Research Project
7155346
[unreadable] 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. [unreadable] [unreadable] [unreadable]
