3D Bioprinting of Blood Vessels and Vascular Networks: Progress and Challenges Toward Biofabrication of Functional Vascularized Tissues and Organs

Engineering of functional blood vessels and vascular capillaries that replicate the unique architecture of the human vasculature is of interest to both scientists and clinicians. Bioprinting has become a promising technology to fabricate patient-specific blood vessel-like tissue constructs, vascular grafts, as well as microvascularized tissues and organs. Despite such a promise, the successful transition of biofabricated vessels and vascularized tissue constructs from the lab to the clinic has seen limited success. Here, we revisit the biology of blood vessels and vascular structures in the body, and present some of the biological phenomena associated with building intricate vascular systems in the lab using a variety of three-dimensional (3D) printing technologies. We discuss different bioprinting approaches (extrusion, inkjet, and laser bioprinting) and the engineering challenges in fabricating blood vessels and vascularized tissues. In addition, we offer a biological perspective on current challenges and progress toward biofabrication of truly functional circulatory systems in the lab. Further, we discuss nascent technologies, such as four-dimensional (4D) bioprinting, and how they may be useful in the fabrication of vascular systems. Some key biological areas like organ-specific cells, cellular heterogeneity, genotypic, and phenotypic changes that are inherent to the printing process are also presented. Finally, we summarize how bioprinting has contributed towards the biofabrication of blood vessels and vascular networks in vitro and in vivo, and highlight the areas that are available for future investigations.