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Polymeric coatings that mimic the endothelium: Combining nitric oxide release with surface-bound active thrombomodulin and heparin
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Multi-functional bilayer polymeric coatings are prepared with both controlled nitric oxide (NO) release and surface-bound active thrombomodulin (TM) alone or in combination with immobilized heparin. The outer-layer is made of CarboSil, a commercially available copolymer of silicone rubber (SR) and polyurethane (PU). The CarboSil is either carboxylated or aminated via an allophanate reaction with a diisocyanate compound followed by a urea-forming reaction between the generated isocyanate group of the polymer and the amine group of an amino acid (glycine), an oligopeptide (triglycine) or a diamine. The carboxylated CarboSil can then be used to immobilize TM through the formation of an amide bond between the surface carboxylic acid groups and the lysine residues of TM. Aminated CarboSil can also be employed to initially couple heparin to the surface, and then the carboxylic acid groups on heparin can be further used to anchor TM. Both surface-bound TM and heparin's activity are evaluated by chromogenic assays and found to be at clinically significant levels. The underlying NO release layer is made with another commercial SR-PU copolymer (PurSil) mixed with a lipophilic NO donor (N-diazeniumdiolated dibutylhexanediamine (DBHD/N(2)O(2))). The NO release rate can be tuned by changing the thickness of top coatings, and the duration of NO release at physiologically relevant levels can be as long as 2 weeks. The combination of controlled NO release as well as immobilized active TM and heparin from/on the same polymeric surface mimics the highly thromboresistant endothelium layer. Hence, such multifunctional polymer coatings should provide more blood-compatible surfaces for biomedical devices.
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“Other anticoagulants such as thrombomodulin,36 direct thrombin inhibitors (e.g., hirudin42 and argatroban43), or antiplatelet drugs (e.g.: prostacyclin (PGI2))36,41,42 have also been immobilized onto polymer surfaces to increase their hemocompatibility, with varying degrees of success.”
From Recent advances in thromboresistant and antimicrobial polymers for biomedical applications: just say yes to nitric oxide (NO) (2016) · cites this paper as [36]
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“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 [36]
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Lukas, K., Stadtherr, K., Gessner, A., Wehner, D., Schmid, T. M., Wendel, H. P., Schmid, Ç., & Lehle, K. (2017) · Materials · doi:10.3390/ma10040335 · Cited by 2
Improving the hemocompatibility of catheters via NO release/generation
Wo, Y., Brisbois, E. J., Bartlett, R. H., & Meyerhoff, M. E. (2017) · Elsevier eBooks · doi:10.1016/b978-0-08-100497-5.00013-6 · Cited by 2
Self-citationDevelopment of hemocompatible polymeric materials for blood-contacting medical devices
Wu, B. (2009) · Deep Blue (University of Michigan) · Cited by 2
Self-citationKador, K. E. (2010) · Lincoln (University of Nebraska) · Cited by 1
NOS-based biopolymers; towards novel thromboresistant no -release materials
Diwan, C. A. (2009) · Europe PMC (PubMed Central)
Expression and Characterization of Protein Chimera with Embedded Activated Protein C Generation
Schneider, M. (2011) · Lincoln (University of Nebraska)
Stent coatings for blood compatibility
Udipi, K. (2015) · Elsevier eBooks · doi:10.1016/b978-1-78242-105-4.00006-7
Design and Synthesis of Antithrombotic Liposomal Protein Conjugate
Zhang, H. (2012) · OhioLink ETD Center (Ohio Library and Information Network)
Metadata
- Authors
- Wu, B., Gerlitz, B., Grinnell, B. W., & Meyerhoff, M. E.
- Affiliations
- University of Michigan (US)
- Eli Lilly (United States) (US)
- Corresponding author
- Meyerhoff, Mark E.
- ORCID
- Meyerhoff, Mark E.
- Venue
- Biomaterials
- Publisher
- Elsevier BV
- Published
- 2007-10
- Volume
- 28
- Issue
- 28
- Pages
- 4047-4055
- ISSN
- 0142-9612 (ISSN-L)
- PMC
- PMC1986713
- OpenAlex
- W1973873605
- Cited by
- 102
- References
- 30
- Citations by year
- 2026: 1 · 2025: 1 · 2024: 4 · 2023: 5 · 2022: 3 · 2021: 7 · 2020: 9 · 2019: 1 · 2018: 4 · 2017: 7 · 2016: 5 · 2015: 9 · 2014: 6 · 2013: 7 · 2012: 6
- FWCI
- 3.12
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Biomaterials (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- University of Michigan
- National Institutes of Health
- Medical School, University of Michigan
- National Institute of Biomedical Imaging and Bioengineering (R01EB000783)
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (R01HD015434)
- Topics
- Physical Sciences › Materials Science › Surfaces, Coatings and Films › Polymer Surface Interaction Studies
- Health Sciences › Medicine › Physiology (medical) › Nitric Oxide and Endothelin Effects
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmaceutical Science › Advanced Drug Delivery Systems
- Keywords
- nitric oxide release, thrombomodulin, heparin immobilization, surface functionalization, thromboresistance, hemocompatibility, controlled drug release
- MeSH terms
- Blood, Endothelium, Heparin, Humans, Materials Testing, Nitric Oxide, Polycarboxylate Cement, Polymers, Polyurethanes, Protein Binding, Silicones, Surface Properties, Molecular Structure, Thrombomodulin, Coated Materials, Biocompatible
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