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The hemocompatibility of a nitric oxide generating polymer that catalyzes S-nitrosothiol decomposition in an extracorporeal circulation model
Open accessAbstract
Nitric oxide (NO) generating (NOGen) materials have been shown previously to create localized increases in NO concentration by the catalytic decomposition of blood S-nitrosothiols (RSNO) via copper (Cu)-containing polymer coatings and may improve extracorporeal circulation (ECC) hemocompatibility. In this work, a NOGen polymeric coating composed of a Cu⁰-nanoparticle (80 nm)-containing hydrophilic polyurethane (SP-60D-60) combined with the intravenous infusion of an RSNO, S- nitroso-N-acetylpenicillamine (SNAP), is evaluated in a 4 h rabbit thrombogenicity model and the anti-thrombotic mechanism is investigated. Polymer films containing 10 wt.% Cu⁰-nanoparticles coated on the inner walls of ECC circuits are employed concomitantly with systemic SNAP administration (0.1182 μmol/kg/min) to yield significantly reduced ECC thrombus formation compared to polymer control + systemic SNAP or 10 wt.% Cu NOGen + systemic saline after 4 h blood exposure (0.4 ± 0.2 NOGen/SNAP vs 4.9 ± 0.5 control/SNAP or 3.2 ± 0.2 pixels/cm² NOGen/saline). Platelet count (3.9 ± 0.7 NOGen/SNAP vs 1.8 ± 0.1 control/SNAP or 3.0 ± 0.2 × 10⁸/ml NOGen/saline) and plasma fibrinogen levels were preserved after 4 h blood exposure with the NOGen/SNAP combination vs either the control/SNAP or the NOGen/saline groups. Platelet function as measured by aggregometry (51 ± 9 NOGen/SNAP vs 49 ± 3% NOGen/saline) significantly decreased in both the NOGen/SNAP and NOGen/saline groups while platelet P-selectin mean fluorescence intensity (MFI) as measured by flow cytometry was not decreased after 4 h on ECC to ex vivo collagen stimulation (26 ± 2 NOGen/SNAP vs 29 ± 1 MFI baseline). Western blotting showed that fibrinogen activation as assessed by Aγ dimer expression was reduced after 4 h on ECC with NOGen/SNAP (68 ± 7 vs 83 ± 3% control/SNAP). These results suggest that the NOGen polymer coating combined with SNAP infusion preserves platelets in blood exposure to ECCs by attenuating activated fibrinogen and preventing platelet aggregation. These NO-mediated platelet changes were shown to improve thromboresistance of the NOGen polymer-coated ECCs when adequate levels of RSNOs are present.
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“The Cu0 NP embedded ECC circuit with SNAP infusion yields considerably less thrombus (0.4 ± 0.2 pixel/cm2) on the surface of the chamber after 4 h, as compared to the Cu0 NP circuit without SNAP infusion (3.2 ± 0.2 pixel/cm2) or the control circuit without Cu0 NP (4.9 ± 0.5 pixel/cm2).”
From Recent advances in thromboresistant and antimicrobial polymers for biomedical applications: just say yes to nitric oxide (NO) (2016) · cites this paper as [254]
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“Of note, since the endogenous RSNO levels are low (e.g., 1–10 µmol/L for SNO-albumin),280 this approach requires consistent supply of infused RSNOs to provide continuous catalytic generation of NO at the flowing blood/polymer tubing interface.254”
From Recent advances in thromboresistant and antimicrobial polymers for biomedical applications: just say yes to nitric oxide (NO) (2016) · cites this paper as [254]
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Metadata
- Authors
- Major, T. C., Brant, D. O., Burney, C. P., Amoako, K. A., Annich, G. M., Meyerhoff, M. E., Handa, H., & Bartlett, R. H.
- Affiliations
- University of Michigan (US)
- Corresponding author
- Major, Terry C.
- ORCID
- Venue
- Biomaterials
- Publisher
- Elsevier BV
- Published
- 2011-09
- Volume
- 32
- Issue
- 26
- Pages
- 5957-5969
- ISSN
- 0142-9612 (ISSN-L)
- PMC
- PMC3153416
- OpenAlex
- W1977237239
- Cited by
- 118
- References
- 47
- Citations by year
- 2026: 6 · 2025: 5 · 2024: 6 · 2023: 9 · 2022: 14 · 2021: 5 · 2020: 6 · 2019: 11 · 2018: 8 · 2017: 10 · 2016: 7 · 2015: 10 · 2014: 8 · 2013: 9 · 2012: 2
- FWCI
- 3.10
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- Locations
- Biomaterials (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Digital Commons - New Heaven (University of New Haven) (submittedVersion, cc-by-nc-nd)
- Funders
- National Institutes of Health (R01 HD 01534, EB-004527)
- Topics
- Physical Sciences › Materials Science › Surfaces, Coatings and Films › Polymer Surface Interaction Studies
- Health Sciences › Medicine › Physiology (medical) › Nitric Oxide and Endothelin Effects
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Mechanical Circulatory Support Devices
- Keywords
- copper nanoparticles, polyurethane coatings, extracorporeal circulation, hemocompatibility, thrombogenicity, S-nitroso-N-acetylpenicillamine, platelet aggregation, fibrinogen activation, P-selectin
- MeSH terms
- Animals, Extracorporeal Circulation, Fibrinogen, Flow Cytometry, Fluorescent Antibody Technique, Humans, Nitric Oxide, Polymers, Rabbits, Blotting, Western, S-Nitrosothiols
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