• 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Acta biomaterialia >Copper nanoparticle cues for biomimetic cellular assembly of crosslinked elastin fibers.
【24h】

Copper nanoparticle cues for biomimetic cellular assembly of crosslinked elastin fibers.

机译：铜纳米粒子线索，用于交联弹性蛋白纤维的仿生细胞组装。

获取原文
获取原文并翻译 | 示例
           
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

Elastin, a structural protein distributed in the extracellular matrix of vascular tissues, is critical to maintaining the elastic stability and mechanical properties of blood vessels, as well as regulating cell-signaling pathways involved in vascular injury response and morphogenesis. Pathological degradation of vascular elastin or its malformation within native vessels and the poor ability to tissue-engineer elastin-rich vascular replacements due to innately poor elastin synthesis by adult vascular cells can compromise vascular homeostasis, and must thus be addressed. Our recent studies attest to the utility of hyaluronan (HA) oligomers for elastin synthesis and organization by adult vascular smooth muscle cells (SMCs), though the elastin matrix yields in these cases were quite low relative to total elastin produced. Thus, in this study, we investigated the utility of copper (Cu(2+)) ions to enhance cellular elastin deposition, crosslinking and maturation into structural fibers. Copper nanoparticles (CuNPs; 80-100 nm) in the dose range of 1-100 ng ml(-1) were tested for Cu(2+) ion release, and based on mathematical modeling of their release profiles, CuNPs (1, 10, and 400 ng ml(-1)) were chosen for supplementation to adult SMC cultures. The 400 ng ml(-1) dose of CuNPs cumulatively delivered Cu(2+) doses in the range of 0.1 M, over the 21 day culture period. It was observed that while exogenous CuNP supplements do not up-regulate tropoelastin production by vascular SMCs, they promoted formation of crosslinked elastin matrices. The deposition of crosslinked matrix elastin was further improved by the additional presence of HA oligomers in these cultures. Immunofluorescence imaging and structural analysis of the isolated elastin matrices indicate that amorphous elastin clumps were formed within non-additive control cultures, while aggregating elastin fibrils were observed within SMC cultures treated with CuNPs (1-10 ng ml(-1)) alone or together with HA oligomers. The presence of 400 ng ml(-1) of CuNPs concurrent with HA oligomers furthered aggregation of these elastin fibrils into mature fibers with diameters ranging from 200 to 500 nm. Ultrastructural analysis of elastin matrix within cultures treated with HA oligomers and 400 ng ml(-1) of CuNPs suggest that elastin matrix deposition as stimulated by Cu(2+) ions proceeds via a fibrillin-mediated assembly process, with enhanced crosslinking occurring via stimulation of lysyl oxidase. Overall, the data suggest that CuNPs and HA oligomers are highly useful for regenerating crosslinked, fibrillar elastin matrices by adult vascular SMCs. These results have immense utility in tissue-engineering vascular replacements.
机译：弹性蛋白是一种分布在血管组织细胞外基质中的结构蛋白，对于维持血管的弹性稳定性和机械性能以及调节参与血管损伤反应和形态发生的细胞信号通路至关重要。血管弹性蛋白的病理降解或其在天然血管中的畸形，以及由于成年血管细胞固有的弹性蛋白合成差而导致的组织工程化富含弹性蛋白的血管替代物的能力差，会损害血管的稳态，因此必须加以解决。我们的最新研究证明，透明质酸（HA）低聚物可通过成年血管平滑肌细胞（SMC）合成弹性蛋白并进行组织，尽管在这些情况下，弹性蛋白基质的产量相对于生产的总弹性蛋白而言相当低。因此，在这项研究中，我们调查了铜（Cu（2+））离子增强细胞弹性蛋白沉积，交联和成熟成结构纤维的效用。铜纳米颗粒（CuNPs; 80-100 nm）在1-100 ng ml（-1）的剂量范围内进行了Cu（2+）离子释放测试，并基于其释放曲线的数学模型CuNPs（1，10 ，并选择400 ng ml（-1））作为成人SMC培养液的补充。在21天的培养期间，400 ng ml（-1）剂量的CuNPs累积递送的Cu（2+）剂量为0.1M。观察到，虽然外源性CuNP补充剂不会上调血管SMC产生的原弹性蛋白，但它们会促进交联弹性蛋白基质的形成。这些培养物中还存在HA低聚物，从而进一步改善了交联基质弹性蛋白的沉积。免疫荧光成像和分离的弹性蛋白基质的结构分析表明，在非添加性对照培养物中形成了无定形弹性蛋白团块，而在单独或一起使用CuNPs（1-10 ng ml（-1））处理的SMC培养物中观察到了聚集的弹性蛋白原纤维。 HA低聚物。 400 ng ml（-1）的CuNPs与HA低聚物同时存在进一步促进了这些弹性蛋白原纤维的聚集，形成直径为200至500 nm的成熟纤维。用HA低聚物和400 ng ml（-1）的CuNPs处理的培养物中弹力蛋白基质的超微结构分析表明，被原纤维蛋白介导的组装过程通过Cu（2+）离子刺激而产生的弹性蛋白基质沉积，通过刺激发生交联赖氨酰氧化酶。总体而言，数据表明CuNP和HA低聚物对于成人血管SMC再生交联的原纤维弹性蛋白基质非常有用。这些结果在组织工程血管替代中具有巨大的用途。

著录项

相似文献

  • 外文文献
  • 中文文献
  • 专利
获取原文

客服邮箱：kefu@zhangqiaokeyan.com

京公网安备：11010802029741号 ICP备案号：京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有

  • 客服微信

  • 服务号