A review of current state-of-the-art materiobiology and technological approaches for liver tissue engineering

Chronic liver disease and related disorders are responsible for millions of deaths each year worldwide. In clinical practice, liver transplantation is recognized as an effective means of saving the lives of patients with severe complications. The shortage of organ donors has necessitated the development of bioengineered therapies that promote regeneration of the defective site and the creation of closely mimicking in vitro models for early prediction of disease states, hepatotoxicity testing, and accurate diagnostics. Despite tremendous research efforts, bioengineering of fully functional livers, detailed information on rare pathological mechanisms, and reliable bioartificial tissue-based therapies remain limited. On the other hand, 2D monolayer culture techniques are too simple to mimic and reproduce the functional characteristics of the liver accurately, its structural microenvironment, and the dynamic situation of cells in vivo. Therefore, tissue engineering-based 3D constructs outperform 2D culture systems. In this review, we provide insight into liver-related health complications, and the use of different cell types for tissue engineering. We also assess the current state of materiobiology and bioengineering technologies for fabricating 3D constructs. Afterward, we highlight the recent progress in liver tissue engineering, and outline the most relevant studies applying co-culture systems, spheroids, and organoid approaches, microfluidics, and 3D-bioprinting techniques. Finally, current dilemmas and possible future directions are explored.