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Advanced 3D/4D Bioprinting: Integrated Technologies for Small-diameter Blood Vessel and Vascular Tissue Engineering

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Most of the current therapies for vascular disease treatments have experienced limited success due to the limitation of micro-manufacturing techniques for small-diameter (< 6 mm) blood vessel fabrication or the shortage of donors for autologous approaches. To remedy this problem, 3D and 4D (3D + shape transformation over time) bioprinting has become an emerging biomanufacturing technique to generate blood vessels and vascularized tissues in the field of vascular tissue engineering based on its exceptional controllability, reproducibility, and versatility. Hence, the main objective of this dissertation was to apply advanced 3D/4D bioprinting approaches for the development of novel biocompatible blood vessel grafts, the regeneration of vascularized tissues, and the treatment of vascular diseases. We have successfully fabricated a series of 3D monolayered- and multilayered-small-diameter blood vessel grafts to explore the mechanism of venous thrombosis and the replication of biomimetic architecture. In addition, we have created a 3D biomimetic vascularized bone tissue using a combination of two different 3D printing techniques. Moreover, 4D printed thermo-responsive cardiac patches for myocardial regeneration were fabricated. In this study, enhanced cell growth and differentiation with ideal 4D shape transformation were thoroughly demonstrated. Consequently, advanced 3D/4D bioprinting with the proper selection of biomaterials eases the fabrication steps of complex vascularization and allows us to effectively obtain highly biomimetic scaffolds for use in vascular tissue engineering.

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