Arterial graft with elastic layer structure grown from cells.
Arterial graft with elastic layer structure grown from cells.
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DOI：
10.1038/s41598-017-00237-1
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发表时间：
2017-03-10
影响因子：
4.6
通讯作者：
Ishikawa Y
中科院分区：
文献类型：
--
作者：
Yokoyama U;Tonooka Y;Koretake R;Akimoto T;Gonda Y;Saito J;Umemura M;Fujita T;Sakuma S;Arai F;Kaneko M;Ishikawa Y
由于自体血管来源的不足和人工血管的缺点，人们对组织工程血管移植的发展越来越感兴趣。然而，由层状弹性层组成的中膜在很大程度上决定了动脉的弹性，并且很难合成。在这里，我们描述了一种从培养的人血管SMCs中制造具有弹性层结构的动脉移植物的方法，该方法通过在重复细胞播种期间周期性暴露于极高的静水压力（HP）中。在110和180 kPa之间重复的慢循环（0.002 Hz）增加了应力纤维聚合和纤维连接蛋白在SMCs上的纤维形成，这是弹性纤维形成所必需的。为了制造动脉移植物，大鼠血管SMCs播种和周期性HP暴露交替重复10次。获得的内侧移植物具有高弹性，抗拉断裂强度为1451±159 mmHg，弹性纤维丰富。在大鼠主动脉处缝合内侧贴片，在2.5个月后发现完全通畅并内皮化，尽管作为主动脉间置移植物植入大鼠的管状内侧构建物仅在急性早期耐受动脉血压。这种新颖的有组织的自组装方法将使体外无支架动脉移植物的大规模生产成为可能，并具有潜在的治疗心血管疾病的应用。
Shortage of autologous blood vessel sources and disadvantages of synthetic grafts have increased interest in the development of tissue-engineered vascular grafts. However, tunica media, which comprises layered elastic laminae, largely determines arterial elasticity, and is difficult to synthesize. Here, we describe a method for fabrication of arterial grafts with elastic layer structure from cultured human vascular SMCs by periodic exposure to extremely high hydrostatic pressure (HP) during repeated cell seeding. Repeated slow cycles (0.002 Hz) between 110 and 180 kPa increased stress-fiber polymerization and fibronectin fibrillogenesis on SMCs, which is required for elastic fiber formation. To fabricate arterial grafts, seeding of rat vascular SMCs and exposure to the periodic HP were repeated alternatively ten times. The obtained medial grafts were highly elastic and tensile rupture strength was 1451 ± 159 mmHg, in which elastic fibers were abundantly formed. The patch medial grafts were sutured at the rat aorta and found to be completely patent and endothelialized after 2.5 months, although tubular medial constructs implanted in rats as interpositional aortic grafts withstood arterial blood pressure only in early acute phase. This novel organized self-assembly method would enable mass production of scaffold-free arterial grafts in vitro and have potential therapeutic applications for cardiovascular diseases.