Academic literature on the topic 'Liver-on-Chip'
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Journal articles on the topic "Liver-on-Chip"
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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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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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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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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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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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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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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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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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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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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.
Full textDissertations / Theses on the topic "Liver-on-Chip"
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Rathbone, Daniel Rodion. "A low volume oxygenator for open well Liver-on-a-Chip tissue culture." Thesis, Massachusetts Institute of Technology, 2018. http://hdl.handle.net/1721.1/120193.
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Thesis: S.M., Massachusetts Institute of Technology, Department of Mechanical Engineering, 2018.This electronic version was submitted by the student author. The certified thesis is available in the Institute Archives and Special Collections.
Cataloged from student-submitted PDF version of thesis.
Includes bibliographical references (pages 139-142).
MicroPhysiological Systems (MPS) show significant promise in speeding drug development and advancing basic research. They may serve better than animal models for obtaining accurate human response data and thereby reducing failed clinical trials. The CN Bio LiverChip is one such commercial MPS device which cultures liver cells on a perforated polystyrene scaffold and actively circulates cell culture medium through them. Reducing the total circulating volume is desirable to increase the concentration of difficult-to-detect compounds, improve autocrine signaling, and achieve more physiologically relevant drug decay times. However, achieving adequate oxygenation at lower volumes is challenging due to surface tension effects. This thesis describes an open-well, flow-through MPS platform with a low-volume oxygenator, at a total circulating volume of approximately 500 [mu]L. The oxygenator uses the interior corner of a hydrophilic spiral to constrain the circulating fluid and to create a thin fluid region, which decreases the diffusion depth relative to exposed surface area, thereby improving oxygenation. The oxygenator performs equivalently to the LiverChip at a fraction of the volume, and features a downward slope that prevents fluid from accumulating in the oxygenator, which could deplete the cell culture well. The fluidic configuration and other design considerations are described, as well as hardware testing results and improved methods for preventing fluid from bypassing the scaffold. This project was supported by NIH grant number UH3-TR000496.
by Daniel Rodion Rathbone.
S.M.
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Essaouiba, Amal. "Development of a liver-pancreas in vitro model using microfluidic organ-on-chip technologies." Thesis, Compiègne, 2020. http://www.theses.fr/2020COMP2573.
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Le diabète mellitus, également désigné comme la maladie du siècle, est une pathologie mortelle qui affecte le système endocrinien. Les mécanismes liés à la rupture de la boucle de rétroaction, qui régule le métabolisme et induit le diabète, ne sont pas entièrement connus. La compréhension des mécanismes d'action de l'insuline est donc essentielle pour le développement de stratégies thérapeutiques efficaces afin du lutter contre cette maladie. Par conséquent, il est impératif de trouver un modèle robuste et fiable, capable de surmonter les limites de la culture cellulaire traditionnelle en 2D et de l'expérimentation animale, pour la recherche sur le diabète. L'objectif de cette thèse est de développer un nouveau modèle de co‐culture foie‐pancréas en utilisant des systèmes microphysiologiques avancés (MPs) afin d’aborder plus efficacement le mécanisme impliqué dans la régulation endocrinienne hépatique et pancréatique. Ce travail met en évidence la capacité des systèmes multi‐organes sur puce qui combinent la compartimentation avancée des cellules en 3D, la microfluidique et la technologie des cellules souches pluripotentes induites (iPSC), pour atteindre une complexité biologique élevée et des fonctions rarement reproduites par une seule de ces technologies d’ingénierie tissulaireDiabetes mellitus (DM) or the so called disease of the century is a life threatening dysfunction that affects the endocrine system. The mechanisms underlying the break in the feedback loop that regulates the metabolism and the consequent diabetes induction are not fully known. Understanding the mechanisms of insulin action is therefore crucial for the further development of effective therapeutic strategies to combat DM. Accordingly, it is imperative to find a robust and reliable model for diabetes research able to overcome the limitations of traditional 2D in vitro cell culture and animal experimentation. The aim of this thesis is to develop a new liver‐pancreas co‐culture model using advanced microphysiological systems (MPs) to tackle more effectively the mechanism involving the hepatic and pancreatic endocrine regulation. This work highlights the power of multi organ‐on‐chip systems that combines the advanced 3D‐cell compartmentalization, microfluidics and induced pluripotent stem cells (iPSC) technology to achieve a high biological complexity and functions that are rarely reproduced by only one of these tissue engineering technologies
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Gamal, Wesam. "Real-time bioimpedance measurements of stem cellbased disease models-on-a-chip." Thesis, University of Edinburgh, 2016. http://hdl.handle.net/1842/20444.
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In vitro disease models are powerful platforms for the development of drugs and novel therapies. Stem-cell based approaches have emerged as cutting-edge tools in disease modelling, allowing for deeper insights into previously unknown disease mechanisms. Hence the significant role of these disease-in-a-dish methods in therapeutics and translational medicine. Impedance sensing is a non-invasive, quantitative technique that can monitor changes in cellular behaviour and morphology in real-time. Bioimpedance measurements can be used to characterize and evaluate the establishment of a valid disease model, without the need for invasive end-point biochemical assays. In this work, two stem cell-based disease models-on-a-chip are proposed for acute liver failure (ALF) and age-related macular degeneration (AMD). The ALF disease model-on-a-chip integrates impedance sensing with the highly-differentiated HepaRG cell line to monitor in real-time quantitative and dynamic response to various hepatotoxins. Bioimpedance analysis and modelling has revealed an unknown mechanism of paracetamol hepatotoxicity; a temporal, dose-dependent disruption of tight junctions (TJs) and cell-substrate adhesion. This disruption has been validated using ultrastructural imaging and immunostaining of the TJ-associated protein ZO-1. Age-related macular degeneration (AMD) is the leading cause of blindness in the developed world with a need for disease models for its currently incurable forms. Human induced pluripotent stem cells (hiPSCs) technology offers a novel approach for disease modelling, with the potential to impact translational retinal research and therapy. Recent developments enable the generation of Retinal Pigment Epithelial cells from patients (hiPSC-RPE), thus allowing for human retinal disease in vitro studies with great clinical and physiological relevance. In the current study, the development of a tissue-on- a-chip AMD disease model has been established using RPE generated from a patient with an inherited macular degeneration (case cell line) and from a healthy sibling (control cell line). A reproducible Electric Cell-substrate Impedance Sensing (ECIS) electrical wounding assay was conducted to mimic RPE damage in AMD. First, a robust and reproducible real-time quantitative monitoring over a 25-day period demonstrated the establishment and maturation of RPE layers on microelectrodes. A spatially-controlled RPE layer damage that mimicked cell loss in AMD was then initiated. Post recovery, significant differences in migration rates were found between case and control cell lines. Data analysis and modelling suggested this was due to the lower cell-substrate adhesion of the control cell line. These findings were confirmed using cell adhesion biochemical assays. Moreover, different-sized, individually-addressed square microelectrode arrays with high spatial resolution were designed and fabricated in-house. ECIS wounding assays were performed on these chips to study immortalized RPE migration. Migration rates comparable to those obtained with ECIS circular microelectrodes were determined. The two proposed disease-models-on-a-chip were then used to explore the therapeutic potential of the antioxidant N-Acetyl-Cysteine (NAC) on hiPSC-RPE and HepaRG cell recovery. Addition of 10 mM NAC at the end of a 24h paracetamol challenge caused a slight increase in the measured impedance, suggesting partial cell recovery. On the other hand, no effect on case hiPSC-RPE migration has been observed. More experiments are needed to examine the effect of different NAC concentrations and incubation periods. The therapeutic potential of electrical stimulation has also been explored. A preliminary study to evaluate the effect of electrical stimulation on RPE migration has been conducted. An externally applied direct current electric field (DC EF) of 300 mV/mm was found to direct the migration of the immortalized RPE cell line (hTERT-RPE1) perpendicular to the EF. The cells were also observed to elongate and to realign their long axes perpendicular to the applied EF. The proposed tissue-on-a-chip disease models are powerful platforms for translational studies. The potential of such platforms has been demonstrated through revealing unknown effects of acetaminophen on the liver as well as providing deeper insights into the underlying mechanisms of macular degeneration. Combining stem cell technology with impedance sensing provides a high throughput platform for studying patient-specific diseases and evaluating potential therapies.
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Messelmani, Taha. "Development and characterisation of a biomimetic liver on chip featuring 3D hepatic coculture with an endothelial barrier." Electronic Thesis or Diss., Compiègne, 2023. http://www.theses.fr/2023COMP2736.
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Au cours des programmes de développement de médicaments, des modèles animaux sont utilisés pour évaluer le métabolisme et la toxicité des médicaments. Plusieurs cadres juridiques sont établis pour le remplacement, la réduction et l'amélioration de ces expériences. Le foie est un organe central pour la détoxification des molécules exogènes. Par conséquent, le développement de modèles reproduisant les fonctions du foie reste un objectif ambitieux. Ces dernières années, l'association entre l'ingénierie tissulaire et la technologie des organes sur puce a conduit au développement de modèles alternatifs imitant certaines fonctions hépatiques. L'objectif de ce travail est de développer une plateforme de foie sur puce biomimétique en couplant une biopuce d'hépatocytes et une barrière endothéliale. Dans la première partie, nous avons utilisé la technologie des organes sur puce et un hydroscaffold à base de matrice extracellulaire pour organiser les cellules en 3D. Les sphéroïdes formés ont été caractérisés sur le plan structurel et fonctionnel. Dans la deuxième partie, nous avons caractérisé la formation d'une barrière endothéliale. Nous avons établi les conditions de co-culture et analysé le potentiel du couplage de la barrière endothéliale avec la puce d'hépatocytes pour métaboliser l'APAP. Enfin, nous avons analysé la signature métabolomique de chaque condition, les interactions entre les cellules et identifié la signature métabolique des lésions causées par l'APAP. Dans la dernière partie, nous avons proposé des pistes d'amélioration en utilisant des hépatocytes primaires ou en intégrant la barrière endothéliale et les hépatocytes dans une biopuce bi-comportementaliséeDuring drugs development programs, animal models are commonly used for the assessment of the metabolism and toxicity of drug candidates. Several legal frameworks are being settled to promote the replacement, the reduction, and the refinement of these experiments. The liver is a central organ involved in the detoxification of exogenous molecules. Accordingly, the development of models mimicking the functions of the liver remain a challenging objective. Conventionally, liver cells are cultured in vitro in 2D Petri dishes but this conformation leads to a rapid loss of their functions. In recent years, the association between tissue engineering and organ-on-chip technology led to the development of more accurate alternative models that mimic the liver functions. The aim of this thesis is to develop a biomimetic liver-on-chip platform by coupling a hepatocyte biochip and an endothelial-like barrier. The goal is to mimic the passage of molecules through the liver sinusoid endothelial barrier and then their metabolism with the hepatocytes. In the first part, we used organ-on-chip technology and ECM-based hydroscaffold to organise the cells in 3D structures. The potential of our model was compared with static Petri dishes and the spheroids formed were characterised structurally and functionally. In the second part, we characterized the formation of an endothelial barrier and identified specific markers indicating the conservation of the phenotype of endothelial cells. We established the coculture conditions and analysed the potential of coupling the endothelial barrier with the hepatocyte-on-chip to metabolize the APAP as a candidate molecule. Finally, we analysed the metabolomic signature of each condition, crosstalk between the cells, and identified the metabolic signature of APAP injury and described the reactions happening at metabolic level. In the last part, we proposed tracks of improvement by using primary hepatocytes or by integrating the endothelial barrier and the hepatocytes in the same bi-compartmentalized biochip
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Gröger, Marko [Verfasser], Otmar [Gutachter] Huber, Michael [Gutachter] Bauer, and Frank [Gutachter] Tacke. "Inflammation-on-a-chip : a microphysiological human liver mode / Marko Gröger ; Gutachter: Otmar Huber, Michael Bauer, Frank Tacke." Jena : Friedrich-Schiller-Universität Jena, 2018. http://d-nb.info/1177387816/34.
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Sivaraman, Anand 1977. "A microfabricated 3D tissue engineered "Liver on a Chip" : information content assays for in vitro drug metabolism studies." Thesis, Massachusetts Institute of Technology, 2004. http://hdl.handle.net/1721.1/28661.
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Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Chemical Engineering, 2004.Includes bibliographical references (p. 180-195).
(cont.) approaches to improving hepatocyte function in culture have been described, not all of the important functions--specifically the biotransformation functions of the liver--can as yet be replicated at desired in ivo levels, especially in culture formats amenable to routine use in drug development. The in vivo microenvironment of hepatocytes in the liver capillary bed includes signaling mechanisms mediated by cell-cell and cell-matrix interactions, soluble factors, and mechanical forces. This thesis focuses on the design, fabrication, modeling and characterization of a microfabricated bioreactor system that attempts to mimic the in vivo microenvironment by allowing for the three dimensional morphogenesis of liver tissue under continuous perfusion conditions. A key feature of the bioreactor that was designed is the distribution of cells into many tiny ([approximately]0.001 cm³) tissue units that are uniformly perfused with culture medium. The total mass of tissue in the system is readily adjusted for applications requiring only a few thousand cells to those requiring over a million cells by keeping the microenvironment the same and scaling the total number of tissue units in the reactor. Using a computational fluid dynamic model in ADINA® and a species conservation mass transfer model in FEMLAB®, the design of the bioreactor and the fluidic circuit was optimized to mimic physiological shear stress rates ...
Recent reports indicate that it takes nearly $800 million dollars and 10-15 years of development time to bring a drug to market. The pre-clinical stage of the drug development process includes a panel of screens with in vitro models followed by comprehensive studies in animals to make quantitative and qualitative predictions of the main pharmacodynamic, pharmacokinetic, and toxicological properties of the candidate drug. Nearly 90% of the lead candidates identified by current in vitro screens fail to become drugs. Among lead compounds that progress to Phase I clinical trials, more than 50% fail due to unforeseen human liver toxicity and bioavailability issues. Clearly, better methods are needed to predict human responses to drugs. The liver is the most important site of drug metabolism and a variety of ex vivo and in vitro model systems have therefore been developed to mimic key aspects of the in vivo biotransformation pathways of human liver-- a pre-requisite for a good, predictive pharmacologically relevant screen. Drug metabolism or biotransformation in the liver involves a set of Phase I (or p450 mediated) and Phase II enzyme reactions that affect the overall therapeutic and toxic profile of a drug. The liver is also a key site of drug toxicity following biotransformation, a response that is desirable but difficult to mimic in vitro. A major barrier to predictive liver metabolism and toxicology is the rapid (hours) loss of liver-specific functions in isolated hepatocytes when maintained under standard in itrom cell culture condition. This loss of function may be especially important in predicting toxicology, where the time scale for toxic response may greatly exceed the time scale for loss of hepatocyte function in culture. Although a wide variety of
by Anand Sivaraman.
Ph.D.
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Boulais, Lilandra. "Cryogel-integrated hepatic cell culture microchips for liver tissue engineering." Thesis, Compiègne, 2020. http://www.theses.fr/2020COMP2561.
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L’un des enjeux de l’industrie pharmaceutique aujourd’hui est de développer des modèles de foie in vitro fidèles pour améliorer la prédictivité des études précliniques, notamment l’étude de la toxicité et de l’efficacité des médicaments candidats. Ces dernières années, l’ingénierie tissulaire, approche multidisciplinaire pour développer des tissus, a mené au développement de nouvelles méthodes de culture cellulaire. Parmi elles, les cultures de cellules en 3D ou en perfusion ont permis d’obtenir des activités hépatiques similaires à celles observées in vivo. L’objectif de cette thèse est de combiner ces deux méthodes de culture cellulaire pour créer un modèle de foie in vitro encore plus fidèle. Pour cela, nous cherchons à développer un cryogel d’alginate intégré en micropuce avec des propriétés mécaniques adaptables à celles du foie en fonction de l’état physiologique à reproduire (foie sain ou pathologique). Dans la première partie, nous développons et caractérisons le cryogel d’alginate au niveau microscopique et macroscopique, à l’extérieur (échantillons cylindriques) puis à l’intérieur de la biopuce. Trois paramètres sont étudiés ici : la température de cryopolymérisation, la concentration d’alginate ainsi que la quantité d’agents réticulants. Les propriétés mécaniques, la porosité, l’absorption, l’interconnectivité des pores et la résistance au flux sont analysés.La deuxième partie vise à cultiver des cellules hépatiques au sein de ce nouveau dispositif. Pour cette étude de faisabilité la lignée cellulaire HepG2/C3A est utilisée. Les résultats montrent des cellules viables et fonctionnelles (production d’albumine, transformation d’APAP). De plus, nous observons une structure tissulaire 3D, qui se maintient après retrait du cryogel d’alginate. La dernière partie a pour but de complexifier le modèle hépatique, notamment par des co-cultures. Pour se rapprocher de la structure du sinusoïde, des cellules hépatiques sont cultivées avec des cellules endothéliales (HUVEC) selon deux approches. De plus, la possibilité de suivre des cellules tumorales circulantes (MDA-MB-231) dans le système est étudiéeToday, one of the challenges for the pharmaceutical industry is to develop accurate in vitro liver models to improve the predictability of preclinical studies, in particular the study of the toxicity and efficacy of drug candidates. In recent years, tissue engineering, a multidisciplinary approach to develop tissues, has led to the development of new cell culture methods. Among them, cell cultures in 3D or in perfusion allowed to obtain hepatic activities similar to those observed in vivo. The objective of this thesis is to combine these two cell culture methods to create an even more accurate in vitro liver model. To do so, we are seeking to develop an alginate cryogel integrated into a microchip with mechanical properties adaptable to those of the liver depending on the physiological state to be reproduced (healthy or pathological liver).In the first part, we develop and characterize the alginate cryogel at the microscopic and macroscopic level, outside (cylindrical samples) and then inside the biochip. Three parameters are studied here: the cryopolymerization temperature, the alginate concentration and the quantity of cross-linking agents. Mechanical properties, porosity, absorption, pore interconnectivity and flow resistance are analyzed. The second part aims to culture liver cells within this new device. For this feasibility study the HepG2/C3A cell line is used. The results show viable and functional cells (albumin production, APAP transformation). In addition, we observe a 3D tissue structure, which is maintained after removal of the alginate cryogel. The last part aims to complexify the hepatic model, in particular by co-cultures. To get closer to the sinusoid structure, liver cells are cultured with endothelial cells (HUVEC) according to two approaches. In addition, the possibility to follow circulating tumor cells (MDA-MB-231) in the system is studied
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Madiedo-Podvršan, Sabrina. "Development of a lung-liver in vitro coculture model for the risk assessment of inhaled xenobiotics." Electronic Thesis or Diss., Compiègne, 2022. http://www.theses.fr/2022COMP2703.
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L’urbanisation et la mondialisation sont des phénomènes de société qui multiplient et complexifient les sources de pollution. Parmi elles, la pollution atmosphérique impacte notablement la santé humaine à l’échelle mondiale de par son caractère transfrontière. L’appareil respiratoire est une voie d’absorption de nombreux xénobiotiques, sous forme de gaz, d’aérosols ou de nanoparticules. Une fois dans les voies respiratoires, les substances inhalées sont susceptibles d’interagir avec les cellules pulmonaires. Les mécanismes par lesquels des xénobiotiques inhalés induisent des dommages pulmonaires sont complexes, notamment en raison de l’hétérogénéité cellulaire des poumons. En raison de cette complexité, les modèles animaux constituent un outil de référence pour les études toxicologiques prédictives, cependant, dans le contexte européen de réduction de l’expérimentation animale (REACH, et les règles 3R), le développement de méthodes alternatives fiables est devenu une nécessité. Les modèles in vitro sont de bons candidats car plus simple et moins couteux à mettre en oeuvre que les modèles vivo et permettent de travailler avec des cellules ou des tissus d’origine humaine ce qui contribue à améliorer la pertinence des résultats. Cependant, l’extrapolation limitée du vitro au vivo est souvent liée à un manque de complexité des modèles, notamment en raison de l’absence de communication inter-organes. Les technologies des multi-organes sur puce cherchent à surmonter ces limitations en connectant plusieurs organoïdes métaboliquement actifs au sein d’un même circuit de culture afin de reproduire des interactions de type systémiques. Dans ce contexte, nous décrivons un modèle permettant de connecter in vitro, par le biais de la microfluidique, une barrière pulmonaire (voie d’entrée des xénobiotiques inhalés) à un organe détoxifiant tel que le foie, afin d’évaluer la toxicité liée à un stress inhalatoire de façon plus systémique. Cette approche permet de considérer la biotransformation des composés inhalés et l’interaction inter-organes comme possible modulateurs de la toxicité. Le projet étant dans les premières phase de développement, la robustesse expérimentale était au coeur du projet. L’objectif principal était de prouver qu’une substance modèle était capable de transiter dans le dispositif, au travers des deux compartiments tissulaires, afin de pouvoir étudier la dynamique inter-organes poumon/foie en condition de stress xénobiotique. Le projet a été articulé en trois phases expérimentales : - Caractérisation des réponses biologiques spécifiques aux tissus pulmonaire et hépatique en réponse à un stress. La viabilité, la fonctionnalité et les activités métaboliques des monocultures ont été évaluées après exposition à une substance modèle. - Adaptation et préparation des monocultures aux conditions de co-culture afin de préserver la viabilité et la fonctionnalité des tissus. - Les compartiments pulmonaire et hépatique ont été cultivés jointement dans un circuit de culture microfluidique fermé. La co-culture a été exposée à une substance modèle à travers la barrière pulmonaire afin d’imiter un mode d’exposition inhalatoire. Les paramètres de viabilité et de fonctionnalité des tissus ont été évalué post-culture afin de mettre en évidence quelconque phénomène d’interaction inter-organe. La caractérisation du modèle de co-culture a été réalisé grâce à l’exposition d’un agent hépatotoxique de référence, largement étudié dans la littérature : l’acétaminophène aussi connu sous le nom de paracétamol (APAP). L’exposition à la barrière pulmonaire n’est pas physiologique mais permet d’observer quantitativement le passage et la circulation du xénobiotique à travers le dispositif car l’APAP interfère avec la viabilité et les performances métaboliques hépatique, permettant ainsi de vérifier que le compartiment hépatique peut avoir accès à l’exposition effectuée à travers la barrière pulmonaireUrbanization and globalization are prevailing social phenomena that multiply and complexify the sources of modern pollution. Amongst others, air pollution has been recognized as an omnipresent life-threatening hazard, comprising a wide range of toxic airborne xenobiotics that expose man to acute and chronic threats. The defense mechanisms involved in hazardous exposure responses are complex and comprise local and systemic biological pathways. Due to this complexity, animal models are considered prime study models. However, in light of animal experimentation reduction (3Rs), we developed and investigated an alternative in vitro method to study systemic-like responses to inhalationlike exposures. In this context, a coculture platform was established to emulate interorgan crosstalks between the pulmonary barrier, which constitutes the route of entry of inhaled compounds, and the liver, which plays a major role in xenobiotic metabolism. Both compartments respectively comprised a Calu-3 insert and a HepG2/C3A biochip which were jointly cultured in a dynamically-stimulated environment for 72 hours. The present model was characterized using acetaminophen (APAP), a well-documented hepatotoxicant, to visibly assess the passage and circulation of a xenobiotic through the device. Two kinds of models were developed: (1) the developmental model allowed for the technical setup of the coculture, and (2) the physiological-like model better approximates a vivo environment. Based on viability, and functionality parameters the developmental model showed that the Calu-3 bronchial barrier and the HepG2/C3A biochip can successfully be maintained viable and function in a dynamic coculture setting for 3 days. In a stress-induced environment, present results reported that the coculture model emulated active and functional in vitro crosstalk that seemingly was responsive to high (1.5 and 3 mM) and low (12 and 24 μM) xenobiotic exposure doses. Lung/liver crosstalk induced modulation of stress response dynamics, delaying cytotoxicity, proving that APAP fate, biological behaviors and cellular stress responses were modulated in a broader systemic-like environment
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Weng, Yu-Shih, and 翁育詩. "Scaffold-free liver-on-a-chip with multiscale organotypic cultures." Thesis, 2018. http://ndltd.ncl.edu.tw/handle/xxvgd5.
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博士國立清華大學
材料科學工程學系
106
The considerable advances that have been made in the development of organotypic cultures have failed to overcome the challenges of expressing tissue specific functions and complexities, especially for organs that require multitasking and complex biological processes, such as the liver. Primary liver cells are ideal biological building blocks for functional organotypic reconstruction, but are limited by their rapid loss of physiological integrity in vitro. Here, we apply the concept of lattice growth used in material science to develop a tissue incubator which provides physiological cues and controls the three dimensional assembly of primary cells. The cues include a biological growing template, spatial co-culture, biomimetic radial flow and circulation in a scaffold-free condition. We demonstrate the feasibility of recapitulating a multiscale physiological structural hierarchy, complex drug clearance, and zonal physiology from the cell to tissue level in long-term cultured liver-on-a-chip (LOC). Our methods are promising for future applications in pharmacodynamics and personal medicine.
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Wu, Chia-Chun, and 吳嘉浚. "Liver-on-chip: Primary rat small hepatocytes in amicrofluidic platform." Thesis, 2018. http://ndltd.ncl.edu.tw/handle/w9z499.
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碩士國立臺灣大學
生物產業機電工程學研究所
106
The liver is an organ with vital functions, including energy storage, secretion protein synthesis, and especially metabolism of pharmaceutical drugs. However, in vitro studies of drug test are usually limited to precisely evaluate the real influences on hepatic tissue because it is an obstacle to develop a platform which can sophisticatedly mimic in vivo hepatic environment. Thus, in this study we established a microenvironment-mimicking liver-on-chip (LOC) platform for in vitro hepatotoxicity test. Small hepatocytes, which have been identified in primary hepatocyte cultures with high potential for proliferation and differentiation into mature hepatocytes, was used as cell source for LOC platform. The result shows that small hepatocytes can survive in 2D primary cultures, and form 300-400 μm colonies for maintaining hepatocyte functions. Compared to primary hepatocytes, which normally maintain their function for about 7 days, small hepatocytes can survive at least 4 weeks. We analyzed the gene expression of small hepatocytes by q-PCR. Expression of albumin and Tryptophan 2,3-dioxygenase (marker of primary hepatocytes) are 3 times and 120 times increase, whereas Follistatin (marker of small hepatocytes) expression is 0.4 times decrease, after 2 weeks of culture. We also analyzed the RNA expression by NGS. The expression of CK18 and CK19 increase 2 times whereas CD44 decreases 7 times, after 2 weeks of culture. On the other hand, poly(methyl methacrylate) was utilized to fabricate microfluidic devices. The substrates are patterned using the laser cutter, and bonded in a commercial microwave.Compared to the traditional PDMS fabrication process (usually needs 1~2 days), this bonding process is very simple and can therefore save more time (only 3~4 hours)). Besides, the viability of small hepatocytes in poly(methyl methacrylate)-microfluidic devices is 27% higher than that in 2D primary cultures. In summary, the small hepatocytes-derived liver-on-chip platform was successfully developed and therefore can simulate the real environment in model animals, and also build toxicology database and make safety assessment of drugs, chemicals and pesticides in the future.
Book chapters on the topic "Liver-on-Chip"
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George, Evelyn, Shiny Velayudhan, and P. R. Anil Kumar. "Liver-on-a-Chip." In Microfluidics and Multi Organs on Chip, 341–57. Singapore: Springer Nature Singapore, 2022. http://dx.doi.org/10.1007/978-981-19-1379-2_15.
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Kulkeaw, Kasem. "Design of a Liver-on-a-Chip." In Emergence of In Vitro 3D Systems to Model Human Malaria, 67–81. Singapore: Springer Nature Singapore, 2023. http://dx.doi.org/10.1007/978-981-99-0691-8_5.
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Mirzababaei, Soheyl, Mona Navaei-Nigjeh, Mohammad Abdollahi, and Amir Shamloo. "Liver-on-a-chip." In Principles of Human Organs-on-Chips, 195–249. Elsevier, 2023. http://dx.doi.org/10.1016/b978-0-12-823536-2.00011-0.
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Du, Yu, Ning Li, and Mian Long. "Liver sinusoid on a chip." In Methods in Cell Biology, 105–34. Elsevier, 2018. http://dx.doi.org/10.1016/bs.mcb.2018.06.002.
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Douglas, Kenneth. "Organs-on-a-Chip." In Bioprinting, 155–82. Oxford University Press, 2021. http://dx.doi.org/10.1093/oso/9780190943547.003.0010.
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Abstract: This chapter explores organs-on-a-chip, miniaturized bioprinted organ tissues enclosed in a microfluidic housing (microfluidics refers to very small-scale plumbing) that can mimic functions of human physiology or disease and are particularly effective when multiple tissue types—for example, lung, heart, and liver—can interact on the same chip. The chapter sets forth the historical evolution of organs-on-a-chip and instances several studies. In one investigation, experimenters found a totally unexpected result in which a drug produced an inflammation of lung tissue that in turn led to toxic results in nearby heart tissue. In another inquiry, researchers focused on a bioprinted, functional, airway-on-a-chip to characterize inflammatory diseases such as asthma and chronic obstructive lung disease and vet potential medications for their treatment. Their work included quantitative comparisons of normal lung tissue and asthmatic lung tissue to a variety of insults, including household dust mites.
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Ishida, Seiichi. "Requirements for designing organ-on-a-chip platforms to model the pathogenesis of liver disease." In Organ-on-a-chip, 181–213. Elsevier, 2020. http://dx.doi.org/10.1016/b978-0-12-817202-5.00005-x.
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Sung, Jong Hwan. "A body-on-a-chip (BOC) system for studying gut-liver interaction." In Methods in Cell Biology, 1–10. Elsevier, 2020. http://dx.doi.org/10.1016/bs.mcb.2020.01.003.
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"Liver Cancer." In Medical Sensors and Lab-on-a-Chip Devices, 387–406. WORLD SCIENTIFIC, 2018. http://dx.doi.org/10.1142/9789813221246_0020.
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"Liver Function Tests." In Medical Sensors and Lab-on-a-Chip Devices, 577–87. WORLD SCIENTIFIC, 2018. http://dx.doi.org/10.1142/9789813221246_0029.
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A., Kodieswari. "Early Detection of Cancer Using Smartphones." In Advances in Medical Technologies and Clinical Practice, 25–31. IGI Global, 2021. http://dx.doi.org/10.4018/978-1-5225-6067-8.ch003.
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Cancer disease is the second largest disease in the world with high death mortality. Cancer is an abnormal growth of a normal cell. There are more than 100 types of cancer like blood cancer, brain cancer, small intestine cancer, lung cancer, liver cancer, etc. The type of cancer can be classified by the type of cell which is initially affected. When cancer grows it does not show any symptom. The symptom will appear when the cancer cell grows in mass and the symptom of cancer depends on the type of cancer. The cause of cancers is environmental pollutants, food habits, inherited genetics, tobacco, stress, etc., but in practice, it is not possible to prove the cause of cancer since various cancers do not have specific fingerprints. After the heart attack, cancer is a second killer disease in India. The death mortality is high in cancer because in most of the cases it is identified at the final stage which causes more death. According to ICMR, among 1.27 billion Indian populations, the incidence of cancer is 70-90 per 100,000 populations and 70% of cancer is identified in the last stage accounting for high morality. There are many types of treatment to treat cancer and they are surgery, radiation therapy, chemotherapy, targeted therapy, hormone therapy, stem cell transplant, etc. All cancer treatments will have side effects and the treatments will help only if the cancer cells are identified at the early stage. So time factor is important in diagnosing of cancer cells; hence, early detection of cancer will reduce the mortality rate. This chapter proposed the early detection of cancer cells using image processing techniques by the structure of circulating tumor cell. Early detection of cancer cells is very difficult because the concentration of cancer cells are extremely small and about one million malignant cell is encountered per billion of healthy cells. The circulating tumor cells, CTC, are shed into the bloodstream as a tumor grows, and it is believed these cells initiate the spread of cancer. CTC are rare, existing as only a few per one billion blood cells, and a highly efficient technology like chip-based biosensor platforms is required to capture the CTC, which in turn helps to detect cancer cell at an early stage before spreading. In proposed method, the circulating tumor cell has used a marker to detect cancer at early stage.
Conference papers on the topic "Liver-on-Chip"
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Kang, Y. B., T. R. Sodunke, J. Cirillo, M. J. Bouchard, and H. Noh. "Liver on a chip: Engineering the liver sinusoid." In 2013 Transducers & Eurosensors XXVII: The 17th International Conference on Solid-State Sensors, Actuators and Microsystems (TRANSDUCERS & EUROSENSORS XXVII). IEEE, 2013. http://dx.doi.org/10.1109/transducers.2013.6626762.
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Liu, C. H. "Lobule-mimetic Reconstruction on a Liver Lab Chip." In 2012 International Conference on Solid State Devices and Materials. The Japan Society of Applied Physics, 2012. http://dx.doi.org/10.7567/ssdm.2012.i-9-1.
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Oki, Akio, Hiroki Ogawa, and Yasuhiro Horiike. "γ-GTP Colorimetric Measurement on a Microcapillary Chip for Testing Liver." In 2002 International Conference on Solid State Devices and Materials. The Japan Society of Applied Physics, 2002. http://dx.doi.org/10.7567/ssdm.2002.f-6-2.
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Alex, Aneesh, Terrence Roh, BanuPriya Sridharan, Jindou Shi, Prabuddha Mukherjee, Eric J. Chaney, James Tunstead, et al. "Label-free multimodal multiphoton imaging of Liver-on-a-Chip models." In Label-free Biomedical Imaging and Sensing (LBIS) 2022, edited by Natan T. Shaked and Oliver Hayden. SPIE, 2022. http://dx.doi.org/10.1117/12.2608861.
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Butola, Ankit, David A. Coucheron, Karolina Szafranska, Azeem Ahmad, Hong Mao, Jean-Claude Tinguely, Peter McCourt, et al. "Quantitative phase imaging and on-chip nanoscopy for 3D imaging of liver sinusoidal endothelial cells." In Digital Holography and Three-Dimensional Imaging. Washington, D.C.: Optica Publishing Group, 2022. http://dx.doi.org/10.1364/dh.2022.w4a.2.
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We present a highly spatially sensitive quantitative phase microscopy system integrated with on-chip nanoscopy to visualize 3D morphology of liver sinusoidal endothelial cells (LSECs). We used the system to obtain 3D morphology of LSEC by using chip-based nanoscopy for lateral super-resolution, and QPM for mapping nanoscale thickness.
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Pinto, Edgar, Violeta Carvalho, Nelson Rodrigues, Raquel O. Rodrigues, Rui A. Lima, and Senhorinha Teixeira. "Optimization of the Flow Parameters for a Liver Organ-on-a-Chip Computational Model." In ASME 2023 International Mechanical Engineering Congress and Exposition. American Society of Mechanical Engineers, 2023. http://dx.doi.org/10.1115/imece2023-113639.
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Abstract The organ-on-a-Chip (OOC) concept appeared intending to increase the efficiency and effectiveness of R&D activities, and open doors to precision and personalized medicine. However, for such devices to provide adequate results, they must mimic a specific human microenvironment with great accuracy. In the present work, a computational model of an organ-on-a-chip model was developed and optimized by evaluating the effectiveness and characteristics of some optimization methods. To perform the optimization and simulation, a geometry appropriate to the needs was first designed, having in base the current literature. After that, a mesh set capable of maintaining a balance between the accuracy of the results and computational performance was generated and a mesh study was conducted. Then, the simulation and optimization were performed. The latter was conducted by applying two different methods, the Multi-Objective Genetic Algorithm (MOGA) and Nonlinear Programming by Quadratic Lagrangian (NLPQL), for later comparison of results. Bearing in mind the hemodynamics in the liver, the goal of this optimization was to minimize the organ model blood flow mean velocity, in order to allow the adequate transfer of substances between the blood and liver cells.
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Yang, Jiandong, Satoshi Imamura, Yoshikazu Hirai, Ken-ichiro Kamei, Toshiyuki Tsuchiya, and Osamu Tabata. "Multilayered Microfluidic Device for Controllable Flow Perfusion of Gut-Liver on a Chip." In 2021 21st International Conference on Solid-State Sensors, Actuators and Microsystems (Transducers). IEEE, 2021. http://dx.doi.org/10.1109/transducers50396.2021.9495477.
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Carvalho, Violeta, Nelson Rodrigues, Raquel O. Rodrigues, José C. Teixeira, João Miranda, Rui A. Lima, and Senhorinha Teixeira. "Influence of the Inlet Velocity on Oxygen Gradients in a Liver-on-a-Chip Model." In ASME 2022 International Mechanical Engineering Congress and Exposition. American Society of Mechanical Engineers, 2022. http://dx.doi.org/10.1115/imece2022-96001.
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Abstract Cancer continues to be one of the diseases that most affect the population around the world and different lines of research have been conducted to develop new therapies. However, a critical problem in this process is the lack of suitable in vitro preclinical platforms to assess the drug targets, toxicity, and efficacy. In order to surpass these issues, organ-on-a-chip (OoC) platforms emerged as a potential alternative for two-dimensional in vitro models, and computational simulations have played an important role. This tool boosts and supports the development process of OoC devices. Moreover, through numerical simulations, an overview of the fluid flow can be obtained which is useful for getting insights about the expected experimental results. Nevertheless, attention must be taken when defining the boundary conditions, fluid properties, and solution methods among other parameters that will affect the end results. In this regard, the aim of the present work is to evaluate the influence of varying the boundary conditions on the oxygen gradients along the liver-on-a-chip, namely imposing different velocities at the inlet and considering or not the convective term. It was found that for the OoC tested, by increasing the inlet velocity, the dissolved oxygen that reaches the organoids decreases.
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Atiyat, Samah A., and Shadi M. Karabsheh. "Liver-on-a-Chip for Evaluating Hepatic Activation of Clopidogrel in Patients with Coronary Stents." In Biomedical Engineering. Calgary,AB,Canada: ACTAPRESS, 2017. http://dx.doi.org/10.2316/p.2017.852-026.
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Tian, Tian, Chen Chen, and Hongju Mao. "A 3D BIO-PRINTED SPHEROIDS BASED PERFUSION IN VITRO LIVER ON CHIP FOR DRUG SCREENING." In 2021 21st International Conference on Solid-State Sensors, Actuators and Microsystems (Transducers). IEEE, 2021. http://dx.doi.org/10.1109/transducers50396.2021.9495562.
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