Current Advances on 3D‐Bioprinted Liver Tissue Models

Ma, Liang; Wu, Yutong; Li, Yuting; Aazmi, Abdellah; Zhou, Hongzhao; Zhang, Bin; Yang, Huayong

doi:10.1002/adhm.202001517

Cited by 85 publications

(61 citation statements)

References 93 publications

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“…Recently, applied polymeric hydrogels have revealed poor stability and low printing accuracy; therefore, various biomixtures are being developed to enhance pre-and postprinting features as well as cytocompatibility and after-printing cellular development [1]. In this study, GelXA bioinks, which constitute a gelatin methacrylate (GelMA)-based biocompatible mixture in combination with xanthan gum and alginate, were used to enhance printability [35]. Given that GelMA has remarkable potential in controlling temporal and spatial properties, it is widely used as a 3D scaffold that plays a critical role in cell adhesion, biocompatibility and biodegradability [36].…”

Section: Discussionmentioning

confidence: 99%

Establishing a 3D In Vitro Hepatic Model Mimicking Physiologically Relevant to In Vivo State

Kang

Sarsenova

Kim

et al. 2021

Cells

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Three-dimensional (3D) bioprinting is a promising technology to establish a 3D in vitro hepatic model that holds great potential in toxicological evaluation. However, in current hepatic models, the central area suffers from hypoxic conditions, resulting in slow and weak metabolism of drugs and toxins. It remains challenging to predict accurate drug effects in current bioprinted hepatic models. Here, we constructed a hexagonal bioprinted hepatic construct and incorporated a spinning condition with continuous media stimuli. Under spinning conditions, HepG2 cells in the bioprinted hepatic construct exhibited enhanced proliferation capacity and functionality compared to those under static conditions. Additionally, the number of spheroids that play a role in boosting drug-induced signals and responses increased in the bioprinted hepatic constructs cultured under spinning conditions. Moreover, HepG2 cells under spinning conditions exhibited intensive TGFβ-induced epithelial-to-mesenchymal transition (EMT) and increased susceptibility to acetaminophen (APAP)-induced hepatotoxicity as well as hepatotoxicity prevention by administration of N-acetylcysteine (NAC). Taken together, the results of our study demonstrate that the spinning condition employed during the generation of bioprinted hepatic constructs enables the recapitulation of liver injury and repair phenomena in particular. This simple but effective culture strategy facilitates bioprinted hepatic constructs to improve in vitro modeling for drug effect evaluation.

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Section: Discussionmentioning

confidence: 99%

Establishing a 3D In Vitro Hepatic Model Mimicking Physiologically Relevant to In Vivo State

Kang

Sarsenova

Kim

et al. 2021

Cells

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“…The liver is an important organ that is largely responsible for the metabolic functions of the body (e.g., molecular anabolism, catabolism, and conversion and regulation of the energy balance), as well as detoxification and bile production. Two major blood vessels supply blood to the liver: 1) the hepatic artery and 2) the hepatic portal vein (Corsini and Bortolini, 2013;Ma et al, 2020). The liver is comprised of hexagonal structural and functional units called hepatic lobules which consist of a portal triad, hepatocytes arranged along a network of capillaries, and hepatic veins.…”

Section: Hepatic Lobule-like Models As Functional Unitsmentioning

confidence: 99%

3D Bioprinting-Based Vascularized Tissue Models Mimicking Tissue-Specific Architecture and Pathophysiology for in vitro Studies

Hwang

Choi

Jang

2021

Front. Bioeng. Biotechnol.

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A wide variety of experimental models including 2D cell cultures, model organisms, and 3D in vitro models have been developed to understand pathophysiological phenomena and assess the safety and efficacy of potential therapeutics. In this sense, 3D in vitro models are an intermediate between 2D cell cultures and animal models, as they adequately reproduce 3D microenvironments and human physiology while also being controllable and reproducible. Particularly, recent advances in 3D in vitro biomimicry models, which can produce complex cell structures, shapes, and arrangements, can more similarly reflect in vivo conditions than 2D cell culture. Based on this, 3D bioprinting technology, which enables to place the desired materials in the desired locations, has been introduced to fabricate tissue models with high structural similarity to the native tissues. Therefore, this review discusses the recent developments in this field and the key features of various types of 3D-bioprinted tissues, particularly those associated with blood vessels or highly vascularized organs, such as the heart, liver, and kidney. Moreover, this review also summarizes the current state of the three categories: (1) chemical substance treatment, (2) 3D bioprinting of lesions, and (3) recapitulation of tumor microenvironments (TME) of 3D bioprinting-based disease models according to their disease modeling approach. Finally, we propose the future directions of 3D bioprinting approaches for the creation of more advanced in vitro biomimetic 3D tissues, as well as the translation of 3D bioprinted tissue models to clinical applications.

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“…Finally, microfluidics can be interfaced with 3D printed liver tissues to control fluid shear stress and nutrient transport to the tissues. 90 …”

Section: Engineered Human Liver Models Validated For Drug Testingmentioning

confidence: 99%

Latest impact of engineered human liver platforms on drug development

2021

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Drug-induced liver injury (DILI) is a leading cause of drug attrition, which is partly due to differences between preclinical animals and humans in metabolic pathways. Therefore, in vitro human liver models are utilized in biopharmaceutical practice to mitigate DILI risk and assess related mechanisms of drug transport and metabolism. However, liver cells lose phenotypic functions within 1–3 days in two-dimensional monocultures on collagen-coated polystyrene/glass, which precludes their use to model the chronic effects of drugs and disease stimuli. To mitigate such a limitation, bioengineers have adapted tools from the semiconductor industry and additive manufacturing to precisely control the microenvironment of liver cells. Such tools have led to the fabrication of advanced two-dimensional and three-dimensional human liver platforms for different throughput needs and assay endpoints (e.g., micropatterned cocultures, spheroids, organoids, bioprinted tissues, and microfluidic devices); such platforms have significantly enhanced liver functions closer to physiologic levels and improved functional lifetime to >4 weeks, which has translated to higher sensitivity for predicting drug outcomes and enabling modeling of diseased phenotypes for novel drug discovery. Here, we focus on commercialized engineered liver platforms and case studies from the biopharmaceutical industry showcasing their impact on drug development. We also discuss emerging multi-organ microfluidic devices containing a liver compartment that allow modeling of inter-tissue crosstalk following drug exposure. Finally, we end with key requirements for engineered liver platforms to become routine fixtures in the biopharmaceutical industry toward reducing animal usage and providing patients with safe and efficacious drugs with unprecedented speed and reduced cost.

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Current Advances on 3D‐Bioprinted Liver Tissue Models

Cited by 85 publications

References 93 publications

Establishing a 3D In Vitro Hepatic Model Mimicking Physiologically Relevant to In Vivo State

Establishing a 3D In Vitro Hepatic Model Mimicking Physiologically Relevant to In Vivo State

3D Bioprinting-Based Vascularized Tissue Models Mimicking Tissue-Specific Architecture and Pathophysiology for in vitro Studies

Latest impact of engineered human liver platforms on drug development

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