The hemocompatibility of a nitric oxide generating polymer that catalyzes S-nitrosothiol decomposition in an extracorporeal circulation model
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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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A Cu0 NP embedded ECC circuit with SNAP infusion yielded considerably less thrombus (0.4 ± 0.2 pixel/cm2) after 4 h compared with a Cu0 NP circuit without SNAP infusion (3.2 ± 0.2 pixel/cm2) or a control circuit without Cu0 NP (4.9 ± 0.5 pixel/cm2).
“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]
Because endogenous RSNO levels are low (1-10 μmol/L for SNO-albumin), this approach requires a consistent supply of infused RSNOs to provide continuous catalytic NO generation at the flowing blood/polymer tubing interface.
“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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- 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 › Nitric Oxide and Endothelin Effects
- Physical Sciences › Engineering › Biomedical Engineering › 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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