In Vitro Model of a Fibrosa Layer of a Heart Valve
In Vitro Model of a Fibrosa Layer of a Heart Valve
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DOI：
10.1021/acsami.5b04805
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发表时间：
2015-09-16
影响因子：
9.5
通讯作者：
Simarit, Robert D.
中科院分区：
文献类型：
--
作者：
Jana, Soumen;Lerman, Amir;Simarit, Robert D.
心脏主动脉瓣的纤维层主要由沿圆周方向取向的I型胶原纤维的致密网络组成。该主层承受拉伸载荷并响应小叶上的高应力。内纤维层也是导致瓣膜功能障碍（包括狭窄和返流）的病理生理变化的部位。这些变化的体外研究受到缺乏模拟纤维层周向结构的基质的限制。在心脏瓣膜组织工程中，该层的生成是具有挑战性的。本研究旨在开发天然主动脉瓣叶的人工纤维层。一个独特的形态仿生，柔韧，但独立的基板与周向取向的纳米纤维，通过静电纺丝上的一种新的收集器设计用于这项研究。基质具有低体积拉伸刚度和极限强度;因此，培养的瓣膜间质细胞（VIC）显示出通常在健康主动脉瓣叶中观察到的成纤维细胞表型。此外，基质中VIC的基因和蛋白质表达及形态接近天然主动脉瓣叶纤维层中的VIC。这种人工纤维层可用于瓣膜功能障碍的体外研究。
The fibrosa layer of a cardiac aortic valve is composed mostly of a dense network of type I collagen fibers oriented in circumferential direction. This main layer bears the tensile load and responds to the high stress on a leaflet. The inner fibrosa layer is also the site of pathophysiologic changes that result in valvular dysfunction, including stenosis and regurgitation. In vitro studies of these changes are limited by the absence of a substrate that mimics the circumferentially oriented structure of the fibrosa layer. In heart valve tissue engineering, generation of this layer is challenging. This study aimed to develop an artificial fibrosa layer of a native aortic leaflet. A unique morphologically biomimicked, pliable, but standalone substrate with circumferentially oriented nanofibers was fabricated by electrospinning on a novel collector designed for this study. The substrate had low-bulk tensile stiffness and ultimate strength; thus, cultured valvular interstitial cells (VICs) showed a fibroblast phenotype that is generally observed in a healthy aortic leaflet. Furthermore, gene and protein expression and morphology of VICs in substrates were close to those in the fibrosa layer of a native aortic leaflet. This artificial fibrosa layer can be useful for in vitro studies of valvular dysfunctions.