Liver Tissue Engineering: Challenges and Opportunities

Agarwal, Tarun; Subramanian, Bhuvaneshwaran; Maiti, Tapas K.

doi:10.1021/acsbiomaterials.9b00745

Cited by 61 publications

(50 citation statements)

References 152 publications

(282 reference statements)

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“…The liver is the largest internal organ, consisting of hepatocytes (major population ~ 70%), biliary epithelial cells, hepatic stellate cells, liver sinusoidal endothelial cells, Kupffer cells, and hepatic stem/progenitor cells, which are organized in unique lobular architecture and carries out over 500 different functions [96,97]. The emergence of liver organoid technology has provided a newer dimension to the pharmaceutical sector, particularly those linked with the assessment of hepatotoxic drug responses [98][99][100].…”

Section: Hepatic Organoidsmentioning

confidence: 99%

Recent advances in chemically defined and tunable hydrogel platforms for organoid culture

et al. 2021

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Recent developments in organoid culture technologies have made it possible to closely recapitulate intrinsic characteristics of different tissues under in vitro conditions. These organoids act as a translational bridge between the traditional 2D/3D cultures and the in vivo models for studying the tissue development processes, disease modeling, and drug screening. Matrigel and tissue-specific extracellular matrix have been shown to support organoid development, efficiently; however, their chemically undefined nature, non-tunable properties, and associated batch-to-batch variations often limit reproducibility of the assembly process. In this regard, chemically defined platforms offer wider opportunities to optimize and recreate tissue-specific microenvironment. The present review delineates the current research trends in this sphere, focusing on material perspective and the target tissues (e.g., neural, liver, pancreatic, renal, and intestinal). The review winds up with a discussion on the current limitations and future perspective to provide a basis for future research.

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Section: Hepatic Organoidsmentioning

confidence: 99%

Recent advances in chemically defined and tunable hydrogel platforms for organoid culture

et al. 2021

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“…Human liver cell lines derived from hepatic carcinomas such as HepG2 and Huh7 have been widely applied in toxicity test, drug screening, and physiological studies [36][37][38] . However, discrepancies exist between the cell lines and hepatocytes in the liver, making many in vitro results irreproducible in subsequent animal and clinical trials 39,40 . Accumulating evidence indicates that the way the cells are cultured in vitro can be a cause of the discrepancies 19,41 .…”

Section: Resultsmentioning

confidence: 99%

Microfibrous Extracellular Matrix Changes the Liver Hepatocyte Energy Metabolism via Integrins

Huang

Jones

Chung

et al. 2020

ACS Biomater. Sci. Eng.

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Cell line-based liver models are critical tools for liver-related studies. However, the conventional monolayer culture of hepatocytes, the most widely used in vitro model, does not have the extracellular matrix (ECM), which contributes to the three-dimensional (3D) arrangement of the hepatocytes in the liver. As a result, the metabolic properties of the hepatocytes in the monolayer tissue culture may not accurately reflect those of the hepatocytes in the liver. Here, we developed a modular platform for 3D hepatocyte cultures on fibrous ECMs produced by electrospinning, a technique that can turn a polymer solution to the micro/nanofibers and has been widely used to produce scaffolds for 3D cell cultures. Metabolomics quantitation by liquid chromatography–mass spectrometry (LC–MS) indicated that Huh7 hepatocytes grown in microfibers electrospun from silk fibroin exhibited reduced glycolysis and tricarboxylic acid (TCA) cycle, as compared to the cells cultured as a monolayer. Further mechanistic studies suggested that integrins were correlated to the ECM’s effects. This is the first time to report how an ECM scaffold could affect the fundamental metabolism of the hepatocytes via integrins.

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“…The structural and functional complexities of the native liver pose intrinsic challenges for engineering liver microtissues. [157] Unlike many other organs which carry out a relatively low number of specialized tasks, liver performs over 500 synthetic and metabolic functions. [158] It is difficult to set benchmarks against these many functional requirements, and engineered liver models must be carefully evaluated for each application.…”

Section: Discussionmentioning

confidence: 99%

Engineering Liver Microtissues for Disease Modeling and Regenerative Medicine

Huang

Gibeley

et al. 2020

Adv Funct Materials

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The burden of liver diseases is increasing worldwide, accounting for two million deaths annually. In the past decade, tremendous progress has been made in the basic and translational research of liver tissue engineering. Liver microtissues are small, 3D hepatocyte cultures that recapitulate liver physiology and have been used in biomedical research and regenerative medicine. This review summarizes the recent advances, challenges, and future directions in liver microtissue research. Cellular engineering approaches are used to sustain primary hepatocytes or produce hepatocytes derived from pluripotent stem cells and other adult tissues. 3D microtissues are generated using scaffoldfree assembly or scaffold-assisted methods such as macroencapsulation, droplet microfluidics, and bioprinting. Optimization of the hepatic microenvironment entails incorporating the appropriate cell composition for enhanced cell-cell interactions and niche-specific signals, and creating scaffolds with desired chemical, mechanical, and physical properties. Perfusion-based culture systems such as bioreactors and microfluidic systems are used to achieve efficient exchange of nutrients and soluble factors. Taken together, systematic optimization of liver microtissues is a multidisciplinary effort focused on creating liver cultures and on-chip models with greater structural complexity and physiological relevance for use in liver disease research, therapeutic development, and regenerative medicine.

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Liver Tissue Engineering: Challenges and Opportunities

Cited by 61 publications

References 152 publications

Recent advances in chemically defined and tunable hydrogel platforms for organoid culture

Recent advances in chemically defined and tunable hydrogel platforms for organoid culture

Microfibrous Extracellular Matrix Changes the Liver Hepatocyte Energy Metabolism via Integrins

Engineering Liver Microtissues for Disease Modeling and Regenerative Medicine

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