Bioartificial livers: a review of their design and manufacture

Abstract

Acute liver failure (ALF) is a rapidly progressive disease with high morbidity and mortality rates. Liver transplantation and artificial liver support systems, such as artificial livers (ALs) and bioartificial livers (BALs), are the two major therapies for ALF. Compared to ALs, BALs are composed of functional hepatocytes that provide essential liver functions, including detoxification, metabolite synthesis, and biotransformation. Furthermore, BALs can potentially provide effective support as a form of bridging therapy to liver transplantation or spontaneous recovery for patients with ALF. In this review, we systematically discussed the currently available state-of-the-art designs and manufacturing processes for BAL support systems. Specifically, we classified the cell sources and bioreactors that are applied in BALs, highlighted the advanced technologies of hepatocyte culturing and bioreactor fabrication, and discussed the current challenges and future trends in developing next generation BALs for large scale clinical applications.

3D Printing of a Vascularized Mini‐Liver Based on the Size‐Dependent Functional Enhancements of Cell Spheroids for Rescue of Liver Failure

“…To imitate the liver lobule structure, we fabricated a biomimetic construct by 3D coaxial bioprinting of HUVECs into hexagonal vasculatures, consisting of a central vein and interconnected sinusoids, and filling the intervals with small‐sized hASC spheroids‐loaded PLdECM hydrogel as the parenchyma. [ 23 ] The use of thermosensitive PLdECM hydrogel for encapsulation of hASC spheroids was owing to their excellent maintenance of hepatocyte phenotypes and functions. [ 4 , 24 ] We found that the hepatic differentiation of hASC spheroids was more distinct when co‐cultured with HUVECs at a HUVECs/hASCs seeding density of 2:1 (Figure S18 , Supporting Information), especially for hexagonally patterned HUVECs (Figure S20 , Supporting Information).…”

Human organoids-on-chips for biomedical research and applications

“…The breakthrough highlights the importance of fluidized microchips and expands our knowledge of human embryology and reproduction. Up to now, many parts of the human body have been reproduced with OOCs, such as the brain, lung, gut, liver, kidney, islet, heart and cartilage 10 , 11 , 13 , 69 - 80 . These OOCs models have shown great promise in organ reconstitution, disease studies, drug screening, and so on 68 , 81 - 85 .…”

Schisandrin B promotes hepatic differentiation from human umbilical cord mesenchymal stem cells

“…The cell-based bioartificial liver can not only remove metabolic wastes and toxins but also provide important liver functions including metabolite synthesis and biotransformation, which is an ideal therapeutic model for artificial liver. 3 In addition, hepatocyte transplantation has been considered a feasible alternative therapy. In fact, achieving the ideal therapeutic goal of a bioartificial liver or hepatocyte transplantation relies on large-scale functional hepatocytes.…”