Characterization and in vivo performance of nitric oxide‐releasing extracorporeal circuits in a feline model of thrombogenicity

Abstract

Infection and thrombosis are the two leading complications associated with blood contacting medical devices, and have led to the development of active materials that can delivery antibiotics or antithrombotic agents. Two key characteristics of these materials are the ability to produce controlled delivery, as well as minimal systemic delivery of the agent outside of the device site. Nitric oxide (NO) releasing materials are attractive as NO plays pivotal roles in the body's natural defense against bacterial infection, as well as regulation of platelet adhesion and activation. This work characterizes an NO-releasing extracorporeal circuit (ECC) under flow conditions for the first time, examining the effect of incubation and application of the top coating on leaching of NO donor and NO-release kinetics. Top coated ECCs with incubation delivered ca. 1% of the total NO potential over the 4-h period, whereas uncoated ECCs delivered over 4.5% of the total NO. Incubated ECC loops maintained a flux of 1.83 ± 0.50 × 10 mol min cm for the full 4 h duration. The NO-releasing ECC loops significantly increased the time-to-clot as compared to the corresponding control (11 ± 3.6 min control, 132 ± 93.0 min NO-releasing) when evaluated in vivo in a feline animal model. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 539-546, 2017.

Additively manufactured small‐diameter vascular grafts with improved tissue healing using a novel SNAP impregnation method

“…The partly penetrated morphology of S1 crystals into the grafts, which illustrate a possible firm attachment within SDVG bulk, can explain the same period of NO‐release from this structure compared with S2 crystals while the crystals were smaller in size compared to S2 crystals. It was reported in other studies that the long‐term release of NO is related to crystal stability within the polymer matrix which is in agreement with the results of NO‐release in the current study (Goudie, Brainard, et al, ).…”

“…Interestingly, the S1 crystals were dispersed more homogeneously and are in a broader range of sizes while the S2‐impregnated crystals are more similar in size. This microscale roughness of PLA after S2 impregnation is consistent with previous reports (Goudie, Brainard, Schmiedt, & Handa, ).…”

A multi-defense strategy: Enhancing bactericidal activity of a medical grade polymer with a nitric oxide donor and surface-immobilized quaternary ammonium compound

“…Water contact angles of control CarboSil, SNAP CarboSil, BPAM CarboSil, and SNAP-BPAM CarboSil surfaces are listed in Table 1. We have previously shown that due to lower water uptake of CarboSil, limited leaching of SNAP has been seen from SNAP doped CarboSil [71]. The study showed that leaching is further reduced with the use of a top coat as compared to the non-coated films.…”

“…Incorporation of SNAP to CarboSil has shown to provide continuous and localized NO delivery to specific sites of interest [70, 71]. The incorporation of SNAP in medical grade polymers have been shown to be hemocompatible and possesses stability during long-term storage at room temperature and physiological conditions [63, 72, 73].…”

S‐Nitroso‐N‐acetylpenicillamine impregnated endotracheal tubes for prevention of ventilator‐associated pneumonia

“…Nitric oxide (NO) is an endogenous gas that is released from the natural endothelium and is proven to be a strong antimicrobial agent (Brisbois et al, 2015; Brisbois, Major, Goudie, Bartlett et al, 2016; Sundaram, Pant, Goudie, Mani, & Handa, 2016). NO has a number of other biological function such as vasodilation, thrombosis, and aids in wound healing (Brisbois et al, 2015; Brisbois, Major, Goudie, Meyerhoff et al, 2016; Goudie, Brainard, Schmiedt, & Handa, 2017; Goudie et al, 2016). More specifically, NO that is released in the sinus cavities and by neutrophils and macrophages functions as an effective natural antiseptic agent (Brisbois et al, 2015; Degano, Genestal, Serrano, Rami, & Arnal, 2005).…”