Advances in Polyurethane Biomaterials. http://dx.doi.org/10.1016/B978-0-08-100614-6.00014-7 Copyright © 2016 Elsevier Ltd. All rights reserved. Nitric oxide-releasing polyurethanes J. Pant 1 , M.J. Goudie 1 , E.J. Brisbois 2 , H. Handa 1, * 1 University of Georgia, Athens, GA, USA; 2 University of Michigan Medical Center, Ann Arbor, MI, USA *Corresponding author: hhanda@uga.edu 14 14.1 Introduction As a replacement for natural rubber, Dr Otto Bayer first discovered polyurethane (PU) during World War II. Since then, PUs have been used in biomedical applications due to their excellent stability, mechanical properties, and biocompatibility (Boretos and Pierce, 1968; Lyman et al., 1971). From 1995 to 2015, PUs have gained popularity in several blood-contacting device applications including synthetic conduits, extracorporeal life supports (ECLSs), intravascular stents, in vivo sensors, defibrillators, and intravascular catheters. Thrombosis is one of the primary problems associated with blood-contacting devices that can cause life-threatening complications for patients. The blood coagu- lation cascade is a complex process, where protein adsorption occurs within a few seconds to minutes when blood comes in contact with a foreign surface (Figure 14.1). This is followed by platelet adhesion and activation that finally leads to thrombus formation (Horbett, 1993). Adsorbed plasma proteins, such as fibrinogen, bind to glycoprotein GPIIb/IIIa receptors on activated platelets (Gorbet and Sefton, 2004). The activation of platelets also leads to conformation changes and the excretion of intracellular granulates containing adhesion molecules (P-selectin, coagulation factor V and VII, calcium ions, etc.), leading to additional adhesion and activation of plate- lets. From 1955 to 2015, much has been learned about blood–surface interactions, and many approaches have been studied to prevent thrombosis with systemic anticoagula- tion and surface modification. In a clinical setting, many of these devices require the use of anticoagulant therapies (e.g., heparin) to avoid device failure (Gaffney et al., 2010). Unfortunately, the long-term use of systemic anticoagulation can be harmful to the patient, and can result in bleeding, increased thrombosis, and thrombocytopenia (Ahanchi et al., 2007; Menajovsky, 2005; Robinson et al., 1993). 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 inter- actions (An and Friedman, 2000). Due to various physical forces, such as Brown- ian 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