Centre for Nanotechnology & Regenerative Medicine, University College London, London, UK.
J Mater Sci Mater Med. 2014 Mar;25(3):917-29. doi: 10.1007/s10856-013-5103-2. Epub 2013 Nov 30.
Cardiovascular implants must resist thrombosis and intimal hyperplasia, but they are prone to such patency limiting conditions during graft implantation and prior to endothelialisation. Nitric oxide (NO) released from the endothelium has a complex protective role in the cardiovascular system, and this study has addressed: (1) in situ NO release profiles from S-nitrosothiols ((S-Nitroso-N-acetylpenicillamine (SNAP) and (S-Nitrosoglutathione (GSNO)) incorporated into polyhedral oligomeric silsesquioxanepoly(carbonate-urea)urethane (POSS-PCU) coronary artery bypass grafts (CABG) in a physiological pulsatile flow, and (2) the determination of their interaction with endothelial progenitor cells (EPCs), smooth muscle cells, platelets, whole blood kinetics. It was found that 1, 2, and 3 wt% SNAP/GSNO incorporated into POSS-PCU-CABG successfully eluted NO, but optimal elution was evident with 2 %-SNAP-POSS-PCU. NO release determined under static conditions using the Griess assay, and in situ measurements under pulsatile flow using amperometric probe was found to differ, thus confirming the significance of monitoring NO-elution under haemodynamic conditions. 2 %-SNAP-POSS-PCU demonstrated anti-thrombogenic kinetics through thromboelastography measurements, while metabolic activity using Alamar Blue™ assay and scanning electron microscopy demonstrated greater adhesion of EPCs and reduced adhesion of platelets.
心血管植入物必须抵抗血栓形成和内膜增生,但在移植物植入和内皮化之前,它们容易出现这种导致血管通畅受限的情况。一氧化氮 (NO) 从内皮释放,在心血管系统中具有复杂的保护作用,本研究解决了以下问题:(1)将 S-亚硝基硫醇((S-亚硝基-N-乙酰青霉胺 (SNAP) 和(S-亚硝基谷胱甘肽 (GSNO)) 掺入多面体低聚倍半硅氧烷聚(碳酸酯-脲)聚氨酯(POSS-PCU)冠状动脉旁路移植术 (CABG) 在生理脉动流中的原位 NO 释放曲线,以及(2)确定它们与内皮祖细胞 (EPC)、平滑肌细胞、血小板、全血动力学的相互作用。结果发现,1、2 和 3 wt% 的 SNAP/GSNO 掺入 POSS-PCU-CABG 中成功洗脱了 NO,但 2%-SNAP-POSS-PCU 显示出最佳洗脱效果。使用格里塞斯测定法在静态条件下确定的 NO 释放和在脉动流条件下使用安培探针进行的原位测量结果不同,这证实了在血液动力学条件下监测 NO 洗脱的重要性。2%-SNAP-POSS-PCU 通过血栓弹性图测量显示出抗血栓形成动力学,而使用 Alamar Blue™ 测定法和扫描电子显微镜测量的代谢活性表明 EPC 的黏附性增加,血小板的黏附性降低。