Improved hemocompatibility of silicone rubber extracorporeal tubing via solvent swelling-impregnation of S-nitroso-N-acetylpenicillamine (SNAP) and evaluation in rabbit thrombogenicity model.
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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DOI：
10.1016/j.actbio.2016.04.025
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发表时间：
2016-06
影响因子：
9.7
通讯作者：
Handa H
中科院分区：
文献类型：
--
作者：
Brisbois EJ;Major TC;Goudie MJ;Bartlett RH;Meyerhoff ME;Handa H
包括体外循环（ECC）回路在内的血液接触器械可能会因血小板活化和血栓形成而出现并发症。一氧化氮（NO）释放聚合物的开发是利用低水平NO防止血小板活化/粘附的能力来改善血液相容性的一种方法。在这项研究中，一种新的溶剂溶胀法是用来加载与NO供体S-亚硝基-N-乙酰青霉胺（SNAP）的硅橡胶管壁。这种SNAP-硅橡胶管的NO通量约为10000。1 × 10 − 10 mol cm − 2 min − 1，模拟正常内皮细胞释放NO的范围，至少稳定4 h。通过扫描电子显微镜获得的膨胀前后的管材图像表明，这种膨胀方法对管材的表面性能几乎没有影响。SNAP加载硅橡胶和硅橡胶对照管用于制造ECC回路，并在家兔血栓形成模型中进行评价。血流4小时后，装载SNAP的硅橡胶回路能够将血小板计数保持在基线的64%（硅橡胶对照为12%）。还观察到促凝室内血栓形成程度降低67%。本研究证明了通过简单的溶剂溶胀-阻抗技术改善现有/市售硅橡胶管路血液相容性的能力，该技术也可适用于其他硅橡胶血液接触器械。将硅橡胶（SR）管浸泡在溶胀溶液中，用S-亚硝基-N-乙酰青霉胺（SNAP）包裹整个管壁。SNAP-硅橡胶管用于制造体外循环（ECC）回路，可输送一氧化氮（NO）（一种血小板粘附/活化的强效抑制剂），并可显著减少家兔血栓形成模型中的血栓形成。
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-impegnation technique, which may also be applicable to other silicone-based blood-contacting devices. 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.