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 血液从心脏流到全身的其他组织和器官，然后将其带回心脏。 心血管的结构对其生理功能至关重要。内膜包括 内皮细胞，其与多糖细胞间基质交织形成血液管腔 运输在血管的直段中，内皮细胞（EC）通常在血管的横截面中排列和伸长。 血液流动的方向。中膜是血管中的中间层，其中弹性纤维，多糖， 主要分布于血管平滑肌细胞（SMC）。特别地，周向排列的SMC 以环状模式控制血管的收缩/扩张，从而能够调节血液动力学。 组织工程提供了一种有前途的策略来修复和替换部分组织，其中血液 血管是最重要但最具挑战性的组织工程之一。然而，工程血管 使用基于支架的常规策略，通常使用相对复杂的 这是由于微制造过程的复杂性，并且不能容易地应用于具有复杂结构和/或小尺寸的容器。 尺寸.相比之下，三维（3D）生物打印技术的最新进展提供了 在血管工程方面具有前所未有的灵活性，具有高分辨率、强保真度和良好的复杂性。 然而，结构稳定和功能性血管组织的3D生物打印很少实现。到 为此，我们建议开发一种独特的生物打印策略，将数字可调微流体 中空纤维生物打印方法和可拉伸的基于水凝胶的生物墨水制剂， 各种尺寸的结构、机械和功能仿生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.