Long-term nitric oxide release and elevated temperature stability with S-nitroso-N-acetylpenicillamine (SNAP)-doped Elast-eon E2As polymer
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Nitric oxide (NO) is known to be a potent inhibitor of platelet activation and adhesion. Healthy endothelial cells that line the inner walls of all blood vessels exhibit a NO flux of 0.5-4 × 10(-10) mol cm(-2) min(-1) that helps prevent thrombosis. Materials with a NO flux that is equivalent to this level are expected to exhibit similar anti-thrombotic properties. In this study, five biomedical grade polymers doped with S-nitroso-N-acetylpenicillamine (SNAP) were investigated for their potential to control the release of NO from the SNAP within the polymers, and further control the release of SNAP itself. SNAP in the Elast-eon E2As polymer creates an inexpensive, homogeneous coating that can locally deliver NO (via thermal and photochemical reactions) as well slowly release SNAP. Furthermore, SNAP is surprisingly stable in the E2As polymer, retaining 82% of the initial SNAP after 2 months storage at 37 °C. The E2As polymer containing SNAP was coated on the walls of extracorporeal circulation (ECC) circuits and exposed to 4 h blood flow in a rabbit model of extracorporeal circulation to examine the effects on platelet count, platelet function, clot area, and fibrinogen adsorption. After 4 h, platelet count was preserved at 100 ± 7% of baseline for the SNAP/E2As coated loops, compared to 60 ± 6% for E2As control circuits (n = 4). The SNAP/E2As coating also reduced the thrombus area when compared to the control (2.3 ± 0.6 and 3.4 ± 1.1 pixels/cm(2), respectively). The results suggest that the new SNAP/E2As coating has potential to improve the thromboresistance of intravascular catheters, grafts, and other blood-contacting medical devices, and exhibits excellent storage stability compared to previously reported NO release polymeric materials.
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Because of the large blood-contacting surface area in extracorporeal circulation, loss of platelet count and platelet functionality is significant.
“Due to the large surfaces area that is in contact with blood in extracorporeal circulation (ECC), the loss of platelet count and platelet functionality are significant,161 and many researchers have developed NO releasing43,154,155,161,236,238,278,279 or NO generating254 polymeric ECC tubing to prevent platelet activation and consumption during this process (see Table 1).”
From Recent advances in thromboresistant and antimicrobial polymers for biomedical applications: just say yes to nitric oxide (NO) (2016) · cites this paper as [161]
SNAP-doped E2As polymer films exhibit unprecedented shelf-life stability, with 82% of the initial SNAP remaining after 2 months storage at 37 °C.
“Brisbois et al.161 were the first to discover that SNAP-doped E2As polymer films exhibit unprecedented shelf-life stability, with 82 % of the initial SNAP remaining after 2 months storage at 37 °C.”
From Recent advances in thromboresistant and antimicrobial polymers for biomedical applications: just say yes to nitric oxide (NO) (2016) · cites this paper as [161]
10 wt% SNAP/E2As films can release NO for up to 20 d at levels above the physiological NO flux range.
“The 10 wt% SNAP/E2As films can release NO for up to 20 d at levels above the physiological NO flux range.”
From Recent advances in thromboresistant and antimicrobial polymers for biomedical applications: just say yes to nitric oxide (NO) (2016) · cites this paper as [161]
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Cites
Estimation of nitric oxide production and reactionrates in tissue by use of a mathematical model
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Self-citationMediation of <i>in vivo</i> glucose sensor inflammatory response via nitric oxide release
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Self-citationYang, J., Welby, J. L., & Meyerhoff, M. E. (2008) · Langmuir · doi:10.1021/la801466e · Cited by 55 · see citing works
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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
Self-citationWo, Y., Li, Z., Brisbois, E. J., Colletta, A., Wu, J., Major, T. C., Xi, C., Bartlett, R. H., Matzger, A. J., & Meyerhoff, M. E. (2015) · ACS Applied Materials & Interfaces · doi:10.1021/acsami.5b07501 · Cited by 128 · see citing works
Self-citationBrisbois, E. J., Davis, R. P., Jones, A. M., Major, T. C., Bartlett, R. H., Meyerhoff, M. E., & Handa, H. (2015) · Journal of Materials Chemistry B · doi:10.1039/c4tb01839g · Cited by 101 · see citing works
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-citationHanda, H., Major, T. C., Brisbois, E. J., Amoako, K. A., Meyerhoff, M. E., & Bartlett, R. H. (2014) · J. Mater. Chem. B · doi:10.1039/c3tb21771j · Cited by 64 · see citing works
Self-citationMajor, T. C., Handa, H., Annich, G. M., & Bartlett, R. H. (2014) · Journal of Biomaterials Applications · doi:10.1177/0885328214538866 · Cited by 43 · see citing works
Self-citationWolf, A. K., Qin, Y., Major, T. C., & Meyerhoff, M. E. (2015) · Chinese Chemical Letters · doi:10.1016/j.cclet.2015.03.002 · Cited by 21 · see citing works
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- Authors
- Brisbois, E. J., Handa, H., Major, T. C., Bartlett, R. H., & Meyerhoff, M. E.
- Affiliations
- University of Michigan (US)
- Corresponding author
- Meyerhoff, Mark E.
- Venue
- Biomaterials
- Publisher
- Elsevier BV
- Published
- 2013-09
- Volume
- 34
- Issue
- 28
- Pages
- 6957-6966
- ISSN
- 0142-9612 (ISSN-L)
- PMC
- PMC3729938
- OpenAlex
- W2075453630
- Cited by
- 165
- References
- 6
- Citations by year
- 2026: 8 · 2025: 12 · 2024: 11 · 2023: 18 · 2022: 13 · 2021: 16 · 2020: 11 · 2019: 20 · 2018: 12 · 2017: 13 · 2016: 11 · 2015: 13 · 2014: 5 · 2013: 1
- FWCI
- 3.96
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Biomaterials (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health (EB-004527, K25HL111213)
- Topics
- Physical Sciences › Materials Science › Surfaces, Coatings and Films › Polymer Surface Interaction Studies
- Health Sciences › Medicine › Physiology › Nitric Oxide and Endothelin Effects
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Medicine › Hydrogels: synthesis, properties, applications
- Keywords
- nitric oxide release, S-nitroso-N-acetylpenicillamine, SNAP, extracorporeal circuit, thromboresistance, platelet activation, platelet count, thrombus formation, fibrinogen adsorption, blood-contacting devices, storage stability
- MeSH terms
- Animals, Nitric Oxide, Platelet Aggregation, Polymers, Rabbits, Temperature, S-Nitroso-N-Acetylpenicillamine
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