Ketchum Alex R, Kappler Michael P, Wu Jianfeng, Xi Chuanwu, Meyerhoff Mark E
Department of Chemistry, University of Michigan, Ann Arbor, MI 48109.
Department of Environmental Health Sciences, University of Michigan School of Public Health, Ann Arbor, MI 48109.
J Mater Chem B. 2016 Jan 21;4(3):422-430. doi: 10.1039/C5TB01664A. Epub 2015 Dec 7.
Recently, considerable research efforts have focused on increasing the biocompatibility a nd bactericidal activity of biomedical polymeric devices (e.g., catheters, etc.) through incorporation of nitric oxide (NO) releasing molecules. NO is an important endogenous molecule that is well known for enhancing blood flow via its vasodilatory activity, but it also exhibits potent antithrombotic and antimicrobial properties. In this work, we demonstrate that silicone rubber tubing can be impregnated with a tertiary -nitrosothiol (RSNO), -nitroso--dodecylmercaptan, via a simple solvent swelling method. We further characterize the NO release and RSNO leaching from the tubing over time via use of chemiluminescence and UV/Vis spectroscopy, respectively. The tubing is shown to maintain an NO flux above the physiological levels released by endothelial cells, 0.5-4.0 × 10 molcmmin, for more than 3 weeks while stored at 37 °C and exhibit minimal leaching. Finally, the RSNO impregnated tu bing exhibits significant antimicrobial activity over a 21 d period (vs. controls) during incubation in a CDC bioreactor after inoculation of media with bacteria. The use of such lipophilic RSNO impregnated silicone rubber tubing could dramatically reduce the risk of catheter-related infections, which are a common problem associated with placement of intravascular or urinary catheters.
最近,大量的研究工作集中在通过掺入释放一氧化氮(NO)的分子来提高生物医学聚合物装置(如导管等)的生物相容性和杀菌活性。NO是一种重要的内源性分子,以其血管舒张活性增强血流而闻名,但它也具有强大的抗血栓和抗菌特性。在这项工作中,我们证明了硅橡胶管可以通过简单的溶剂溶胀法用叔亚硝基硫醇(RSNO),即亚硝基十二烷基硫醇进行浸渍。我们分别通过化学发光和紫外/可见光谱法进一步表征了随着时间推移从管中释放的NO和RSNO的浸出情况。结果表明,该管在37°C储存时,能在超过3周的时间内保持高于内皮细胞释放的生理水平(0.5 - 4.0×10⁻⁸ mol·cm⁻²·min⁻¹)的NO通量,并且浸出量极小。最后,在用细菌接种培养基后,在CDC生物反应器中孵育的21天期间,浸有RSNO的管表现出显著的抗菌活性(与对照相比)。使用这种浸有亲脂性RSNO的硅橡胶管可以显著降低与导管相关的感染风险,这是血管内或导尿管放置常见的问题。