Stretchable Hydrogel Bioinks-Enabled Microfluidic Bioprinting of Functional Small-Diameter Blood Vessels

摘要 血管在循环系统中起着至关重要的作用。血管的主要功能是运输 血液从心脏流向全身的其他组织和器官，然后带回 心。血管的结构对它们的生理功能至关重要。内膜由以下部分组成 内皮细胞与多糖胞间基质交织在一起，形成血液的管腔 交通。在血管的直段中，内皮细胞(ECs)通常在 血液流动的方向。中层是血管的中间层，在那里弹性纤维，多糖， 血管平滑肌细胞(SMC)为主要分布部位。特别是，周向排列的SMC 在环形模式中控制血管的收缩/扩张，从而能够调节血流动力学。 组织工程学提供了一种很有希望的策略来修复和替换部分组织，其中血液 血管是最重要但也是最具挑战性的组织工程之一。然而，工程血管 使用基于脚手架的传统策略通常使用相对复杂的 微制造程序，不容易应用于具有复杂结构和/或小型结构的容器 大小。相比之下，三维(3D)生物打印技术的最新进展提供了 在设计血管方面具有前所未有的灵活性，分辨率高、保真度高、复杂性好。 然而，三维生物打印结构稳定和功能的血管组织是很少实现的。至 为此，我们建议开发一种独特的生物打印策略，结合数字可调微流控技术 中空纤维生物印花方法和可拉伸水凝胶生物油墨配方，以产生 在结构上、机械上和功能上仿生各种大小的非分支大血管移植物， 形状和结构，以显著促进血管移植。

Abstract Blood vessels play a critical role in the circulatory system. The main function of blood vessels is transporting blood from the heart to the rest of the tissues and organs throughout the body and then bringing it back to the heart. The structures of blood vessels are crucial to their physiological functions. The intima consists of endothelial cells, which are intertwined with a polysaccharide intercellular matrix to form the lumen for blood transportation. In straight sections of a blood vessel, endothelial cells (ECs) typically align and elongate in the direction of blood flow. The media is the middle layer in the vessels, where the elastic fibers, polysaccharides, and vascular smooth muscle cells (SMCs) are mainly located. In particular, the circumferentially aligned SMCs in ring-like patterns control the constriction/dilation of the vessels, enabling modulation of hemodynamics. Tissue engineering has provided a promising strategy to repair and replace portions of tissues, where blood vessels are one of the most important yet challenging tissue to engineer. However, engineered blood vessels using conventional strategies based on scaffolds are usually produced using relatively sophisticated microfabrication procedures, and cannot be easily applied to vessels with complex architectures and/or small sizes. In comparison, the recent advances in the three-dimensional (3D) bioprinting technology have provided unprecedented flexibility in engineering blood vessels with high resolution, strong fidelity, and good complexity. Nevertheless, 3D bioprinting of structurally stable and functional vascular tissues has rarely been achieved. To this end, we propose to develop a unique bioprinting strategy, combining the digitally tunable microfluidic hollow fiber bioprinting method and the stretchable hydrogel-based bioink formulations, to generate structurally, mechanically, and functionally biomimetic non-branching macrovascular grafts of various sizes, shapes, and structures to significantly facilitate vascular transplantation.