Selenium Coated Dialysis Catheters for Reduced Biofilm Formation

用于减少生物膜形成的硒涂层透析导管

• 批准号: 7155346
• 负责人: ERIC J TOBIN
• 金额: $ 17.62万
• 依托单位: SPIRE CORPORATION
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-09-30 至 2007-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7155346
• 关键词: antibacterial agents; bacterial disease; biofilm; biomaterial compatibility; biomaterial evaluation; biomedical equipment development; catheterization; cell adhesion; clinical biomedical equipment; communicable disease control; covalent bond; growth inhibitors; hemodialysis; laboratory mouse; medical complication; selenium; surface coating; toxicology

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.

描述（由申请人提供）：项目总结/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，通常需要进行干预或拔除导管。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器械中心感染。硒是人类的基本饮食需求。选定的硒化合物具有催化作用，并通过与硫醇反应产生超氧自由基（O2）。这些超氧化物的高局部浓度导致细菌细胞溶解，并且可以特别有效地防止生物膜形成，因为超氧化物的作用机制不需要细胞具有代谢活性。硒将通过等离子体预处理表面活化工艺（用于外表面和内腔表面）和化学附着的独特组合共价附着在导管表面上。由于它是催化性的，共价连接的化合物将保留在表面上并永久活性，不像常规的洗脱涂层通常在30天内消失，并且可能引起有害的全身效应。由于超氧自由基只有非常短的扩散寿命，硒涂层将仅具有局部活性，不会对器械与邻近人体细胞的生物相容性产生不利影响。这项资助将检验共价连接的硒涂层可以减少透析导管表面生物膜形成的假设。在I期，将在体外细菌流动池模型中评价涂层的有效性。将检查几种表面浓度的硒，以确定最低所需量，并最终确定最佳水平。将进行基线生物相容性和毒理学试验。项目叙述：拟议的项目将开发硒涂层，以减少透析导管上的生物膜形成和以器械为中心的感染。该涂层将通过保护通路和减少由感染的导管引起的继发性并发症而为透析患者提供显著的益处。由于透析导管中感染问题的普遍存在，有效的治疗可能会显著影响使用导管作为其主要通路的透析患者的医疗保健提供成本。