Electrochemically Modulated Nitric Oxide (NO) Releasing Biomedical Devices via Copper(II)-Tri(2-pyridylmethyl)amine Mediated Reduction of Nitrite
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A controllable and inexpensive electrochemical nitric oxide (NO) release system is demonstrated to improve hemocompatibility and reduce bacterial biofilm formation on biomedical devices. Nitric oxide is produced from the electrochemical reduction of nitrite using a copper(II)-tri(2-pyridylmethyl)amine (Cu(II)TPMA) complex as a mediator, and the temporal profile of NO release can be modulated readily by applying different cathodic potentials. Single lumen and dual lumen silicone rubber catheters are employed as initial model biomedical devices incorporating this novel NO release approach. The modified catheters can release a steady, physiologically-relevant flux of NO for more than 7 days. Both single and dual lumen catheters with continuous NO release exhibit greatly reduced thrombus formation on their surfaces after short-term 7-h intravascular placement in rabbit veins (p < 0.02, n = 6). Three day in vitro antimicrobial experiments, in which the catheters are “turned on” for only 3 h of NO release each day, exhibit more than a 100-fold decrease in the amount of surface attached live bacteria (n = 5). These results suggest that this electrochemical NO generation system could provide a robust and highly effective new approach to improving the thromboresistance and antimicrobial properties of intravascular catheters and potentially other biomedical devices.
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Nitrite can generate NO via electrochemical reduction at an electrode surface using Cu(I) from Cu0 oxidation or Cu(II)-ligand complexes mimicking nitrite reductase.
“Recently, it was demonstrated that nitrite can also be used to generate NO via electrochemical reduction at an electrode surface with either Cu(I) ion generated from oxidation of Cu0145,146 or via the use of Cu(II)-ligand complexes that mimic the active site of nitrite reductase (e.g., Cu(II)-tri(2-pyridylmethyl)amine, Cu(II)TPMA).147”
From Recent advances in thromboresistant and antimicrobial polymers for biomedical applications: just say yes to nitric oxide (NO) (2016) · cites this paper as [147]
This electrochemical approach has been used to develop multi-lumen catheters with one lumen dedicated to generating NO electrochemically to reduce thrombus and microbial biofilm formation on catheter surfaces.
“This approach has been utilized to develop a new generation of multi-lumen catheters in which one lumen is dedicated to generating NO electrochemically to reduce thrombus and microbial biofilm formation on the surface of the catheters.147,258”
From Recent advances in thromboresistant and antimicrobial polymers for biomedical applications: just say yes to nitric oxide (NO) (2016) · cites this paper as [147]
NO releasing or generating polymers can have strong bactericidal effects, even for bacteria able to metabolize and deactivate NO, such as P. aeruginosa with NO reductase.
“It has been clearly demonstrated that NO releasing/generating polymers can have strong bactericidal effects,19,146,147,162,201,227,283,284 even for bacteria that are able to metabolize and deactivate NO, such as P. aeruginosa, that possesses NO reductase enzyme that converts NO to nitrous oxide (N2O) and ultimately nitrogen (N2).86,201,219”
From Recent advances in thromboresistant and antimicrobial polymers for biomedical applications: just say yes to nitric oxide (NO) (2016) · cites this paper as [147]
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Wo, Y., Brisbois, E. J., Bartlett, R. H., & Meyerhoff, M. E. (2016) · Biomaterials Science · doi:10.1039/c6bm00271d · Cited by 251 · see citing works
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Self-citationColletta, A., Wu, J., Wo, Y., Kappler, M., Chen, H., Xi, C., & Meyerhoff, M. E. (2015) · ACS Biomaterials Science & Engineering · doi:10.1021/acsbiomaterials.5b00032 · Cited by 89 · see citing works
Self-citationThromboresistant/anti-biofilm catheters via electrochemically modulated nitric oxide release
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Self-citationRen, H., Coughlin, M. A., Major, T. C., Aiello, S., Rojas Pena, A., Bartlett, R. H., & Meyerhoff, M. E. (2015) · Analytical Chemistry · doi:10.1021/acs.analchem.5b01590 · Cited by 30 · see citing works
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- Authors
- Ren, H., Wu, J., Xi, C., Lehnert, N., Major, T., Bartlett, R. H., & Meyerhoff, M. E.
- Affiliations
- University of Michigan (US)
- Corresponding author
- Meyerhoff, Mark E.
- Venue
- ACS Applied Materials & Interfaces
- Publisher
- American Chemical Society (ACS)
- Published
- 2014-03-10
- Volume
- 6
- Issue
- 6
- Pages
- 3779-3783
- ISSN
- 1944-8244 (ISSN-L)
- 1944-8252
- PMC
- PMC3969097
- OpenAlex
- W2317490821
- Cited by
- 69
- References
- 26
- Citations by year
- 2026: 3 · 2025: 5 · 2024: 5 · 2023: 4 · 2022: 9 · 2021: 2 · 2020: 1 · 2019: 14 · 2018: 5 · 2017: 7 · 2016: 5 · 2015: 8 · 2014: 1
- FWCI
- 4.65
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Locations
- ACS Applied Materials & Interfaces (publishedVersion, other-oa)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- NIH Office of the Director (EB-000783)
- Topics
- Health Sciences › Medicine › Physiology › Nitric Oxide and Endothelin Effects
- Physical Sciences › Engineering › Electrical and Electronic Engineering › Electrochemical sensors and biosensors
- Physical Sciences › Materials Science › Surfaces, Coatings and Films › Polymer Surface Interaction Studies
- Keywords
- nitric oxide release, electrochemical mediator, intravascular catheters, hemocompatibility, thromboresistance, bacterial biofilm inhibition, antimicrobial surfaces, silicone rubber catheters, biomedical devices
- MeSH terms
- Animals, Bacteria, Copper, Humans, Nitric Oxide, Nitrites, Organometallic Compounds, Pyridines, Rabbits, Catheter-Related Infections, Vascular Access Devices
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