Effective vascularization is vital for survival and functionality of complex tissue-engineered organs. The formation of the microvasculature, composed of endothelial cells (ECs) alone, has been mostly used to restore the vascular networks in organs. However, recent heterocellular studies demonstrate that co-culturing is a more effective approach in revascularization of engineered organs. This review presents key considerations for manufacturing of artificial vascularized composite tissues. We summarize the importance of co-cultures and the multicellular interactions with ECs, as well as design and use of bioreactors, as critical considerations for tissue vascularization. In addition, as an emerging scaffolding technique, this review also highlights the current caveats and hurdles associated with three-dimensional bioprinting and discusses recent developments in bioprinting strategies such as four-dimensional bioprinting and its future outlook for manufacturing of vascularized tissue constructs. Finally, the review concludes with addressing the critical challenges in the regulatory pathway and clinical translation of artificial composite tissue grafts.
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