃。硒将共价附着在导管表面，利用等离子体预处理表面活化过程（用于外表面和管腔表面）的独特组合，然后进行化学附着。由于它具有催化作用，因此共价附着的化合物将留在表面并永久保持活性，而传统的洗脱涂层通常在30天内就会消失，并可能引起有害的全身影响。由于超氧自由基的扩散寿命很短，因此硒涂层仅具有局部活性，不会对装置与邻近人体细胞的生物相容性产生不利影响。这项资助将研究共价附着的硒涂层可以减少透析导管表面生物膜形成的假设。在第一阶段，将在体外细菌流细胞模型中评估涂层的功效。将检查几种硒的表面浓度，以确定所需的最低量和最终的最佳水平。将进行基线生物相容性和毒理学试验。项目描述：该项目将开发硒涂层，以减少透析导管上的生物膜形成和设备中心感染。该涂层将通过保留通道和减少感染导管引起的继发性并发症，为透析患者提供显著的益处。由于透析导管感染问题的普遍存在，有效的治疗可能会显著影响透析患者使用导管作为主要途径的医疗保健服务成本。

DESCRIPTION (provided by applicant): Project Summary/Abstract: Infection is a major problem affecting function and longevity of dialysis catheters. Catheter-related sepsis occurs at alarmingly high rates, and often necessitates intervention or catheter removal. We propose to develop selenium-based coatings for dialysis catheters to prevent bacterial attachment and colonization that can ultimately lead to biofilm formation and device-centered infection. Selenium is an essential dietary requirement for humans. Selected selenium compounds are catalytic and produce superoxide radicals (O2) by their reaction with thiols. High local concentrations of these superoxides-cause lysis of bacterial cells, and could be particularly effective in preventing biofilm formation, since the mechanism of action for the superoxide does not require cells to be metabolically active. Selenium will be covalently attached to the surface of the catheters utilizing a unique combination of a plasma pre-treatment surface activation process (for both external and lumenal surfaces) followed by chemical attachment. Since it is catalytic, the covalently attached compound will remain on the surface and be active permanently, unlike conventional eluting coatings that are often gone within 30 days and that can elicit deleterious systemic effects. Since the superoxide radical has only a very short diffusion lifetime, the selenium coatings will be only locally active and will not adversely affect biocompatibility of the device with neighboring human cells. This grant will examine the hypothesis that a covalently attached selenium coating can reduce biofilm formation on the surface of dialysis catheters. In Phase I, efficacy of the coating will be evaluated in an in vitro bacterial flow cell model. Several surface concentrations of selenium will be examined to determine minimum required quantities and, ultimately, optimal levels. Baseline biocompatibility and toxicology tests will be conducted. Project Narrative: The proposed project would develop selenium coatings to reduce biofilm formation and device-centered infection on dialysis catheters. The coating would provide significant benefits to dialysis patients by preserving access and reducing secondary complications resulting from infected catheters. Due to the prevalence of the infection problem in dialysis catheters, an effective treatment could significantly impact cost of healthcare delivery for dialysis patients using catheters as their primary access.