Development of embedded multimaterial bioprinting platform for the biofabrication of vascular tissues

Cardiovascular diseases are one of the major causes of mortality throughout the world. Availability and suitability issues of the currently available autologous vessel and synthetic graft transplantations have created an immense need for the development of tissue engineered vascular tissue substitutes that could be benefited not only for therapeutic replacements of diseased blood vessels but also for fabrication of thick vascularized tissues and in vitro vascular disease modelling. The advent of bioprinting technology into the tissue engineering field has permitted the attainment of complexshaped tissue constructs with spatiotemporal control, unprecedented degree of precision and reproducibility when compared with conventional methodologies. However, most of the bioprinted vascular tissue substitutes still lack either the zonally stratified multimaterial composition or hierarchical complexity of native blood vessels which have been residing as major challenges in vascular tissue engineering domain and are crucial on the biofabrication of anatomically and functionally correct vascular tissue analogs. Multimaterial bioprinting is a promising technology integrating multimaterial setups into bioprinting platforms for the fabrication of multicellular, heterogeneous and functional tissue constructs. In this thesis work, a multimaterial bioprinting platform incorporating multiple-channel microfluidic multimaterial printhead was combined with the embedded bioprinting technique for the fabrication of vascular-like constructs mimicking spatial heterogeneity, multicellular and multimaterial composition and hierarchical microarchitecture of native blood vessels. Three different bioink formulations were sequentially extruded from the developed microfluidic multimaterial printhead into the prepared hydrogel-nanoclay support bath in a controlled manner, which allowed the generation of complex-shaped tubular constructs with three distinct concentric layers resembling the intimal, medial and adventitial layers of the natural vascular tissue