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新型支架表面材料:聚合物依赖的人内皮细胞、平滑肌细胞和血小板相互作用的影响

New stent surface materials: the impact of polymer-dependent interactions of human endothelial cells, smooth muscle cells, and platelets.

作者信息

Busch Raila, Strohbach Anne, Rethfeldt Stefanie, Walz Simon, Busch Mathias, Petersen Svea, Felix Stephan, Sternberg Katrin

机构信息

University of Greifswald, Clinic for Internal Medicine B, Sauerbruchstraße, D-17475 Greifswald, Germany.

University of Greifswald, Clinic for Internal Medicine B, Sauerbruchstraße, D-17475 Greifswald, Germany.

出版信息

Acta Biomater. 2014 Feb;10(2):688-700. doi: 10.1016/j.actbio.2013.10.015. Epub 2013 Oct 19.

Abstract

Despite the development of new coronary stent technologies, in-stent restenosis and stent thrombosis are still clinically relevant. Interactions of blood and tissue cells with the implanted material may represent an important cause of these side effects. We hypothesize material-dependent interaction of blood and tissue cells. The aim of this study is accordingly to investigate the impact of vascular endothelial cells, smooth muscle cells and platelets with various biodegradable polymers to identify a stent coating or platform material that demonstrates excellent endothelial-cell-supportive and non-thrombogenic properties. Human umbilical venous endothelial cells, human coronary arterial endothelial cells and human coronary arterial smooth muscle cells were cultivated on the surfaces of two established biostable polymers used for drug-eluting stents, namely poly(ethylene-co-vinylacetate) (PEVA) and poly(butyl methacrylate) (PBMA). We compared these polymers to new biodegradable polyesters poly(l-lactide) (PLLA), poly(3-hydroxybutyrate) (P(3HB)), poly(4-hydroxybutyrate) (P(4HB)) and a polymeric blend of PLLA/P(4HB) in a ratio of 78/22% (w/w). Biocompatibility tests were performed under static and dynamic conditions. Measurement of cell proliferation, viability, glycocalix width, eNOS and PECAM-1 mRNA expression revealed strong material dependency among the six polymer samples investigated. Only the polymeric blend of PLLA/P(4HB) achieved excellent endothelial markers of biocompatibility. Data show that PLLA and P(4HB) tend to a more thrombotic response, whereas the polymer blend is characterized by a lower thrombotic potential. These data demonstrate material-dependent endothelialization, smooth muscle cell growth and thrombogenicity. Although polymers such as PEVA and PBMA are already commonly used for vascular implants, they did not sufficiently meet the criteria for biocompatibility. The investigated biodegradable polymeric blend PLLA/P(4HB) evidently represents a promising material for vascular stents and stent coatings.

摘要

尽管新型冠状动脉支架技术不断发展,但支架内再狭窄和支架血栓形成在临床上仍然具有重要意义。血液和组织细胞与植入材料的相互作用可能是这些副作用的一个重要原因。我们推测血液和组织细胞与材料的相互作用存在材料依赖性。因此,本研究的目的是研究血管内皮细胞、平滑肌细胞和血小板与各种可生物降解聚合物的相互作用,以确定一种具有优异内皮细胞支持和抗血栓形成特性的支架涂层或平台材料。将人脐静脉内皮细胞、人冠状动脉内皮细胞和人冠状动脉平滑肌细胞培养在两种用于药物洗脱支架的已确立的生物稳定聚合物表面,即聚(乙烯 - 共 - 醋酸乙烯酯)(PEVA)和聚(甲基丙烯酸丁酯)(PBMA)。我们将这些聚合物与新型可生物降解聚酯聚(L - 丙交酯)(PLLA)、聚(3 - 羟基丁酸酯)(P(3HB))、聚(4 - 羟基丁酸酯)(P(4HB))以及比例为78/22%(w/w)的PLLA/P(4HB)聚合物共混物进行比较。在静态和动态条件下进行生物相容性测试。细胞增殖、活力、糖萼宽度、eNOS和PECAM - 1 mRNA表达的测量结果显示,在所研究的六种聚合物样品中存在强烈的材料依赖性。只有PLLA/P(4HB)聚合物共混物达到了优异的生物相容性内皮标记物。数据表明,PLLA和P(4HB)倾向于产生更强的血栓形成反应,而该聚合物共混物的特点是血栓形成潜力较低。这些数据证明了材料依赖性的内皮化、平滑肌细胞生长和血栓形成性。尽管诸如PEVA和PBMA等聚合物已普遍用于血管植入物,但它们并不完全符合生物相容性标准。所研究的可生物降解聚合物共混物PLLA/P(4HB)显然是一种有前途的血管支架和支架涂层材料。

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