# Advanced Thromboresistant/Bactericidal Catheters via Electromodulated NO Release

> **NIH NIH R01** · UNIVERSITY OF MICHIGAN AT ANN ARBOR · 2020 · $294,045

## Abstract

Abstract:
!
Nitric oxide (NO) secretion by the normal endothelium inhibits clotting by preventing platelet activation and
adhesion. Nitric oxide is also a potent antimicrobial agent and is capable of preventing/dispersing biofilms.
Over the past decade, several groups, including ours, have developed novel materials that continuously
secrete NO from various NO donors embedded within polymers to prevent platelet adhesion, thrombosis
and microbial biofilm formation on the surface of a number of biomedical devices (e.g., intravascular
catheters/sensors, extracorporeal circulation loops, etc.) and wound healing bandages. However, to date,
there have not yet been any commercial applications of this technology owing to the high cost of preparing
and shipping commodity devices made with the fragile NO donors species, which are often sensitive to
moisture and increased temperature. To overcome this hurdle, we now propose a completely new, low cost
and robust alternate method to create a new generation of thromboresistant/bactericidal intravascular and
urinary catheters, as well as other biomedical devices. This approach is based on the use of
electrochemically modulated NO release from an inner reservoir of a simple inorganic nitrite salt. The most
promising approach toward this goal is to utilize soluble Cu(II)-ligand complexes that mimic the active
Cu(II/I) site of nitrite reductase enzymes. These complexes can be electrochemically reduced to Cu(I)
species that further mediate the one electron reduction of nitrite to NO. Substantive preliminary data are
already in hand (based on a R-56 bridge award) demonstrating the ability of such electrochemical NO
release catheters to prevent and/or disperse microbial biofilm formation in vitro and also substantially
decrease thrombus formation in vivo. Further optimization of the electrochemistry, especially identifying
new Cu(II)-ligand complexes that have high efficiency in mediating the reduction of nitrite to NO, and
modeling/testing the NO release profiles of this approach in a dual-lumen catheter configuration is needed
to enable extensive in vitro and in vivo studies. In vitro testing will focus on examining the antimicrobial
activity of the basic technology, especially with respect to activity against microbes commonly associated
with intravascular and urinary catheter induced clinical infections. Additionally, the proposed research will
include studies of the new electrochemical NO release catheters within the veins/arteries sheep (14 d) with
the goal of evaluating the efficacy of these devices in preventing thrombosis and microbial biofilm formation
in vivo. An in vivo comparison study of the intravascular antimicrobial activity of the new electrochemical
NO release catheters vs. commercial antibiotic impregnated catheters will also be conducted. A
miniaturized battery powered circuitry will be developed to aid in the 14 d studies in fully awake sheep.
Success of this project could lead to a new generatio...

## Key facts

- **NIH application ID:** 9847987
- **Project number:** 5R01HL132037-04
- **Recipient organization:** UNIVERSITY OF MICHIGAN AT ANN ARBOR
- **Principal Investigator:** MARK E MEYERHOFF
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $294,045
- **Award type:** 5
- **Project period:** 2017-01-01 → 2021-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9847987

## Citation

> US National Institutes of Health, RePORTER application 9847987, Advanced Thromboresistant/Bactericidal Catheters via Electromodulated NO Release (5R01HL132037-04). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9847987. Licensed CC0.

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