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

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• 作者：Elizabeth J. Brisbois^a ; Terry C. Major^a ; Marcus J. Goudie^b ; Robert H. Bartlett^a ; Mark E. Meyerhoff^c ; Hitesh Handa^b ; ^{hhanda@uga.edu" class="auth_mail" title="E-mail the corresponding author}
• 关键词：Blood compatibility ; Extracorporeal circulation ; Nitric oxide delivery ; S-Nitrosothiols ; Thrombosis
• 刊名：Acta Biomaterialia
• 出版年：2016
• 出版时间：June 2016
• 年：2016
• 卷：37
• 期：Complete
• 页码：111-119
• 全文大小：1011 K

文摘

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 × 10⁻¹⁰ mol cm⁻² min⁻¹, which mimics the range of NO release from the normal endothelium, which is stable for at least 4 h. 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 4 h 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.

Statement of Significance

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. These NO-releasing ECCs were able to attenuate the activation of platelets and maintain their functionality, while significantly reducing the extent of thrombus formation during 4 h blood flow in the rabbit model of thrombogenicity.