Nitric oxide-releasing polyurethanes

1 University of Georgia, Athens, GA, USA University of Michigan Medical Center, Ann Arbor, Ml, USA 

Infection and foreign body response (FBR) are among other significant problems faced by long-term use of medical devices. The mechanism of bacterial adhesion is a very complex process. Bacterial adhesion involves initial reversible physicochemical interactions, followed by time-dependent irreversible molecular and cellular interactions (An and Friedman, 2000). Due to various physical forces, such as Brownian movement, van der Waals forces, and hydrophobic and electrostatic interactions, bacteria move to the implant surface. In the second phase, molecular and cellular interactions become predominant where bacteria attach irreversibly to the surface 

Radomski et al. first described NO as a potent vasodilator secreted by the normal endothelium that has the ability to inhibit platelet adhesion and aggregation to the blood vessel wall (Radomski et al., 1987 Radomski and Moncada, 1993a). In 1992, the free radical NO received approbation as molecule of the year by the journal Science and was the subject of a Nobel Prize. Numerous published reviews have been devoted to a comprehensive discussion of different NO-releasing/generating materials and their many potential biomedical applications (Frost et al., 2005 Seabra et al., 2012 Riccio and Schoenfisch, 2012 Kim et al., 2014 Jen et al., 2012 Halpenny and Mascharak, 2010 Carpenter and Schoenfisch, 2012). 

PUs offer several applications in blood-contacting devices. Many strategies have been studied to create localized NO release/generation from various PU materials. As discussed above, NORel polymers are prepared by covalently or noncovalently incorporating NO donor molecules into polymer matrices. Diazeniumdiolates have been incorporated into polymers for a variety of potential applications. Taite et al.. 

These examples demonstrate the various chemistries that have been used to incorporate NO-releasing/generating materials in medical grade PUs. Below are specific examples of NO-releasing/generating PUs that have been examined for some specific biomedical applications. 

---

Reynolds MM, Hrabie JA, Oh BK, Politis JK, Citro ML, Keefer LK, et al. Nitric oxide releasing polyurethanes with covalently linked diazeniumdiolated secondary amines. Biomacromolecules 2006 7 987-94. http //dx.doi.org/10.1021/bm060028o. 

Coneski PN, Schoenflsch MH. Synthesis of nitric oxide-releasing polyurethanes with 5-nitrosothiol-containing hard and soft segments. Polym Chem 2011 2 906-13. http //dx.doi.Org/10.1039/c0py00269k. 

Biomedical applications of nitric oxide-releasing polyurethanes... 

Koh, A., Riccio, D.A., Sun, B., Carpenter, A.W., Nichols, S.P., Schoenfisch, M.H., 2011b. Fabrication of nitric oxide-releasing polyurethane glucose sensor membranes. Biosensors and Bioelectronics 28, 17—24. 

Taite, L.J., Yang, R, Jun, H.W., West, J.L., 2008. Nitric oxide-releasing polyurethane-PEG copolymer containing the YIGSR peptide promotes endothelialization with decreased platelet adhesion. Journal of Biomedical Materials Research Part B Applied Biomaterials... 

---