Improved hemocompatibility of silicone rubber extracorporeal tubing via solvent swelling-impregnation of S-nitroso-N-acetylpenicillamine (SNAP) and evaluation in rabbit thrombogenicity model

• Published in: Acta biomaterialia 2016-06, Vol.37, p.111-119
• Main Authors: Brisbois, Elizabeth J., Major, Terry C., Goudie, Marcus J., Bartlett, Robert H., Meyerhoff, Mark E., Handa, Hitesh
• Format: Article
• Language: English
• Subjects: Activation; Animals; Blood compatibility; Blood Platelets - drug effects; Circuits; Disease Models, Animal; Extracorporeal circulation; Extracorporeal Circulation - instrumentation; Hemodynamics - drug effects; Materials Testing - methods; Microscopy, Electron, Scanning; Nitric Oxide - metabolism; Nitric oxide delivery; Platelets; Polymers; Rabbits; S-Nitroso-N-Acetylpenicillamine - therapeutic use; S-Nitrosothiols; Silicone Elastomers - chemistry; Silicone rubber; SNAP; Solvents; Solvents - chemistry; Swelling; Thrombosis; Thrombosis - drug therapy; Thrombosis - pathology; Thrombosis - physiopathology; Time Factors
• ISSN: 1742-7061; 1878-7568
• DOI: 10.1016/j.actbio.2016.04.025

Silicone rubber (SR) tubing is soaked in a swelling solution to impregnate the entire tubing wall with S-nitroso-N-acetylpenicillamine (SNAP). The SNAP-silicone rubber tubing is used to fabricate extracorporeal circulation (ECC) loops that delivers nitric oxide (NO), a potent inhibitor of platelet adhesion/activation, and can significantly reduce thrombosis in a rabbit model of thrombogenicity. [Display omitted] Blood-contacting devices, including extracorporeal circulation (ECC) circuits, can suffer from complications due to platelet activation and thrombus formation. Development of nitric oxide (NO) releasing polymers is one method to improve hemocompatibility, taking advantage of the ability of low levels of NO to prevent platelet activation/adhesion. In this study a novel solvent swelling method is used to load the walls of silicone rubber tubing with the NO donor S-nitroso-N-acetylpenicillamine (SNAP). This SNAP-silicone rubber tubing exhibits an NO flux of ca. 1×10−10molcm−2min−1, which mimics the range of NO release from the normal endothelium, which is stable for at least 4h. Images of the tubing before and after swelling, obtained via scanning electron microscopy, demonstrate that this swelling method has little effect on the surface properties of the tubing. The SNAP-loaded silicone rubber and silicone rubber control tubing are used to fabricate ECC circuits that are evaluated in a rabbit model of thrombogenicity. After 4h of blood flow, the SNAP-loaded silicone rubber circuits were able to preserve the blood platelet count at 64% of baseline (vs. 12% for silicone rubber control). A 67% reduction in the degree of thrombus formation within the thrombogenicity chamber was also observed. This study demonstrates the ability to improve the hemocompatibility of existing/commercial silicone rubber tubing via a simple solvent swelling-impregnation technique, which may also be applicable to other silicone-based blood-contacting devices. Localized nitric oxide (NO) release can be achieved from biomedical grade polymers doped with S-nitroso-N-acetylpenicillamine (SNAP). Despite the promising in vitro and in vivo biocompatibility results reported for these NO releasing polymers, many of these materials may face challenges in being translated to clinical applications, especially in the areas of polymer processing and manufacturing. In this study, we report a solvent swelling-impregnation technique to incorporate SNAP into extracorporeal circuit (ECC) tubing.