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

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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.