A tissue-engineered heart valve can be an alternative to a prosthetic valve in heart valve replacement; however, it is not fully efficient in terms of long-lasting functionality, as leaflets in engineered valves do not possess the trilayered native leaflet structure. Previously, we developed a flat, trilayered, oriented nanofibrous (TN) scaffold mimicking the trilayered structure and orientation of native heart valve leaflets. In vivo tissue engineering—a practical regenerative medicine technology—can be used to develop an autologous heart valve. Thus, in this study, we used our flat, trilayered, oriented nanofibrous scaffolds to develop trilayered tissue structures with native leaflet orientations through in vivo tissue engineering in a rat model. After 2 months of in vivo tissue engineering, infiltrated cells and their deposited collagen fibrils were found aligned in the circumferential and radial layers, and randomly oriented in the random layer of the scaffolds, i.e., trilayered tissue constructs (TTCs) were developed. Tensile properties of the TTCs were higher than that of the control tissue constructs (without any scaffolds) due to influence of fibers of the scaffolds in tissue engineering. Different extracellular matrix proteins—collagen, glycosaminoglycans, and elastin—that exist in native leaflets were observed in the TTCs. Gene expression of the TTCs indicated that the tissue constructs were in growing stage. There was no sign of calcification in the tissue constructs. The TTCs developed with the flat TN scaffolds indicate that an autologous leaflet-shaped, trilayered tissue construct that can function as a native leaflet can be developed.

中文翻译：

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模仿三层天然心脏瓣膜小叶方向的三层组织结构

在心脏瓣膜置换术中，组织工程心脏瓣膜可以替代人工瓣膜；然而，就持久功能而言，它并不完全有效，因为工程瓣膜中的小叶不具有三层天然小叶结构。以前，我们开发了一种扁平的、三层的、定向的纳米纤维 (TN) 支架，模仿天然心脏瓣膜小叶的三层结构和方向。体内组织工程——一种实用的再生医学技术——可用于开发自体心脏瓣膜。因此，在这项研究中，我们使用扁平的、三层的、定向的纳米纤维支架通过大鼠模型的体内组织工程开发具有天然小叶方向的三层组织结构。经过2个月的体内组织工程，发现浸润细胞及其沉积的胶原原纤维排列在圆周层和径向层中，并且在支架的随机层中随机定向，即开发了三层组织结构（TTC）。由于组织工程中支架纤维的影响，TTC 的拉伸性能高于对照组织结构（没有任何支架）。在 TTC 中观察到存在于天然小叶中的不同细胞外基质蛋白——胶原蛋白、糖胺聚糖和弹性蛋白。TTCs的基因表达表明组织构建体处于生长阶段。在组织结构中没有钙化的迹象。用扁平 TN 支架开发的 TTC 表明自体小叶形，