Department of Chemistry and ‡School of Biomedical Engineering, Colorado State University , 1872 Campus Delivery, Fort Collins, Colorado 80523, United States.
ACS Appl Mater Interfaces. 2013 Oct 9;5(19):9285-94. doi: 10.1021/am402112y. Epub 2013 Aug 19.
Tygon is a proprietary plasticized poly(vinyl chloride) polymer that is used widely in bioapplications, specifically as extracorporeal circuits. To overcome issues with blood clot formation and infection associated with the failure of these medical devices upon blood contact, we consider a Tygon coating with the ability to release the natural anticlotting and antibiotic agent, nitric oxide (NO), under simulated physiological conditions. These coatings are prepared by incorporating 20 w/w% S-nitrosoglutathione (GSNO) donor into a Tygon matrix. These films release NO on the order of 0.64 ± 0.5 × 10(-10) mol NO cm(-2) min(-1), which mimics the lower end of natural endothelium NO flux. We use a combination of assays to quantify the amount of GSNO that is found intact at different time points throughout the film soak, as well as monitor the total thiol content in the soaking solution due to any analyte that has leached from the polymer film. We find that a burst of GSNO is released from the material surface within 5 min to 1 h of soaking, which only represents 0.25% of the total GSNO contained in the film. After 1 h of film soak, no additional GSNO is detected in the soaking solution. By further considering the total thiol content in solution relative to the intact GSNO, we demonstrate that the amount of GSNO leached from the material into the buffer soaking solution does not contribute significantly to the total NO released from the GSNO-incorporated Tygon film (<10% total NO). Further surface analysis using SEM-EDS traces the elemental S on the material surface, demonstrating that within 5 min -1 h soaking time, 90% of the surface S is removed from the material. Surface wettability and roughness measurements indicate no changes between the GSNO-incorporated films pre- to postsoak that will be significant toward the adsorption of biological components, such as proteins, relative to the presoaked donor-incorporated film. Overall, we demonstrate that, for a 20 w/w% GSNO-incorporated Tygon film, relatively minimal GSNO leaching is experienced, and the lost GSNO is from the material surface. Varying the donor concentration from 5 to 30 w/w% GSNO within the film does not result in significantly different NO release profiles. Additionally, the steady NO flux associated with the system is predominantly due to localized release from the material, and not donor lost to soaking solution. The surface properties of these materials generally imply that they are useful for blood-contacting applications.
特氟龙是一种专有的增塑聚氯乙烯聚合物,广泛应用于生物应用中,特别是作为体外循环。为了克服这些医疗器械在与血液接触时因血液凝固和感染而失效的问题,我们考虑在特氟龙涂层中释放天然抗凝血和抗生素药物一氧化氮(NO),在模拟生理条件下。这些涂层是通过将 20 w/w% 的 S-亚硝基谷胱甘肽(GSNO)供体掺入特氟龙基质中来制备的。这些薄膜在 0.64 ± 0.5×10(-10) mol NO cm(-2) min(-1)的量级上释放 NO,这模拟了天然内皮细胞 NO 通量的低端。我们使用一系列测定法来量化在整个膜浸泡过程中不同时间点完整存在的 GSNO 的量,以及监测由于从聚合物膜中浸出的任何分析物而导致的浸泡溶液中的总巯基含量。我们发现,在浸泡的 5 分钟到 1 小时内,材料表面会释放出大量的 GSNO,这仅占膜中总 GSNO 的 0.25%。浸泡 1 小时后,浸泡溶液中未检测到额外的 GSNO。通过进一步考虑溶液中总巯基含量与完整 GSNO 的关系,我们证明从材料中浸出到缓冲液浸泡溶液中的 GSNO 量不会显著增加从掺入 GSNO 的特氟龙膜释放的总 NO(<10%的总 NO)。进一步使用 SEM-EDS 对材料表面的元素 S 进行表面分析,证明在 5 分钟到 1 小时的浸泡时间内,90%的表面 S 从材料中去除。表面润湿性和粗糙度测量表明,在浸泡前后,掺入 GSNO 的薄膜的表面特性没有明显变化,与预浸泡供体掺入的薄膜相比,这将对生物成分(如蛋白质)的吸附没有显著影响。总的来说,我们证明对于 20 w/w% GSNO 掺入的特氟龙膜,经历了相对较少的 GSNO 浸出,并且丢失的 GSNO 来自材料表面。在膜内将供体浓度从 5 到 30 w/w% GSNO 变化不会导致明显不同的 NO 释放曲线。此外,与该系统相关的稳定 NO 通量主要是由于材料的局部释放,而不是供体浸出到浸泡溶液中。这些材料的表面特性通常意味着它们可用于与血液接触的应用。