RESOURCES

Abstract
This study discusses the potential for mending portions or entire hepatic to cure persistent liver disease. Fabricating functioning organs is the ultimate objective of tissue science, and this study highlights the possibility of being accomplished. The liver, the most significant gland in the human body, serves as accountable for a wide range of metabolism-related processes and activities. Persistent liver failure is a prevalent cause of mortality worldwide, and the currently prevalent technique of organ transplantation has challenges. Therefore, it is necessary to develop an artificial liver model in the laboratory that accurately replicates the natural surroundings. The generated model should be dependable in comprehending the etiology, evaluating medications, and aiding in the restoration and substitution of the impaired liver. 3-D bioprinting is a promising method that develops an in vitro model that closely resembles the in vivo environment, with the ultimate aim of being used for transplantation by tissue engineers. The technique has significant promise as a result of its exact manipulation and its capacity to uniformly disperse cells across all levels inside an intricate framework. This study provides a comprehensive examination of liver tissue engineering, specifically highlighting the use of three-dimensional bioprinting and bio-inks for liver disease models and pharmaceutical screening.

Abstract
Three-dimensional (3D) liver bioprinting is a promising technique for creating 3D liver models that can be used for in vitro drug testing, hepatotoxicity studies, and transplantation. The functional performance of 3D bioprinted liver constructs are limited by the lack of cell–cell interactions, which calls for the creation of bioprinted tissue constructs with high cell densities. This study reports the fabrication of 3D bioprinted liver constructs using a novel photocrosslinkable gelatin methacrylamide (GelMA)-based bioink formulation. However, the formation of excess free radicals during photoinitiation poses a challenge, particularly during photocrosslinking of large constructs with high cell densities. Hence, we designed a bioink formulation comprising the base polymer GelMA loaded with an antioxidant cocktail containing vitamin C (L-ascorbic acid (AA)) and vitamin E (α-tocopherol (α-Toc)). We confirmed that the combination of antioxidants loaded in GelMA enhanced the ability to scavenge intracellular reactive oxygen species formed during photocrosslinking. The GelMA formulation was evaluated for biocompatibility in vitro and in vivo. These results demonstrated that the bioink had adequate rheological characteristics and was biocompatible. Furthermore, when compared to bioprinted constructs with lower cell density, high-density primary rat hepatocyte constructs demonstrated improved cell-cell interactions and liver-specific functions like albumin and urea secretion, which increased 5-fold and 2.5-fold, respectively.

Abstract
Fabrication of functional organs is the holy grail of tissue engineering and the possibilities of repairing a partial or complete liver to treat chronic liver disorders are discussed in this review. Liver is the largest gland in the human body and plays a responsible role in majority of metabolic function and processes. Chronic liver disease is one of the leading causes of death globally and the current treatment strategy of organ transplantation holds its own demerits. Hence there is a need to develop an in vitro liver model that mimics the native microenvironment. The developed model should be a reliable to understand the pathogenesis, screen drugs and assist to repair and replace the damaged liver. The three-dimensional bioprinting is a promising technology that recreates in vivo alike in vitro model for transplantation, which is the goal of tissue engineers. The technology has great potential due to its precise control and its ability to homogeneously distribute cells on all layers in a complex structure. This review gives an overview of liver tissue engineering with a special focus on 3D bioprinting and bioinks for liver disease modelling and drug screening.