Rare earth metals used in biodegradable magnesium-based stents do not interfere with proliferation of smooth muscle cells but do induce the upregulation of inflammatory genes

Rare earth metals used in biodegradable magnesium-based stents do not interfere with proliferation of smooth muscle cells but do induce the upregulation of inflammatory genes
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DOI:
10.1002/jbm.a.32235
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发表时间:
2009-11-01
影响因子:
4.9
通讯作者:
Peuster, Matthias
Peuster, Matthias
中科院分区:
工程技术3区
文献类型:
--
作者:
Drynda, Andreas;Deinet, Nicole;Peuster, Matthias

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稀土金属以少量(最多 10%)添加到易腐蚀的镁基合金中,以提高其机械性能并降低降解率。铈 (Ce)、钕 (Nd)、钇 (Y) 和镱 (Yb) 已用于可降解心血管支架。关于植入物降解过程中释放的稀土金属的生物相容性知之甚少。因此,根据人血管平滑肌细胞(SMC)的代谢活性评估稀土金属的生物相容性。与稀土金属三价氯化物 (0.5-100 μg/mL) 共孵育 24、72、144 和 240 小时后,使用比色 WST-1 测试测定每个时间点的代谢活性。所测试的稀土金属在很宽的浓度范围内不会导致代谢活性发生显着变化。然而,在高浓度下观察到下降。没有观察到细胞凋亡或坏死效应。此外,我们分析了 Ce、Nd、Y 和 Yb 对炎症过程相关基因表达的影响。使用定量实时PCR测量暴露于Ce、Nd、Y和Yb(5和50μg/mL)后SMC中IL-6、IL-8和ICAM-1的表达。 24小时后才发现IL-6、IL-8和ICAM-1基因显着上调,主要是在50μg/mL浓度下。我们的细胞培养数据表明稀土金属影响血管细胞的细胞过程。体内是否也会出现不良反应是进一步研究的主题。 (C) 2008 Wiley periodicals, Inc. J Biomed Mater Res 91 A: 360-369, 2009
Rare earth metals are added to corrodible magnesium-based alloys in low amounts (up to 10%) to improve their mechanical properties and to decrease the degradation rate. Cerium (Ce), neodymium (Nd), yttrium (Y), and ytterbium (Yb) are already used for degradable cardiovascular stents. Little is known about the biocompatibility of rare earth metals released during the degradation process of the implant. Therefore the biocompatibility of rare earth metals was assessed with regard to metabolic activity of human vascular smooth muscle cells (SMCs). After coincubation with the trivalent chlorides (0.5-100 mu g/mL) of rare earth metals for 24, 72, 144, and 240 h metabolic activity was determined at each time point using the colometric WST-1 test. The tested rare earth metals did not lead to significant changes in metabolic activity over a wide concentration range. However, at high concentrations a decrease was observed. Apoptotic or necrotic effects were not observed. Furthermore, we analyzed the effects of Ce, Nd, Y, and Yb on the expression of genes involved in inflammatory processes. The expression of IL-6, IL-8, and ICAM-1 in SMCs after exposure to Ce, Nd, Y, and Yb (5 and 50 mu g/mL) was measured using quantitative real-time PCR. Significant up-regulation of IL-6, IL-8, and ICAM-1 genes were only found after 24 h, mainly for a concentration of 50 mu g/mL. Our cell culture data indicate that rare earth metals influence cellular processes of vascular cells. Whether adverse effects occur also in in vivo is the topic of further investigations. (C) 2008 Wiley Periodicals, Inc. J Biomed Mater Res 91 A: 360-369, 2009