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用于心脏瓣膜组织工程的海藻酸钠水凝胶支架的生物制造。

Biofabrication of Sodium Alginate Hydrogel Scaffolds for Heart Valve Tissue Engineering.

机构信息

Department of Mechanical Engineering, Faculty of Science and Engineering, Université Laval, 1065 Avenue de la Médecine, Quebec City, QC G1V 0A6, Canada.

Centre de Recherche en Organogénèse Expérimentale de l'Université Laval/LOEX, Centre de Recherche du CHU de Québec-Université Laval, 1401, 18e rue, Quebec City, QC G1J 1Z4, Canada.

出版信息

Int J Mol Sci. 2022 Aug 2;23(15):8567. doi: 10.3390/ijms23158567.

Abstract

Every year, thousands of aortic valve replacements must take place due to valve diseases. Tissue-engineered heart valves represent promising valve substitutes with remodeling, regeneration, and growth capabilities. However, the accurate reproduction of the complex three-dimensional (3D) anatomy of the aortic valve remains a challenge for current biofabrication methods. We present a novel technique for rapid fabrication of native-like tricuspid aortic valve scaffolds made of an alginate-based hydrogel. Using this technique, a sodium alginate hydrogel formulation is injected into a mold produced using a custom-made sugar glass 3D printer. The mold is then dissolved using a custom-made dissolving module, revealing the aortic valve scaffold. To assess the reproducibility of the technique, three scaffolds were thoroughly compared. CT (computed tomography) scans showed that the scaffolds respect the complex native geometry with minimal variations. The scaffolds were then tested in a cardiac bioreactor specially designed to reproduce physiological flow and pressure (aortic and ventricular) conditions. The flow and pressure profiles were similar to the physiological ones for the three valve scaffolds, with small variabilities. These early results establish the functional repeatability of this new biofabrication method and suggest its application for rapid fabrication of ready-to-use cell-seeded sodium alginate scaffolds for heart valve tissue engineering.

摘要

每年,由于瓣膜疾病,都有数千例主动脉瓣置换术需要进行。组织工程心脏瓣膜具有重塑、再生和生长的能力,是很有前途的瓣膜替代物。然而,当前的生物制造方法仍然难以准确复制主动脉瓣的复杂三维(3D)解剖结构。我们提出了一种使用基于藻酸盐的水凝胶快速制造类似于天然三叶式主动脉瓣支架的新方法。使用这种技术,将藻酸钠水凝胶制剂注入使用定制的糖玻璃 3D 打印机制作的模具中。然后使用定制的溶解模块溶解模具,露出主动脉瓣支架。为了评估该技术的可重复性,我们对三个支架进行了彻底的比较。CT(计算机断层扫描)扫描显示,支架以最小的变化尊重复杂的天然几何形状。然后,将支架在专门设计的心脏生物反应器中进行测试,该生物反应器专门用于复制生理流动和压力(主动脉和心室)条件。三个瓣膜支架的流动和压力曲线与生理曲线相似,具有较小的可变性。这些早期结果确立了这种新生物制造方法的功能可重复性,并表明其适用于快速制造可用于心脏瓣膜组织工程的即用型细胞接种的藻酸钠支架。

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