Preparation and characterization of polymeric coatings with combined nitric oxide release and immobilized active heparin
Abstract
A new dual acting polymeric coating is described that combines nitric oxide (NO) release with surface-bound active heparin, with the aim of mimicking the nonthrombogenic properties of the endothelial cell (EC) layer that lines the inner wall of healthy blood vessels. A trilayer membrane configuration is employed to create the proposed blood compatible coating. A given polymeric substrate (e.g., the outer surface of a catheter sleeve, etc.) is first coated with a dense polymer layer, followed by a plasticized poly(vinyl chloride) (PVC) or polyurethane (PU) layer doped with a lipophilic N-diazeniumdiolate as the NO donor species. Finally, an outer aminated polymer layer is applied. Porcine heparin is then covalently linked to the outer layer via formation of amide bonds. The surface-bound heparin is shown to possess anti-coagulant activity in the range of 4.80-6.39 mIU/cm2 as determined by a chromogenic anti-Factor Xa assay. Further, the surface NO flux from the underlying polymer layer containing the diazeniumdiolate species can be controlled and maintained at various levels (from 0.5 to 60 x 10(-10) mol cm(-2)min(-1)) for at least 24 h and up to 1 week (depending on the flux level desired) by changing the chemical/polymer composition of the NO release layer. The proposed polymeric coatings are capable of functioning by two complementary anti-thrombotic mechanisms, one based on the potent anti-platelet activity of NO, and the other the result of the ability of immobilized heparin to inhibit Factor Xa and thrombin (Factor IIa). Thus, the proposed polymeric coatings are expected to exhibit greatly enhanced thromboresistivity compared to polymers that utilize either immobilized heparin or NO release alone.
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Considerable effort has been devoted to developing combination therapy and hybrid drugs that combine NO release functionality with other active agents for increased efficacies, including anticoagulants, direct thrombin inhibitors, antimicrobial metal ions, quaternary ammonium compounds, PEG, antibiotics, and NSAIDs.
“Recently, considerable effort has been devoted to develop combination therapy and hybrid drugs that combine NO release functionality with other active agents for increased efficacies, including anticoagulants,35,126 direct thrombin inhibitors,36,43 antimicrobial metal ions,215 quaternary ammonium compounds,70 PEG,115 antibiotics,296 and non-steroidal anti-inflammatory drugs (NSAIDs), such as ibu”
From Recent advances in thromboresistant and antimicrobial polymers for biomedical applications: just say yes to nitric oxide (NO) (2016) · cites this paper as [35]
Cites
The coagulation cascade: initiation, maintenance, and regulation
Davie, E. W., Fujikawa, K., & Kisiel, W. (1991) · Biochemistry · doi:10.1021/bi00107a001 · Cited by 1,821 · see citing works
Nitric oxide donors: chemical activities and biological applications
Wang, P. G., Xian, M., Tang, X., Wu, X., Wen, Z., Cai, T., & Janczuk, A. J. (2002) · Chemical Reviews · doi:10.1021/cr000040l · Cited by 1,337 · see citing works
New Challenges in Biomaterials
Peppas, N. A., & Langer, R. (1994) · Science · doi:10.1126/science.8134835 · Cited by 1,145 · see citing works
Michiels, C. (2003) · Journal of Cellular Physiology · doi:10.1002/jcp.10333 · Cited by 774 · see citing works
Lüscher, T. F., & Barton, M. (1997) · Clinical Cardiology · doi:10.1002/j.1932-8737.1997.tb00006.x · Cited by 537 · see citing works
Biomaterials in the development and future of vascular grafts
Xue, L., & Greisler, H. P. (2003) · Journal of Vascular Surgery · doi:10.1067/mva.2003.88 · Cited by 519 · see citing works
Hrabie, J. A., & Keefer, L. K. (2002) · Chemical Reviews · doi:10.1021/cr000028t · Cited by 466 · see citing works
A Method for the High Efficiency of Water-Soluble Carbodiimide-Mediated Amidation
Sehgal, D., & Vijay, I. K. (1994) · Analytical Biochemistry · doi:10.1006/abio.1994.1144 · Cited by 346 · see citing works
Frost, M. C., Reynolds, M. M., & Meyerhoff, M. E. (2005) · Biomaterials · doi:10.1016/j.biomaterials.2004.06.006 · Cited by 343 · see citing works
Self-citationColorimetric method for the assay of heparin content in immobilized heparin preparations
Smith, P. K., Mallia, A. K., & Hermanson, G. T. (1980) · Analytical Biochemistry · doi:10.1016/0003-2697(80)90679-x · Cited by 318 · see citing works
Immobilization of heparin to EDC/NHS-crosslinked collagen. Characterization and in vitro evaluation
Wissink, M., Beernink, R. H. J., Pieper, J., Poot, A. A., Engbers, G. H. M., Beugeling, T., van Aken, W. G., & Feijén, J. (2001) · Biomaterials · doi:10.1016/s0142-9612(00)00164-2 · Cited by 313 · see citing works
Assay of heparin in plasma using a chromogenic substrate for activated factor X
Teien, A. N., Lie, M., & Abildgaard, U. (1976) · Thrombosis Research · doi:10.1016/0049-3848(76)90034-7 · Cited by 293 · see citing works
Loscalzo, J., & Schafer, A. I. (2002) · Cited by 291 · see citing works
Teien, A. N., & Lie, M. (1977) · Thrombosis Research · doi:10.1016/0049-3848(77)90150-5 · Cited by 290 · see citing works
Kwaan, H. C. (2003) · JAMA · doi:10.1001/jama.289.22.3014-b · Cited by 240 · see citing works
Heparin immobilization onto segmented polyurethaneurea surfaces—effect of hydrophilic spacers
Park, K. D., Okano, T., Nojiri, C., & Kim, S. W. (1988) · Journal of Biomedical Materials Research · doi:10.1002/jbm.820221103 · Cited by 228 · see citing works
Mowery, K. A., H. Schoenfisch, M., Saavedra, J. E., Keefer, L. K., & Meyerhoff, M. E. (2000) · Biomaterials · doi:10.1016/s0142-9612(99)00127-1 · Cited by 219 · see citing works
Self-citationNitric Oxide-Releasing Polymers Containing the [N(O)NO]<sup>-</sup>Group
Smith, D. J., Chakravarthy, D., Pulfer, S., Simmons, M. L., Hrabie, J. A., Citro, M. L., Saavedra, J. E., Davies, K. M., Hutsell, T. C., Mooradian, D. L., et al. (1996) · Journal of Medicinal Chemistry · doi:10.1021/jm950652b · Cited by 208 · see citing works
Davies, K. M., Wink, D. A., Saavedra, J. E., & Keefer, L. K. (2001) · Journal of the American Chemical Society · doi:10.1021/ja002899q · Cited by 208 · see citing works
Brash, J. L. (2000) · Journal of Biomaterials Science Polymer Edition · doi:10.1163/156856200744237 · Cited by 201 · see citing works
Progress Toward Clinical Application of the Nitric Oxide–Releasing Diazeniumdiolates
Keefer, L. K. (2003) · The Annual Review of Pharmacology and Toxicology · doi:10.1146/annurev.pharmtox.43.100901.135831 · Cited by 189 · see citing works
Zhang, H., Annich, G. M., Miskulin, J., Stankiewicz, K., Osterholzer, K., Merz, S. I., Bartlett, R. H., & Meyerhoff, M. E. (2003) · Journal of the American Chemical Society · doi:10.1021/ja0291538 · Cited by 176 · see citing works
Self-citationNitric oxide-generating polymers reduce platelet adhesion and smooth muscle cell proliferation
Bohl, K. S., & West, J. L. (2000) · Biomaterials · doi:10.1016/s0142-9612(00)00153-8 · Cited by 174 · see citing works
Kang, I., Kwon, O. H., Lee, Y. M., et al. (1996) · Biomaterials · doi:10.1016/0142-9612(96)81422-0 · Cited by 172 · see citing works
Zhang, H., Annich, G. M., Miskulin, J., Osterholzer, K., Merz, S. I., Bartlett, R. H., & Meyerhoff, M. E. (2002) · Biomaterials · doi:10.1016/s0142-9612(01)00274-5 · Cited by 168 · see citing works
Self-citationDesigning Biostable Polyurethane Elastomers for Biomedical Implants
Gunatillake, P. A., Martin, D. J., Meijs, G. F., McCarthy, S. J., & Adhikari, R. (2003) · Australian Journal of Chemistry · doi:10.1071/ch02168 · Cited by 160 · see citing works
Balakrishnan, B., Kumar, D. S., Yoshida, Y., & Jayakrishnan, A. (2005) · Biomaterials · doi:10.1016/j.biomaterials.2004.09.032 · Cited by 157 · see citing works
Annich, G. M., Meinhardt, J. P., Mowery, K. A., Ashton, B. A., Merz, S. I., Hirschl, R. B., Meyerhoff, M. E., & Bartlett, R. H. (2000) · Critical Care Medicine · doi:10.1097/00003246-200004000-00001 · Cited by 152 · see citing works
Self-citationAngiotensin‐II receptors: new targets for antihypertensive therapy
Oliverio, M. I., & Coffman, T. M. (1997) · Clinical Cardiology · doi:10.1002/clc.4960200103 · Cited by 122 · see citing works
Schoenfisch, M. H., Mowery, K. A., Rader, M. V., Baliga, N., Wahr, J. A., & Meyerhoff, M. E. (2000) · Analytical Chemistry · doi:10.1021/ac991370c · Cited by 121 · see citing works
Self-citationBatchelor, M. M., Reoma, S. L., Fleser, P. S., Nuthakki, V. K., Callahan, R. E., Shanley, C. J., Politis, J. K., Elmore, J., Merz, S. I., & Meyerhoff, M. E. (2003) · Journal of Medicinal Chemistry · doi:10.1021/jm030286t · Cited by 120 · see citing works
Self-citationEspadas-Torre, C., & Meyerhoff, M. E. (1995) · Analytical Chemistry · doi:10.1021/ac00114a003 · Cited by 117 · see citing works
Self-citationReynolds, M. M., Frost, M. C., & Meyerhoff, M. E. (2004) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2004.06.019 · Cited by 116 · see citing works
Self-citationSurface modification of PVC endotracheal tubes by oxygen glow discharge to reduce bacterial adhesion
Balazs, D. J., Triandafillu, K., Chevolot, Y., et al. (2003) · Surface and Interface Analysis · doi:10.1002/sia.1533 · Cited by 110 · see citing works
Keefer, L. K., Flippen-Anderson, J. L., George, C. F., Shanklin, A. P., Dunams, T. M., Christodoulou, D., Saavedra, J. E., Sagan, E. S., & Bohle, D. S. (2001) · Nitric Oxide · doi:10.1006/niox.2001.0359 · Cited by 94 · see citing works
Synthesis and Characterization of Polymethacrylate-Based Nitric Oxide Donors
Parzuchowski, P. G., Frost, M. C., & Meyerhoff, M. E. (2002) · Journal of the American Chemical Society · doi:10.1021/ja020268l · Cited by 93 · see citing works
Self-citationFrost, M. C., Rudich, S. M., Zhang, H., Maraschio, M., & Meyerhoff, M. E. (2002) · Analytical Chemistry · doi:10.1021/ac025944g · Cited by 93 · see citing works
Self-citationOn the blood compatibility of end-point immobilized heparin
Olsson, P., Sánchez, J., Mollnes, T. E., & Riesenfeld, J. (2000) · Journal of Biomaterials Science Polymer Edition · doi:10.1163/156856200744192 · Cited by 89 · see citing works
Nitric oxide and platelet function: Implications for neonatology
Cheung, P., Salas, E., Schulz, R., & Radomski, M. W. (1997) · Seminars in Perinatology · doi:10.1016/s0146-0005(97)80006-7 · Cited by 88 · see citing works
Heparin release from thermosensitive polymer coatings: <i>in vivo</i> studies
Gutowska, A., Bae, Y. H., Jacobs, H., Mohammad, F., Mix, D., Feijen, J., & Kim, S. W. (1995) · Journal of Biomedical Materials Research · doi:10.1002/jbm.820290705 · Cited by 76 · see citing works
Keefer, L. K. (2003) · Nature Materials · doi:10.1038/nmat913 · Cited by 74 · see citing works
Design of Nonthrombogenic Polymer Surfaces for Blood-Contacting Medical Devices
Kim, S. W., & Jacobs, H. A. (2008) · Blood Purification · doi:10.1159/000170288 · Cited by 73 · see citing works
The antiplatelet activity of immobilized prostacyclin
Ebert, C., Lee, E. S., & Kim, S. (1982) · Journal of Biomedical Materials Research · doi:10.1002/jbm.820160510 · Cited by 69 · see citing works
Thromboresistant Chemical Sensors Using Combined Nitric Oxide Release/Ion Sensing Polymeric Films
Espadas-Torre, C., Oklejas, V., Mowery, K. A., & Meyerhoff, M. E. (1997) · Journal of the American Chemical Society · doi:10.1021/ja963054a · Cited by 69 · see citing works
Self-citationSynthesis and characterization of SPUU–PEO–heparin graft copolymers
Park, K. D., Piao, A. Z., Jacobs, H. A., Okano, T., & Kim, S. W. (1991) · Journal of Polymer Science Part A Polymer Chemistry · doi:10.1002/pola.1991.080291206 · Cited by 66 · see citing works
Blood compatibility of SUUU‐PEO‐heparin graft copolymers
Park, K. D., Kim, W. G., Jacobs, H. A., et al. (1992) · Journal of Biomedical Materials Research · doi:10.1002/jbm.820260605 · Cited by 60 · see citing works
Kishida, A., Ueno, Y., Fukudome, N., et al. (1994) · Biomaterials · doi:10.1016/0142-9612(94)90041-8 · Cited by 53 · see citing works
Biomaterials Engineering and Devices: Human Applications
Wise, D. L. (2000) · Humana Press eBooks · doi:10.1007/978-1-59259-197-8 · Cited by 45 · see citing works
Zhou, Z., & Meyerhoff, M. E. (2005) · Biomacromolecules · doi:10.1021/bm049462l · Cited by 36 · see citing works
Self-citationBioactive heparin surfaces from derivatization of polyacrylamide-grafted LLDPE
Wirsén, A., Ohrlander, M., & Albertsson, A. (1996) · Biomaterials · doi:10.1016/0142-9612(95)00306-1 · Cited by 35 · see citing works
Ching., S., & Meyerhoff, M. E. (1990) · Microchimica Acta · doi:10.1007/bf01244842 · Cited by 34 · see citing works
Self-citationKishida, A., Ueno, Y., Maruyama, I., et al. (1994) · Biomaterials · doi:10.1016/0142-9612(94)90238-0 · Cited by 32 · see citing works
Immobilization of Human Thrombomodulin to Expanded Polytetrafluoroethylene
Li, J., Singh, M. J., Nelson, P. R., et al. (2002) · Journal of Surgical Research · doi:10.1006/jsre.2002.6381 · Cited by 31 · see citing works
The antithrombotic effect of prostaglandin E1 immobilized on albuminated polymer matrix
Chandy, T., & Sharma, C. P. (1984) · Journal of Biomedical Materials Research · doi:10.1002/jbm.820180913 · Cited by 28 · see citing works
Davies, K. M., Wink, D. A., Saavedra, J. E., & Keefer, L. K. (2001) · ChemInform · doi:10.1002/chin.200136073 · Cited by 28 · see citing works
Jc, M., & Sw, K. (1978) · PubMed · Cited by 28 · see citing works
Surface modification of poly(vinyl chloride) for antithrombogenicity study
Xie, Y., & Yang, Q. (2002) · Journal of Applied Polymer Science · doi:10.1002/app.10483 · Cited by 27 · see citing works
Jacobs, H. A., Okano, T., & Kim, S. W. (1989) · Journal of Biomedical Materials Research · doi:10.1002/jbm.820230606 · Cited by 25 · see citing works
Saavedra, J. E., Mooradian, D. L., Mowery, K. A., Schoenfisch, M. H., Citro, M. L., Davies, K. M., Meyerhoff, M. E., & Keefer, L. K. (2000) · Bioorganic & Medicinal Chemistry Letters · doi:10.1016/s0960-894x(00)00086-x · Cited by 21 · see citing works
Self-citationPGE1—Heparin conjugate releasing polymers
Jacobs, H. A., Okano, T., Lin, J. Y., et al. (1985) · Journal of Controlled Release · doi:10.1016/0168-3659(85)90053-7 · Cited by 19 · see citing works
The good, the bad and the obvious: 1993 Clemson Award for basic research—Keynote lecture
Sefton, M. V. (1993) · Biomaterials · doi:10.1016/0142-9612(93)90155-u · Cited by 16 · see citing works
Modification of Biomaterials to Improve Blood Compatibility
Bamford, C. H., Middleton, L., Al-Lamee, K. G., & Paprotny, J. (1992) · The International Journal of Artificial Organs · doi:10.1177/039139889201500202 · Cited by 7 · see citing works
Poly(Butanediol Spermate): A Hydrolytically Labile Polyester-Based Nitric Oxide Carrier
Rao, W., & Smith, D. J. B. (1999) · Journal of Bioactive and Compatible Polymers · doi:10.1177/088391159901400106 · Cited by 2 · see citing works
Superior performance of thrombomodulin coated small caliber ePTFE grafts
Lo, C., Li, J., Nelson, P. R., et al. (2003) · Journal of Surgical Research · doi:10.1016/j.jss.2003.08.204 · Cited by 2 · see citing works
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Self-citationPolymer‐Based Nitric Oxide Therapies: Recent Insights for Biomedical Applications
Jen, M. C., Serrano, M. C., van Lith, R., & Ameer, G. A. (2012) · Advanced Functional Materials · doi:10.1002/adfm.201101707 · Cited by 194 · see citing works
Wu, B., Gerlitz, B., Grinnell, B. W., & Meyerhoff, M. E. (2007) · Biomaterials · doi:10.1016/j.biomaterials.2007.06.002 · Cited by 102 · see citing works
Self-citationMajor, T. C., Brisbois, E. J., Jones, A. M., Zanetti, M. E., Annich, G. M., Bartlett, R. H., & Handa, H. (2014) · Biomaterials · doi:10.1016/j.biomaterials.2014.05.036 · Cited by 83 · see citing works
Hwang, S., & Meyerhoff, M. E. (2008) · Biomaterials · doi:10.1016/j.biomaterials.2008.02.004 · Cited by 82 · see citing works
Self-citationWu, Y., & Meyerhoff, M. E. (2008) · Talanta · doi:10.1016/j.talanta.2007.06.022 · Cited by 65 · see citing works
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Yang, J., Welby, J. L., & Meyerhoff, M. E. (2008) · Langmuir · doi:10.1021/la801466e · Cited by 55 · see citing works
Self-citationWang, Y., Chen, S., Pan, Y., Gao, J., Tang, D., Kong, D., & Wang, S. (2015) · Journal of Materials Chemistry B · doi:10.1039/c5tb02080h · Cited by 50 · see citing works
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- Authors
- Zhou, Z., & Meyerhoff, M. E.
- Affiliations
- University of Michigan (US)
- Corresponding author
- Meyerhoff, Mark E.
- ORCID
- Meyerhoff, Mark E.
- Venue
- Biomaterials
- Publisher
- Elsevier BV
- Published
- 2005-11
- Volume
- 26
- Issue
- 33
- Pages
- 6506-6517
- ISSN
- 0142-9612 (ISSN-L)
- OpenAlex
- W2006883085
- Cited by
- 115
- References
- 64
- Citations by year
- 2026: 2 · 2024: 3 · 2023: 6 · 2022: 2 · 2021: 8 · 2020: 13 · 2019: 5 · 2018: 3 · 2017: 4 · 2016: 8 · 2015: 4 · 2014: 11 · 2013: 7 · 2012: 5
- FWCI
- 3.40
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Biomaterials (publishedVersion)
- PubMed (publishedVersion)
- Funders
- University of Michigan
- National Institutes of Health
- National Institute of Biomedical Imaging and Bioengineering (EB 00783, R01EB000783)
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (HD-015434, R01HD015434)
- Topics
- Physical Sciences › Materials Science › Surfaces, Coatings and Films › Polymer Surface Interaction Studies
- Health Sciences › Medicine › Physiology › Nitric Oxide and Endothelin Effects
- Health Sciences › Medicine › Hematology › Blood Coagulation and Thrombosis Mechanisms
- Keywords
- nitric oxide release, polymer coatings, antithrombotic coatings, N-diazeniumdiolates, polyvinyl chloride, polyurethane, anti-Xa activity, thrombin inhibition, antiplatelet activity, catheter coatings, thromboresistance
- MeSH terms
- Animals, Antibodies, Anticoagulants, Biocompatible Materials, Electron Probe Microanalysis, Heparin, Models, Chemical, Nitric Oxide, Magnetic Resonance Spectroscopy, Polymers, Polyurethanes, Polyvinyl Chloride, Surface Properties, Swine, Thrombin, Time Factors, Toluidines, Vinyl Chloride, Factor Xa, Spectroscopy, Fourier Transform Infrared, Nitric Oxide Donors, Coated Materials, Biocompatible
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