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颅内血流导向装置的纤维蛋白基、止血模拟纳米涂层的体外研究。

In vitro investigation of an intracranial flow diverter with a fibrin-based, hemostasis mimicking, nanocoating.

机构信息

Department of Thoracic, Cardiac and Vascular Surgery, University Hospital Tuebingen, Tuebingen, Germany.

Section Medical Materials Science & Technology, University Hospital Tuebingen, Tuebingen, Germany.

出版信息

Biomed Mater. 2020 Dec 17;16(1):015026. doi: 10.1088/1748-605X/abc8d3.

Abstract

Flow diversion aims at treatment of intracranial aneurysms via vessel remodeling mechanisms, avoiding the implantation of foreign materials into the aneurysm sack. However, complex implantation procedure, high metal surface and hemodynamic disturbance still pose a risk for thromboembolic complications in the clinical praxis. A novel fibrin and heparin based nano coating considered as a hemocompatible scaffold for neointimal formation was investigated regarding thrombogenicity and endothelialization. The fibrin-heparin coating was compared to a bare metal as well as fibrin- or heparin-coated flow diverters. The implants were tested separately in regard to inflammation and coagulation markers in two different in vitro hemocompatibility models conducted with human whole blood (n = 5). Endothelialization was investigated through a novel dynamic in vitro cell seeding model containing primary human cells with subsequent viability assay. It was demonstrated that platelet loss and platelet activation triggered by presence of a bare metal stent could be significantly reduced by applying the fibrin-heparin, fibrin and heparin coating. Viability of endothelial cells after proliferation was similar in fibrin-heparin compared to bare metal implants, with a slight, non-significant improvement observed in the fibrin-heparin group. The results suggest that the presented nanocoating has the potential to reduce thromboembolic complications in a clinical setting. Though the new model allowed for endothelial cell proliferation under flow conditions, a higher number of samples is required to assess a possible effect of the coating.

摘要

血流导向装置通过血管重塑机制治疗颅内动脉瘤,避免将异物植入动脉瘤囊中。然而,在临床实践中,复杂的植入程序、高金属表面和血液动力学干扰仍然存在血栓栓塞并发症的风险。一种新型的纤维蛋白和肝素基纳米涂层被认为是一种有利于新生内膜形成的抗血栓性支架,研究了其血栓形成和内皮化特性。将纤维蛋白-肝素涂层与裸金属以及纤维蛋白或肝素涂层的血流导向装置进行了比较。在两个不同的体外血液相容性模型中(n=5),用人全血分别测试了植入物的炎症和凝血标志物。通过含有原代人细胞的新型动态体外细胞接种模型研究了内皮化,随后进行了活力测定。结果表明,通过应用纤维蛋白-肝素、纤维蛋白和肝素涂层,可以显著减少裸金属支架引起的血小板丢失和血小板激活。纤维蛋白-肝素涂层与裸金属植入物相比,内皮细胞增殖后的活力相似,在纤维蛋白-肝素组观察到略有但无统计学意义的改善。研究结果表明,所提出的纳米涂层具有减少临床血栓栓塞并发症的潜力。虽然新模型允许在流动条件下进行内皮细胞增殖,但需要更多的样本来评估涂层的可能效果。

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