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Journal articles on the topic 'Liver-on-Chip'

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Author: Grafiati

Published: 25 May 2024

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1

Beckwitt, Colin H., Amanda M. Clark, Sarah Wheeler, D. Lansing Taylor, Donna B. Stolz, Linda Griffith, and Alan Wells. "Liver ‘organ on a chip’." Experimental Cell Research 363, no. 1 (February 2018): 15–25. http://dx.doi.org/10.1016/j.yexcr.2017.12.023.

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2

Deng, Wei, Chen, Lin, Zhao, Luo, and Zhang. "Engineered Liver-on-a-Chip Platform to Mimic Liver Functions and Its Biomedical Applications: A Review." Micromachines 10, no. 10 (October 7, 2019): 676. http://dx.doi.org/10.3390/mi10100676.

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Hepatology and drug development for liver diseases require in vitro liver models. Typical models include 2D planar primary hepatocytes, hepatocyte spheroids, hepatocyte organoids, and liver-on-a-chip. Liver-on-a-chip has emerged as the mainstream model for drug development because it recapitulates the liver microenvironment and has good assay robustness such as reproducibility. Liver-on-a-chip with human primary cells can potentially correlate clinical testing. Liver-on-a-chip can not only predict drug hepatotoxicity and drug metabolism, but also connect other artificial organs on the chip for a human-on-a-chip, which can reflect the overall effect of a drug. Engineering an effective liver-on-a-chip device requires knowledge of multiple disciplines including chemistry, fluidic mechanics, cell biology, electrics, and optics. This review first introduces the physiological microenvironments in the liver, especially the cell composition and its specialized roles, and then summarizes the strategies to build a liver-on-a-chip via microfluidic technologies and its biomedical applications. In addition, the latest advancements of liver-on-a-chip technologies are discussed, which serve as a basis for further liver-on-a-chip research.

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3

Hassan, Shabir, Shikha Sebastian, Sushila Maharjan, Ami Lesha, Anne‐Marie Carpenter, Xiuli Liu, Xin Xie, Carol Livermore, Yu Shrike Zhang, and Ali Zarrinpar. "Liver‐on‐a‐Chip Models of Fatty Liver Disease." Hepatology 71, no. 2 (February 2020): 733–40. http://dx.doi.org/10.1002/hep.31106.

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4

Kanabekova, Perizat, Adina Kadyrova, and Gulsim Kulsharova. "Microfluidic Organ-on-a-Chip Devices for Liver Disease Modeling In Vitro." Micromachines 13, no. 3 (March 10, 2022): 428. http://dx.doi.org/10.3390/mi13030428.

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Mortality from liver disease conditions continues to be very high. As liver diseases manifest and progress silently, prompt measures after diagnosis are essential in the treatment of these conditions. Microfluidic organs-on-chip platforms have significant potential for the study of the pathophysiology of liver diseases in vitro. Different liver-on-a-chip microphysiological platforms have been reported to study cell-signaling pathways such as those activating stellate cells within liver diseases. Moreover, the drug efficacy for liver conditions might be evaluated on a cellular metabolic level. Here, we present a comprehensive review of microphysiological platforms used for modelling liver diseases. First, we briefly introduce the concept and importance of organs-on-a-chip in studying liver diseases in vitro, reflecting on existing reviews of healthy liver-on-a-chip platforms. Second, the techniques of cell cultures used in the microfluidic devices, including 2D, 3D, and spheroid cells, are explained. Next, the types of liver diseases (NAFLD, ALD, hepatitis infections, and drug injury) on-chip are explained for a further comprehensive overview of the design and methods of developing liver diseases in vitro. Finally, some challenges in design and existing solutions to them are reviewed

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5

Zhang, Yao, Ning Yang, Liangliang Xie, Fangyu Shu, Qian Shi, and Naila Shaheen. "A New 3D Cultured Liver Chip and Real-Time Monitoring System Based on Microfluidic Technology." Micromachines 11, no. 12 (December 16, 2020): 1118. http://dx.doi.org/10.3390/mi11121118.

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In vitro models of the liver have a good simulation of the micro-liquid environment inside the human liver and the communication between cell tissues, which provides an important research tool for drug research and liver disease treatment. In this paper, we designed a 3D liver chip and real-time monitoring system based on microfluidic technology. The in vitro model of the liver on the chip was established by the three-dimensional microfluidic chip pipeline and the corresponding microwell array. Meanwhile, the culture medium is continuously injected on the chip, and the electrochemical impedance spectroscopy and near-infrared spectroscopy of the liver chip are recorded and analyzed from day one to day five. When the 3D cultured liver chip in vitro model reached a certain period and stabilized, paracetamol with varying gradients of concentration was applied to the cultured cells for drug resistance testing. The experimental results show that the liver chip and its monitoring system designed in this paper can maintain 100% cell viability of hepatocytes in vitro for a long time. Furthermore, it can meet the requirements of measurement technologies such as electrical impedance measurement and near-infrared spectroscopy in real-time, providing a stable culture platform for the further study of organ chips.

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6

Lasli, Soufian, Han‐Jun Kim, KangJu Lee, Ceri‐Anne E. Suurmond, Marcus Goudie, Praveen Bandaru, Wujin Sun, et al. "Liver‐on‐a‐Chip: A Human Liver‐on‐a‐Chip Platform for Modeling Nonalcoholic Fatty Liver Disease (Adv. Biosys. 8/2019)." Advanced Biosystems 3, no. 8 (August 2019): 1970084. http://dx.doi.org/10.1002/adbi.201970084.

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7

McConnon, Aili. "Liver-on-chip models mimic in vivo livers, liver disease." Scilight 2021, no. 42 (October 15, 2021): 421108. http://dx.doi.org/10.1063/10.0006843.

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8

Dabbagh, Sajjad Rahmani, Berin Ozdalgic, Nur Mustafaoglu, and Savas Tasoglu. "Three-Dimensional-Bioprinted Liver Chips and Challenges." Applied Sciences 12, no. 10 (May 16, 2022): 5029. http://dx.doi.org/10.3390/app12105029.

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Drug testing, either on animals or on 2D cell cultures, has its limitations due to inaccurate mimicking of human pathophysiology. The liver, as one of the key organs that filters and detoxifies the blood, is susceptible to drug-induced injuries. Integrating 3D bioprinting with microfluidic chips to fabricate organ-on-chip platforms for 3D liver cell cultures with continuous perfusion can offer a more physiologically relevant liver-mimetic platform for screening drugs and studying liver function. The development of organ-on-chip platforms may ultimately contribute to personalized medicine as well as body-on-chip technology that can test drug responses and organ–organ interactions on a single or linked chip model.

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9

Ferrari, Erika, and Marco Rasponi. "Liver–Heart on chip models for drug safety." APL Bioengineering 5, no. 3 (September 1, 2021): 031505. http://dx.doi.org/10.1063/5.0048986.

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10

Hong, SoonGweon, and Luke P. Lee. "Patient-Specific iPSCs-Based Liver-On-A-Chip." Biophysical Journal 106, no. 2 (January 2014): 245a. http://dx.doi.org/10.1016/j.bpj.2013.11.1438.

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11

Yang, Zhenxu, Xiaochen Liu, Elise M. Cribbin, Alice M. Kim, Jiao Jiao Li, and Ken-Tye Yong. "Liver-on-a-chip: Considerations, advances, and beyond." Biomicrofluidics 16, no. 6 (December 2022): 061502. http://dx.doi.org/10.1063/5.0106855.

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The liver is the largest internal organ in the human body with largest mass of glandular tissue. Modeling the liver has been challenging due to its variety of major functions, including processing nutrients and vitamins, detoxification, and regulating body metabolism. The intrinsic shortfalls of conventional two-dimensional (2D) cell culture methods for studying pharmacokinetics in parenchymal cells (hepatocytes) have contributed to suboptimal outcomes in clinical trials and drug development. This prompts the development of highly automated, biomimetic liver-on-a-chip (LOC) devices to simulate native liver structure and function, with the aid of recent progress in microfluidics. LOC offers a cost-effective and accurate model for pharmacokinetics, pharmacodynamics, and toxicity studies. This review provides a critical update on recent developments in designing LOCs and fabrication strategies. We highlight biomimetic design approaches for LOCs, including mimicking liver structure and function, and their diverse applications in areas such as drug screening, toxicity assessment, and real-time biosensing. We capture the newest ideas in the field to advance the field of LOCs and address current challenges.

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12

Butkutė, Agnė, Tomas Jurkšas, Tomas Baravykas, Bettina Leber, Greta Merkininkaitė, Rugilė Žilėnaitė, Deividas Čereška, et al. "Combined Femtosecond Laser Glass Microprocessing for Liver-on-Chip Device Fabrication." Materials 16, no. 6 (March 8, 2023): 2174. http://dx.doi.org/10.3390/ma16062174.

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Nowadays, lab-on-chip (LOC) devices are attracting more and more attention since they show vast prospects for various biomedical applications. Usually, an LOC is a small device that serves a single laboratory function. LOCs show massive potential for organ-on-chip (OOC) device manufacturing since they could allow for research on the avoidance of various diseases or the avoidance of drug testing on animals or humans. However, this technology is still under development. The dominant technique for the fabrication of such devices is molding, which is very attractive and efficient for mass production, but has many drawbacks for prototyping. This article suggests a femtosecond laser microprocessing technique for the prototyping of an OOC-type device—a liver-on-chip. We demonstrate the production of liver-on-chip devices out of glass by using femtosecond laser-based selective laser etching (SLE) and laser welding techniques. The fabricated device was tested with HepG2(GS) liver cancer cells. During the test, HepG2(GS) cells proliferated in the chip, thus showing the potential of the suggested technique for further OOC development.

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13

Özkan, Alican, Danielle Stolley, Erik N. K. Cressman, Matthew McMillin, Sharon DeMorrow, Thomas E. Yankeelov, and Marissa Nichole Rylander. "The Influence of Chronic Liver Diseases on Hepatic Vasculature: A Liver-on-a-chip Review." Micromachines 11, no. 5 (May 9, 2020): 487. http://dx.doi.org/10.3390/mi11050487.

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In chronic liver diseases and hepatocellular carcinoma, the cells and extracellular matrix of the liver undergo significant alteration in response to chronic injury. Recent literature has highlighted the critical, but less studied, role of the liver vasculature in the progression of chronic liver diseases. Recent advancements in liver-on-a-chip systems has allowed in depth investigation of the role that the hepatic vasculature plays both in response to, and progression of, chronic liver disease. In this review, we first introduce the structure, gradients, mechanical properties, and cellular composition of the liver and describe how these factors influence the vasculature. We summarize state-of-the-art vascularized liver-on-a-chip platforms for investigating biological models of chronic liver disease and their influence on the liver sinusoidal endothelial cells of the hepatic vasculature. We conclude with a discussion of how future developments in the field may affect the study of chronic liver diseases, and drug development and testing.

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14

Deng, Jiu, Ye Cong, Xiahe Han, Wenbo Wei, Yao Lu, Tingjiao Liu, Weijie Zhao, Bingcheng Lin, Yong Luo, and Xiuli Zhang. "A liver-on-a-chip for hepatoprotective activity assessment." Biomicrofluidics 14, no. 6 (November 2020): 064107. http://dx.doi.org/10.1063/5.0024767.

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15

Imparato, Giorgia, Brunella Corrado, Vincenza De Gregorio, Francesco Urciuolo, and Paolo Netti. "Gut-liver on chip for in vitro toxicology study." Toxicology Letters 280 (October 2017): S133. http://dx.doi.org/10.1016/j.toxlet.2017.07.371.

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16

Lee, JaeSeo, BongHwan Choi, Da Yoon No, GeonHui Lee, Seung-ri Lee, HyunJik Oh, and Sang-Hoon Lee. "A 3D alcoholic liver disease model on a chip." Integrative Biology 8, no. 3 (2016): 302–8. http://dx.doi.org/10.1039/c5ib00298b.

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17

Salmanzadeh, Alireza, and Luke P. Lee. "An Integrated Liver- and Heart-On-A-Chip Platform." Biophysical Journal 106, no. 2 (January 2014): 812a. http://dx.doi.org/10.1016/j.bpj.2013.11.4454.

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18

Fu, Jingyu, Hailong Qiu, and Cherie S. Tan. "Microfluidic Liver-on-a-Chip for Preclinical Drug Discovery." Pharmaceutics 15, no. 4 (April 21, 2023): 1300. http://dx.doi.org/10.3390/pharmaceutics15041300.

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Drug discovery is an expensive, long, and complex process, usually with a high degree of uncertainty. In order to improve the efficiency of drug development, effective methods are demanded to screen lead molecules and eliminate toxic compounds in the preclinical pipeline. Drug metabolism is crucial in determining the efficacy and potential side effects, mainly in the liver. Recently, the liver-on-a-chip (LoC) platform based on microfluidic technology has attracted widespread attention. LoC systems can be applied to predict drug metabolism and hepatotoxicity or to investigate PK/PD (pharmacokinetics/pharmacodynamics) performance when combined with other artificial organ-on-chips. This review discusses the liver physiological microenvironment simulated by LoC, especially the cell compositions and roles. We summarize the current methods of constructing LoC and the pharmacological and toxicological application of LoC in preclinical research. In conclusion, we also discussed the limitations of LoC in drug discovery and proposed a direction for improvement, which may provide an agenda for further research.

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19

Nitsche, Katharina S., Iris Müller, Sophie Malcomber, Paul L. Carmichael, and Hans Bouwmeester. "Implementing organ-on-chip in a next-generation risk assessment of chemicals: a review." Archives of Toxicology 96, no. 3 (February 1, 2022): 711–41. http://dx.doi.org/10.1007/s00204-022-03234-0.

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AbstractOrgan-on-chip (OoC) technology is full of engineering and biological challenges, but it has the potential to revolutionize the Next-Generation Risk Assessment of novel ingredients for consumer products and chemicals. A successful incorporation of OoC technology into the Next-Generation Risk Assessment toolbox depends on the robustness of the microfluidic devices and the organ tissue models used. Recent advances in standardized device manufacturing, organ tissue cultivation and growth protocols offer the ability to bridge the gaps towards the implementation of organ-on-chip technology. Next-Generation Risk Assessment is an exposure-led and hypothesis-driven tiered approach to risk assessment using detailed human exposure information and the application of appropriate new (non-animal) toxicological testing approaches. Organ-on-chip presents a promising in vitro approach by combining human cell culturing with dynamic microfluidics to improve physiological emulation. Here, we critically review commercial organ-on-chip devices, as well as recent tissue culture model studies of the skin, intestinal barrier and liver as the main metabolic organ to be used on-chip for Next-Generation Risk Assessment. Finally, microfluidically linked tissue combinations such as skin–liver and intestine–liver in organ-on-chip devices are reviewed as they form a relevant aspect for advancing toxicokinetic and toxicodynamic studies. We point to recent achievements and challenges to overcome, to advance non-animal, human-relevant safety studies.

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20

Jang, Kyung-Jin, Monicah A. Otieno, Janey Ronxhi, Heng-Keang Lim, Lorna Ewart, Konstantia R. Kodella, Debora B. Petropolis, et al. "Reproducing human and cross-species drug toxicities using a Liver-Chip." Science Translational Medicine 11, no. 517 (November 6, 2019): eaax5516. http://dx.doi.org/10.1126/scitranslmed.aax5516.

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Nonclinical rodent and nonrodent toxicity models used to support clinical trials of candidate drugs may produce discordant results or fail to predict complications in humans, contributing to drug failures in the clinic. Here, we applied microengineered Organs-on-Chips technology to design a rat, dog, and human Liver-Chip containing species-specific primary hepatocytes interfaced with liver sinusoidal endothelial cells, with or without Kupffer cells and hepatic stellate cells, cultured under physiological fluid flow. The Liver-Chip detected diverse phenotypes of liver toxicity, including hepatocellular injury, steatosis, cholestasis, and fibrosis, and species-specific toxicities when treated with tool compounds. A multispecies Liver-Chip may provide a useful platform for prediction of liver toxicity and inform human relevance of liver toxicities detected in animal studies to better determine safety and human risk.

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21

Gori, Manuele, Maria Chiara Simonelli, Sara Maria Giannitelli, Luca Businaro, Marcella Trombetta, and Alberto Rainer. "Investigating Nonalcoholic Fatty Liver Disease in a Liver-on-a-Chip Microfluidic Device." PLOS ONE 11, no. 7 (July 20, 2016): e0159729. http://dx.doi.org/10.1371/journal.pone.0159729.

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22

Lasli, Soufian, Han‐Jun Kim, KangJu Lee, Ceri‐Anne E. Suurmond, Marcus Goudie, Praveen Bandaru, Wujin Sun, et al. "A Human Liver‐on‐a‐Chip Platform for Modeling Nonalcoholic Fatty Liver Disease." Advanced Biosystems 3, no. 8 (June 14, 2019): 1900104. http://dx.doi.org/10.1002/adbi.201900104.

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23

Cong, Ye, Xiahe Han, Youping Wang, Zongzheng Chen, Yao Lu, Tingjiao Liu, Zhengzhi Wu, Yu Jin, Yong Luo, and Xiuli Zhang. "Drug Toxicity Evaluation Based on Organ-on-a-chip Technology: A Review." Micromachines 11, no. 4 (April 3, 2020): 381. http://dx.doi.org/10.3390/mi11040381.

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Organ-on-a-chip academic research is in its blossom. Drug toxicity evaluation is a promising area in which organ-on-a-chip technology can apply. A unique advantage of organ-on-a-chip is the ability to integrate drug metabolism and drug toxic processes in a single device, which facilitates evaluation of toxicity of drug metabolites. Human organ-on-a-chip has been fabricated and used to assess drug toxicity with data correlation with the clinical trial. In this review, we introduced the microfluidic chip models of liver, kidney, heart, nerve, and other organs and multiple organs, highlighting the application of these models in drug toxicity detection. Some biomarkers of toxic injury that have been used in organ chip platforms or have potential for use on organ chip platforms are summarized. Finally, we discussed the goals and future directions for drug toxicity evaluation based on organ-on-a-chip technology.

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24

Lu, Siming, Fabio Cuzzucoli, Jing Jiang, Li-Guo Liang, Yimin Wang, Mengqi Kong, Xin Zhao, Wenguo Cui, Jun Li, and ShuQi Wang. "Development of a biomimetic liver tumor-on-a-chip model based on decellularized liver matrix for toxicity testing." Lab on a Chip 18, no. 22 (2018): 3379–92. http://dx.doi.org/10.1039/c8lc00852c.

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25

Yoon No, Da, Kwang-Ho Lee, Jaeseo Lee, and Sang-Hoon Lee. "3D liver models on a microplatform: well-defined culture, engineering of liver tissue and liver-on-a-chip." Lab on a Chip 15, no. 19 (2015): 3822–37. http://dx.doi.org/10.1039/c5lc00611b.

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26

Boeri, Lucia, Luca Izzo, Lorenzo Sardelli, Marta Tunesi, Diego Albani, and Carmen Giordano. "Advanced Organ-on-a-Chip Devices to Investigate Liver Multi-Organ Communication: Focus on Gut, Microbiota and Brain." Bioengineering 6, no. 4 (September 28, 2019): 91. http://dx.doi.org/10.3390/bioengineering6040091.

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The liver is a key organ that can communicate with many other districts of the human body. In the last few decades, much interest has focused on the interaction between the liver and the gut microbiota, with their reciprocal influence on biosynthesis pathways and the integrity the intestinal epithelial barrier. Dysbiosis or liver disorders lead to0 epithelial barrier dysfunction, altering membrane permeability to toxins. Clinical and experimental evidence shows that the permeability hence the delivery of neurotoxins such as LPS, ammonia and salsolinol contribute to neurological disorders. These findings suggested multi-organ communication between the gut microbiota, the liver and the brain. With a view to in vitro modeling this liver-based multi-organ communication, we describe the latest advanced liver-on-a-chip devices and discuss the need for new organ-on-a-chip platforms for in vitro modeling the in vivo multi-organ connection pathways in physiological and pathological situations.

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27

Kulsharova, Gulsim, Akbota Kurmangaliyeva, Elvira Darbayeva, Luis Rojas-Solórzano, and Galiya Toxeitova. "Development of a Hybrid Polymer-Based Microfluidic Platform for Culturing Hepatocytes towards Liver-on-a-Chip Applications." Polymers 13, no. 19 (September 23, 2021): 3215. http://dx.doi.org/10.3390/polym13193215.

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The drug development process can greatly benefit from liver-on-a-chip platforms aiming to recapitulate the physiology, mechanisms, and functionalities of liver cells in an in vitro environment. The liver is the most important organ in drug metabolism investigation. Here, we report the development of a hybrid cyclic olefin copolymer (COC) and polydimethylsiloxane (PDMS) microfluidic (HCP) platform to culture a Huh7 hepatoma cell line in dynamic conditions towards the development of a liver-on-a-chip system. The microfluidic platform is comprised of a COC bottom layer with a microchannel and PDMS-based flat top layer sandwiched together. The HCP device was applied for culturing Huh7 cells grown on a collagen-coated microchannel. A computational fluid dynamics modeling study was conducted for the HCP device design revealing the presence of air volume fraction in the chamber and methods for optimizing experimental handling of the device. The functionality and metabolic activity of perfusion culture were assessed by the secretion rates of albumin, urea, and cell viability visualization. The HCP device hepatic culture remained functional and intact for 24 h, as assessed by resulting levels of biomarkers similar to published studies on other in vitro and 2D cell models. The present results provide a proof-of-concept demonstration of the hybrid COC–PDMS microfluidic chip for successfully culturing a Huh7 hepatoma cell line, thus paving the path towards developing a liver-on-a-chip platform.

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28

Zhu, Luyao, Changmin Shao, Hanxu Chen, Zhuoyue Chen, and Yuanjin Zhao. "Hierarchical Hydrogels with Ordered Micro-Nano Structures for Cancer-on-a-Chip Construction." Research 2021 (December 26, 2021): 1–9. http://dx.doi.org/10.34133/2021/9845679.

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In the drug therapy of tumor, efficient and stable drug screening platforms are required since the drug efficacy varies individually. Here, inspired by the microstructures of hepatic lobules, in which hepatocytes obtain nutrients from both capillary vessel and the central vein, we present a novel hierarchical hydrogel system with ordered micro-nano structure for liver cancer-on-a-chip construction and drug screening. The hierarchical hydrogel system was fabricated by using pregel to fill and replicate self-assembled colloidal crystal arrays and microcolumn array template. Due to the synergistic effect of its interconnected micro-nano structures, the resultant system could not only precisely control the size of cell spheroids but also realize adequate nutrient supply of cell spheroids. We have demonstrated that by integrating the hierarchical hydrogel system into a multichannel concentration gradients microfluidic chip, a functional liver cancer-on-a-chip could be constructed for high-throughput drug screening with good repeatability and high accuracy. These results indicated that the hierarchical hydrogel system and its derived liver cancer-on-a-chip are ideal platforms for drug screening and have great application potential in the field of personalized medicine.

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29

Ma, Li-Dong, Yi-Tong Wang, Jing-Rong Wang, Jian-Lin Wu, Xian-Sheng Meng, Ping Hu, Xuan Mu, Qiong-Lin Liang, and Guo-An Luo. "Design and fabrication of a liver-on-a-chip platform for convenient, highly efficient, and safe in situ perfusion culture of 3D hepatic spheroids." Lab on a Chip 18, no. 17 (2018): 2547–62. http://dx.doi.org/10.1039/c8lc00333e.

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30

Lungu, Iulia Ioana, and Alexandru Mihai Grumezescu. "Microfluidics – Organ-on-chip." Biomedical Engineering International 1, no. 1 (September 30, 2019): 2–8. http://dx.doi.org/10.33263/biomed11.002008.

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This review is an introduction into the world of organ-on-chip models. By briefly explaining the concept of microfluidics and ‘lab-on-chip’, the main focus is on organs-on-chip and body-on-a-chip. The usual method to test the toxicity of a drug is through animal testing. However, the results do not always correlate to humans. In order to avoid animal testing, but also attain useful results, human-derived cell cultures using microfluidics have gained attention. Among all the different types of organ-on-chip devices, this review focuses on three distinct organs: heart, skin and liver. The main requirements for each organ-on-chip, as well as recent researches are presented. There have been considerable advancements with organ-on-chip models; however, even these have their limitations. Due to the fact that the system mimics a single organ, the systemic effect of drugs cannot be fully tested. Therefore, body-on-a-chip systems have been developed; which basically are a composed of a single chip that has several chambers, each chamber accounting for a distinct organ. Multi-organ-on-chip systems have been investigated, and even commercialized, the field still being under extensive research.

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31

Kulkeaw, Kasem, and Worakamol Pengsart. "Progress and Challenges in the Use of a Liver-on-a-Chip for Hepatotropic Infectious Diseases." Micromachines 12, no. 7 (July 19, 2021): 842. http://dx.doi.org/10.3390/mi12070842.

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The liver is a target organ of life-threatening pathogens and prominently contributes to the variation in drug responses and drug-induced liver injury among patients. Currently available drugs significantly decrease the morbidity and mortality of liver-dwelling pathogens worldwide; however, emerging clinical evidence reveals the importance of host factors in the design of safe and effective therapies for individuals, known as personalized medicine. Given the primary adherence of cells in conventional two-dimensional culture, the use of these one-size-fit-to-all models in preclinical drug development can lead to substantial failures in assessing therapeutic safety and efficacy. Advances in stem cell biology, bioengineering and material sciences allow us to develop a more physiologically relevant model that is capable of recapitulating the human liver. This report reviews the current use of liver-on-a-chip models of hepatotropic infectious diseases in the context of precision medicine including hepatitis virus and malaria parasites, assesses patient-specific responses to antiviral drugs, and designs personalized therapeutic treatments to address the need for a personalized liver-like model. Second, most organs-on-chips lack a monitoring system for cell functions in real time; thus, the review discusses recent advances and challenges in combining liver-on-a-chip technology with biosensors for assessing hepatocyte viability and functions. Prospectively, the biosensor-integrated liver-on-a-chip device would provide novel biological insights that could accelerate the development of novel therapeutic compounds.

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32

Vaishnavi Shivaji Apturkar, Chaitanya Arvind Gulhane, and Pramod Vitthalrao Burakale. "Microfluidic organ-on-a-chip models of human lungs and heart: A review." GSC Biological and Pharmaceutical Sciences 24, no. 2 (August 30, 2023): 205–14. http://dx.doi.org/10.30574/gscbps.2023.24.2.0329.

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A micro-physiological system is another term for an organ-on-a-chip. Due to the idea's widespread use in drug discovery, precision medicine, and drug screening, interest in it has increased recently. The primary message of this article is to illustrate how artificial drug proof can closely imitate the human body in every regard. Important work for a biomimetic system of physiological organs based on a microfluidic chip using cell biology, engineering, and biomaterials technology. In addition, the use and effectiveness of the gut-on-a-chip, liver-on-a-chip, lung-on-a-chip, and heart-on-a-chip are examined. We have discussed the current status of this project, OOC prospects for the future, and opportunities for microfluidic devices and organs on a chip in this section.

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33

Bakuova, Nurzhanna, Sultanali Toktarkan, Darkhan Dyussembinov, Dulat Azhibek, Almas Rakhymzhanov, Konstantinos Kostas, and Gulsim Kulsharova. "Design, Simulation, and Evaluation of Polymer-Based Microfluidic Devices via Computational Fluid Dynamics and Cell Culture “On-Chip”." Biosensors 13, no. 7 (July 22, 2023): 754. http://dx.doi.org/10.3390/bios13070754.

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Organ-on-a-chip (OoC) technology has experienced exponential growth driven by the need for a better understanding of in-organ processes and the development of novel approaches. This paper investigates and compares the flow behavior and filling characteristics of two microfluidic liver-on-a-chip devices using Computational Fluid Dynamics (CFD) analysis and experimental cell culture growth based on the Huh7 cell line. The conducted computational analyses for the two chips showed that the elliptical chamber chip proposed herein offers improved flow and filling characteristics in comparison with the previously presented circular chamber chip. Huh7 hepatoma cells were cultured in the microfluidic devices for 24 h under static fluidic conditions and for 24 h with a flow rate of 3 μL·min−1. Biocompatibility, continuous flow, and biomarker studies showed cell attachment in the chips, confirming the cell viability and their consistent cell growth. The study successfully analyzed the fluid flow behavior, filling characteristics, and biocompatibility of liver-on-a-chip prototype devices, providing valuable insights to improve design and performance and advance alternative methods of in vitro testing.

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Messelmani, Taha, Anne Le Goff, Zied Souguir, Victoria Maes, Méryl Roudaut, Elodie Vandenhaute, Nathalie Maubon, Cécile Legallais, Eric Leclerc, and Rachid Jellali. "Development of Liver-on-Chip Integrating a Hydroscaffold Mimicking the Liver’s Extracellular Matrix." Bioengineering 9, no. 9 (September 5, 2022): 443. http://dx.doi.org/10.3390/bioengineering9090443.

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The 3Rs guidelines recommend replacing animal testing with alternative models. One of the solutions proposed is organ-on-chip technology in which liver-on-chip is one of the most promising alternatives for drug screening and toxicological assays. The main challenge is to achieve the relevant in vivo-like functionalities of the liver tissue in an optimized cellular microenvironment. Here, we investigated the development of hepatic cells under dynamic conditions inside a 3D hydroscaffold embedded in a microfluidic device. The hydroscaffold is made of hyaluronic acid and composed of liver extracellular matrix components (galactosamine, collagen I/IV) with RGDS (Arg-Gly-Asp-Ser) sites for cell adhesion. The HepG2/C3A cell line was cultured under a flow rate of 10 µL/min for 21 days. After seeding, the cells formed aggregates and proliferated, forming 3D spheroids. The cell viability, functionality, and spheroid integrity were investigated and compared to static cultures. The results showed a 3D aggregate organization of the cells up to large spheroid formations, high viability and albumin production, and an enhancement of HepG2 cell functionalities. Overall, these results highlighted the role of the liver-on-chip model coupled with a hydroscaffold in the enhancement of cell functions and its potential for engineering a relevant liver model for drug screening and disease study.

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Ehrlich, Avner, Daniel Duche, Gladys Ouedraogo, and Yaakov Nahmias. "Challenges and Opportunities in the Design of Liver-on-Chip Microdevices." Annual Review of Biomedical Engineering 21, no. 1 (June 4, 2019): 219–39. http://dx.doi.org/10.1146/annurev-bioeng-060418-052305.

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The liver is the central hub of xenobiotic metabolism and consequently the organ most prone to cosmetic- and drug-induced toxicity. Failure to detect liver toxicity or to assess compound clearance during product development is a major cause of postmarketing product withdrawal, with disastrous clinical and financial consequences. While small animals are still the preferred model in drug development, the recent ban on animal use in the European Union created a pressing need to develop precise and efficient tools to detect human liver toxicity during cosmetic development. This article includes a brief review of liver development, organization, and function and focuses on the state of the art of long-term cell culture, including hepatocyte cell sources, heterotypic cell–cell interactions, oxygen demands, and culture medium formulation. Finally, the article reviews emerging liver-on-chip devices and discusses the advantages and pitfalls of individual designs. The goal of this review is to provide a framework to design liver-on-chip devices and criteria with which to evaluate this emerging technology.

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Polidoro, Michela Anna, Arianna Rosina, Erika Ferrari, Marco Rasponi, Ana Lleo, and Simona Marzorati. "Cholangiorcarcinoma-on-chip: a platform for 3D liver tumour model." Journal of Hepatology 77 (July 2022): S761. http://dx.doi.org/10.1016/s0168-8278(22)01838-4.

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Kimura, Hiroshi, Takashi Ikeda, Hidenari Nakayama, Yasuyuki Sakai, and Teruo Fujii. "An On-Chip Small Intestine–Liver Model for Pharmacokinetic Studies." Journal of Laboratory Automation 20, no. 3 (June 2015): 265–73. http://dx.doi.org/10.1177/2211068214557812.

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Bhise, Nupura S., Vijayan Manoharan, Solange Massa, Ali Tamayol, Masoumeh Ghaderi, Mario Miscuglio, Qi Lang, et al. "A liver-on-a-chip platform with bioprinted hepatic spheroids." Biofabrication 8, no. 1 (January 12, 2016): 014101. http://dx.doi.org/10.1088/1758-5090/8/1/014101.

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Bovard, D., A. Sandoz, M. Morelli, K. Trivedi, D. Marescotti, S. Frentzel, K. Luettich, and J. Hoeng. "Characterization of a lung/liver organ-on-a-chip model." Toxicology Letters 295 (October 2018): S118. http://dx.doi.org/10.1016/j.toxlet.2018.06.659.

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Theobald, Jannick, Ali Ghanem, Patrick Wallisch, Amin A. Banaeiyan, Miguel A. Andrade-Navarro, Katerina Taškova, Manuela Haltmeier, et al. "Liver-Kidney-on-Chip To Study Toxicity of Drug Metabolites." ACS Biomaterials Science & Engineering 4, no. 1 (December 4, 2017): 78–89. http://dx.doi.org/10.1021/acsbiomaterials.7b00417.

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Knowlton, Stephanie, and Savas Tasoglu. "A Bioprinted Liver-on-a-Chip for Drug Screening Applications." Trends in Biotechnology 34, no. 9 (September 2016): 681–82. http://dx.doi.org/10.1016/j.tibtech.2016.05.014.

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Saleh, Anthony, Richard DeBiasio, Karlijn Wilschut, Lawrence Vernetti, D. Lansing Taylor, Paul Vulto, Albert Gough, and Anup Sharma. "High-Throughput Liver-ON-A-Chip for predictive hepatotoxicity screening." Drug Metabolism and Pharmacokinetics 34, no. 1 (January 2019): S50. http://dx.doi.org/10.1016/j.dmpk.2018.09.178.

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Dickson, Iain. "Multispecies liver-on-a-chip for improved drug toxicity testing." Nature Reviews Gastroenterology & Hepatology 17, no. 1 (November 27, 2019): 4. http://dx.doi.org/10.1038/s41575-019-0244-5.

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Moradi, Ehsanollah, Sasan Jalili-Firoozinezhad, and Mehran Solati-Hashjin. "Microfluidic organ-on-a-chip models of human liver tissue." Acta Biomaterialia 116 (October 2020): 67–83. http://dx.doi.org/10.1016/j.actbio.2020.08.041.

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Weng, Yu-Shih, Shau-Feng Chang, Ming-Cheng Shih, Shih-Heng Tseng, and Chih-Huang Lai. "Scaffold-Free Liver-On-A-Chip with Multiscale Organotypic Cultures." Advanced Materials 29, no. 36 (July 21, 2017): 1701545. http://dx.doi.org/10.1002/adma.201701545.

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Lee, Hyungseok, Suhun Chae, Jae Yun Kim, Wonil Han, Jongmin Kim, Yeongjin Choi, and Dong-Woo Cho. "Cell-printed 3D liver-on-a-chip possessing a liver microenvironment and biliary system." Biofabrication 11, no. 2 (January 16, 2019): 025001. http://dx.doi.org/10.1088/1758-5090/aaf9fa.

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Palasantzas, Victoria, Isabel Tamargo, Gwen Weijer, Alfredo Rios-Ocampo, Sebo Withoff, Johan Jonker, and Jing Fu. "Utilization of multicellular liver-on-chip to study non-alcohol-related fatty liver disease." Journal of Hepatology 78 (June 2023): S805—S806. http://dx.doi.org/10.1016/s0168-8278(23)02261-4.

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Jiao, Heng, Yuping Zhu, Shan Lu, Yongxia Zheng, and Huan Chen. "An Integrated Approach for the Identification of HNF4α-Centered Transcriptional Regulatory Networks During Early Liver Regeneration." Cellular Physiology and Biochemistry 36, no. 6 (2015): 2317–26. http://dx.doi.org/10.1159/000430195.

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Background/Aims: Hepatocyte nuclear factor-4α (HNF4α), the liver enriched transcription factor (TF), is one of the major regulators of hepatocyte differentiation and proliferation. However, how HNF4α participate in liver regeneration after partial hepatectomy (PH) remains largely unknown. In order to identify the HNF4α-centered regulatory network, we applied an integrated analytic strategy, in which, TF array, mRNA microarray, bioinformatic analysis and ChIP-on-chip assays were integrated. Methods/Results: The TF signatures from MOUSE OATFA (TF-array) platform revealed that the activity of HNF4α was significantly reduced and 17 other TFs showed increased activity at 4 h post PH. Then the ChIP-on-chip analysis on HNF4α were combined with mRNA expression profiling to select the possible HNF4α target genes during early liver regeneration, which were then sub-grouped according to their signaling pathways. More specifically, the HNF4α target genes with the gene ontology (GO) terms of cytokine-cytokine receptor, Jak-STAT, MAPK, toll-like receptor and insulin signaling pathways were further analyzed with an advanced bioinformatics tool named oPOSSUM to identify TF binding sites occupancy and predict the co-regulatory relationship between TFs and targets. Furthermore, we identified that repressed HNF4α during the early phase of liver regeneration may contribute cooperatively to the induction of immediate early genes, such as, c-fos, c-jun and stat3. Conclusion: our data indicate that HNF4α may play an inhibitory role on the induction of specific promitogenic genes and liver regeneration initiation. The integrated approach of mRNA/OATFA/ChIP-DSL/oPOSSUM analysis may help us better characterize the target genes and co-regulatory network of HNF4α during the early stage of liver regeneration.

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Thakare, Ketan, Laura Jerpseth, Zhijian Pei, Alaa Elwany, Francis Quek, and Hongmin Qin. "Bioprinting of Organ-on-Chip Systems: A Literature Review from a Manufacturing Perspective." Journal of Manufacturing and Materials Processing 5, no. 3 (August 19, 2021): 91. http://dx.doi.org/10.3390/jmmp5030091.

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This review discusses the reported studies investigating the use of bioprinting to develop functional organ-on-chip systems from a manufacturing perspective. These organ-on-chip systems model the liver, kidney, heart, lung, gut, bone, vessel, and tumors to demonstrate the viability of bioprinted organ-on-chip systems for disease modeling and drug screening. In addition, the paper highlights the challenges involved in using bioprinting techniques for organ-on-chip system fabrications and suggests future research directions. Based on the reviewed studies, it is concluded that bioprinting can be applied for the automated and assembly-free fabrication of organ-on chip systems. These bioprinted organ-on-chip systems can help in the modeling of several different diseases and can thereby expedite drug discovery by providing an efficient platform for drug screening in the preclinical phase of drug development processes.

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Polidoro, M. A., G. Saladino, E. Ferrari, M. Rasponi, S. Marzorati, and A. Lleo. "Cholangiocarcinoma-on-chip: A 3D liver tumor platform for personalized medicine." Digestive and Liver Disease 55 (March 2023): S8. http://dx.doi.org/10.1016/j.dld.2023.01.014.

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