Current landscape and opportunities in the development of bioengineered in-vitro vascularized liver tissue models

The complications in liver functioning arising due to hepatic disorders are a major contributor of mortality worldwide, with transplantation being the only resort for patients with severe cases. Due to liver's direct role in drug metabolism, fabrication on functional liver tissue models is eventually becoming a necessity for high-throughput drug screening applications. Tissue engineering approaches could provide an answer to the drooping supply by allowing for the fabrication and printing of a fully operational, implantable, and sustainable liver tissues. Moreover, such bioengineered tissues can be made to resemble their native counterparts. 3D bioengineering strategies including 3D bioprinting and microfluidic-based liver-on-chip models stand out in this regard due to their potential to create physiologically relevant microenvironment/niches for the biofabricated tissues. Nonetheless, achieving vascularization in such bioengineered tissues is still considered one of the biggest bottlenecks for engineers. The incorporation of blood vessels made from endothelial cells (ECs) is addressed in vasculogenesis while angiogenesis investigates generating new vessels from preexisting vasculature. Overall, vascularization is essential for the survival, function, and integration of bioprinted liver tissues, making it a key focus area in the development of functional liver substitutes for regenerative medicine and drug testing applications. This review paper focuses on the opportunities and difficulties of performing vascularization and angiogenesis in 3D bioengineered-based liver tissue models. Particularly, this paper delves into aspects such as methods of bioengineering, bioinks used, analysis techniques, advantages, limitations, and prospects related to 3D bioengineered liver tissue models as well as vascular engineering in general.