The effect of gradually graded shear stress on the morphological integrity of a huvec-seeded compliant small-diameter vascular graft
The effect of gradually graded shear stress on the morphological integrity of a huvec-seeded compliant small-diameter vascular graft
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DOI：
10.1016/j.biomaterials.2006.09.020
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发表时间：
2007-01-01
期刊：
影响因子：
14
通讯作者：
Matsuda, Takehisa
中科院分区：
文献类型：
--
作者：
Inoguchi, Hiroyuki;Tanaka, Takashi;Matsuda, Takehisa
组织工程移植物的过早内皮化常常在植入动脉循环的早期引起细胞脱离，导致植入早期的闭塞。本研究的目的是确定体外施加的逐渐增加的剪切应力是否可以改善细胞保留和组织形态完整性，包括细胞形状和排列、肌动蛋白纤维排列和血管内皮 (VE) 钙粘蛋白的表达。用于本研究的组织工程移植物是人脐静脉内皮细胞（HUVEC）接种的顺应性小直径移植物，由通过静电纺丝制造的POLY（L-丙交酯-共-ε-己内酯）纤维网制成。使用定制设计的模拟循环装置产生的施加到移植物的剪切应力分别为 3.2、8.7 和 19.6 dyn/cm(2)。在剪切应力暴露之前完全单层的移植物表现出多边形鹅卵石形态，在相邻细胞的连续外围区域具有随机分布的肌动蛋白纤维和VE钙粘蛋白。相当于动脉循环系统的高剪切应力（8.7和19.6dyn/cm(2)）的24小时加载导致严重的细胞损伤，导致细胞完全丧失。然而，从低（3.2dyn/cm(2)）到高剪切应力（19.6dyn/cm(2)）逐渐增加的分级暴露导致细胞脱离显着减少，细胞形状高度拉长，细胞和肌动蛋白纤维的方向或排列（与流动方向平行）。尽管尚未检测到 VE-钙粘蛋白表达，但实现了更高程度的组织完整性，这可能会大大提高性能，特别是在植入早期。 (c) 2006 Elsevier Ltd. 保留所有权利。
The premature endothelialization of tissue-engineered grafts had often induced cellular detachment at an early period of implantation in arterial circulation, resulting in occlusion at an early period of implantation. This study was aimed to determine whether gradually increased shear stress applied ex vivo improves cell retention and tissue morphological integrity including cell shape and alignment, actin fiber alignment and expression of vascular endothelial (VE) cadherin. Tissue-engineered grafts used for this study were human umbilical vein endothelial cell (HUVEC)-seeded compliant small-diameter grafts made of POLY(L-lactide-co-epsilon-caprolactone) fiber meshes fabricated by electrospinning. The shear stresses applied to grafts, generated using a custom-designed mock circulatory apparatus, were 3.2, 8.7 and 19.6 dyn/cm(2). The grafts completely monolayered prior to shear stress exposure exhibited a polygonal cobblestone morphology with randomly distributed actin fibers and VE cadherin at the continuous peripheral region of adjacent cells. The 24-h-loading of high shear stresses (8.7 and 19.6dyn/cm(2)) equivalent to those of the arterial circulatory system resulted in severe cellular damage resulting in the complete loss of cells. However, a gradually increased graded exposure from a low (3.2dyn/cm(2)) to a high shear stress (19.6dyn/cm(2)) resulted in a markedly reduced cell detachment, a highly elongated cell shape, and orientation or alignment of both cells and actin fibers, which were parallel to the direction of flow. Although VE-cadherin expression was not detected yet, a higher degree of tissue integrity was achieved, which may greatly improve the performance particularly at an early period of implantation. (c) 2006 Elsevier Ltd. All rights reserved.