Mechanically active organonachip microdevices that reconstitute tissue tissue interfaces critical to organ function may therefore expand the. Modeling a lungonachip microdevice comsol multiphysics. A specific amount of air is sealed in the air chamber and. Pharmacokinetic profile that reduces nephrotoxicity of. Ronaldsonbouchard and vunjaknovakovic discuss the design considerations for single and multi organ organs on a chip oocs and highlight the potential impact of oocs as a fasttrack opportunity for tissue engineering to advance drug development and precision medicine.
Jan 28, 2019 syringe pumps are commonly used in microfluidic systems to provide flows with precise control. Development of a functional glomerulus at the organ level on. The lungonachip is a complex, threedimensional model of a living, breathing human lung on. Faculty of evaluation for reconstituting organ level lung functions on a chip. Reconstituting organlevel lung functions on a chip. This paper presents a microfluidic stabilizer which contains an air chamber.
A human disease model of drug toxicityinduced pulmonary. Human organ chip models recapitulate orthotopic lung cancer. The first breakthrough organonachip model that recreated organ biomechanics was a breathing lungonachip that used a lateral vacuum to exert strain on a thin flexible membrane and stimulate the lung epithelial cell barrier 7. This bile duct on a chip captured essential features of a simplified bile duct in structure and organ level functions and represents an in vitro platform to study the pathophysiology. Researchers develop living, breathing human lungonachip date. In this study we are introducing an efficient alveolus on a chip for reconstituting this environmental condition in a. Elabbasi1 1veryst engineering, needham, ma, usa abstract organ on a chip microdevices combine microfluidics, mems, and biotechnology. Bioprinting technology, which can precisely control the organization of cells, biomolecules, and the. A liveronachip platform with bioprinted hepatic spheroids. Here we describe the development of a human lung small airway on a. Reconstituting organ level lung functions n a chip.
Most organonachip models today only culture one cell type, so even though they may be valid models for studying whole organ functions, the systemic effect of a drug on the human body is not verified. Apr 20, 2016 these tissue organoids include liver organoids with metabolic activity, contracting skeletal and cardiac muscle constructs, gut, kidney, and brain constructs. Organbodyonachip based on microfluidic technology for. In particular, an integrated cell culture analog cca was developed and included lung cells, drugmetabolizing liver and fat cells.
Advanced modeling of a lung on a chip microdevice m. But small periodic fluctuations on flow induced by the stepper motor in syringe pumps are a problem that influences the characteristics of the microfluidic system. Jun 25, 2010 reconstituting organ level lung functions on a chip. The recent emergence of organs on a chip opens new opportunities in cell biology by uniquely reproducing key aspects of the invivo cellular microenvironment. The device is made using human lung and blood vessel cells and it can predict absorption of airborne nanoparticles and mimic the inflammatory response triggered by microbial pathogens. Jan 31, 2020 in contrast, in the organonachip corpus, the top 10 cited organonachip documents harvested 4605 citations, representing 26. A bile ductonachip with organlevel functions request pdf. Matthews and akiko mammoto and mart\in montoyazavala and hong yuan hsin and donald e. Reconstituting organ level lung functions on a chip dongeun huh,1,2 benjamin d. These conditions similarly affect cultured cells and may influence their ability to respond appropriately to physiological or pathological stimuli. Global trends of organoid and organonachip in the past. In nanotoxicology studies, this lung mimic revealed that cyclic mechanical strain accentuates toxic and. Successful establishment of primary type ii alveolar.
Faculty of evaluation for reconstituting organlevel lung functions on a chip. If you wish to distribute this article to others, you can order highquality copies for your following the guidelines here. The lung is comprised of more than 40 resident cell types, each with specific physiologic functions. For vessel on a chip model, conventional fabrication techniques are unable to efficiently imitate the intimalmedial unit of the vessel wall. Frontiers from petri dishes to organ on chip platform.
Organonachip microdevices combine microfluidics, mems, and. The two main types of lung cancersmall cell and nonsmall cellgrow and spread in different ways, and each type may be treated differently. Small airwayonachip enables analysis of human lung. The organ on a chip has the advantage over 2d cell culture that the cellular microenvironment can be engineered in a more physiological state including the mechanical microenvironment 9. The two most important cell types are epcs to line the airway lumina and ecs to line the pulmonary vasculature. Researchers develop living, breathing human lungonachip. Jun 25, 2010 similar effects of physiological breathing on nanoparticle absorption are observed in whole mouse lung. This bioinspired microdevice reproduces complex integrated organ level responses to bacteria and inflammatory cytokines introduced into the alveolar space. The increasing interest for microfluidic devices in medicine and biology has opened the way to new timelapse microscopy era where the amount of images and their acquisition time will become crucial.
We herein provide a background of microfluidic systems, organ on a chip, body on a chip technologies, and their challenges in the future. At the multicellular level, organ on a chip approaches in the future will incorporate multiple cell types, vascular networks, and more complex spatial geometries and bioinks to better mimic physiological tissue complexity. Clearly as the system goes from single organ and 2d to multiple organ and 3d, the complexity and variables requiring control and optimization become more onerous. Biodegradable scaffold with built in vasculature for organ ona chip engineering and direct surgical anas tomosis. Pdf reconstituting organlevel lung functions on a chip. Chip reconstituting organ level lung functions on a this copy is for your personal, noncommercial use only.
Lung cancer is a disease caused by the abnormal growth of cells. An airchamberbased microfluidic stabilizer for attenuating. The lung on a chip is a complex, threedimensional model of a living, breathing human lung on a microchip. The authors cultured two types of human lung cells in parallel microchannels, which were separated by a thin membrane. Visionaries imagine the eventual development of a personalized human on a chip system where a minimum number of organs are integrated to produce an amazing testing system of the future. Reconstituting organlevel lung functions on a chip science. This copy is for your personal, noncommercial use only. The program has produced many tangible outcomes in tissue chip development in terms of stem cell differentiation, microfluidic engineering, platform development, and single and multiorgan systemsand continues to help facilitate the acceptance and use of tissue chips by the wider community. Aug 25, 2016 development of a functional glomerulus at the organ level on a chip to mimic hypertensive nephropathy.
In vitro cancer models often fail to faithfully recapitulate the local tissue and organ microenvironment. Here, we describe a biomimetic microsystem that reconstitutes the critical functional alveolarcapillary interface of the human lung. Following a period of twoweeks, increased epithelial surfactant production was induced by the continuous. Fabrication and validation of an organonchip system with. Importantly, this lungonachip model provides new opportunities to reconstitute organlevel physiological functions that arise from complex interplay between. Reconstitution and direct visualization of complex organ level responses involved in pulmonary inflammation and infection in the lung onachip device. Furthermore, a body on a chip, integrating multi organ functions on a microfluidic device, has also been proposed for prediction of organ interactions. Development of a functional glomerulus at the organ level on a chip to mimic hypertensive nephropathy. Fabrication and validation of an organ on chip system with integrated electrodes to directly quantify transendothelial electrical resistance marinke w. Reconstituting organ level lung functions on a chip this copy is for your personal, noncommercial use only. Bioprinting a 3d vascular construct for engineering a vessel.
Modelling cancer in microfluidic human organsonchips. Dec 26, 2019 the organ on a chip model mimics the structural and functional features of human tissues or organs and has great importance in translational research. Though most lung cancer starts in the lungs, some cases start in other parts of the body and spread to the lungs. Chip reconstituting organlevel lung functions on a. Within the alveolus, the alveolar type ii at2 epithelial cell is particularly important because it has the specialized function of surfactant production and also serves as a resident stem cell that proliferates in response to injury and subsequently differentiates into alveolar type i at1. Reconstituting organ level lung functions on a chip. One of these parameters is mechanical force, which imparts strain on cells and tissues and is an integral part of the environment that modulates the cellular phenotype.
Recent advances in organonachip systems have led to. Dec 21, 2015 the small airway on a chip allows the recapitulation of human lung pathophysiology in vitro and analysis of responses to drugs. Download citation reconstituting organlevel lung functions on a chip here, we describe a biomimetic microsystem that reconstitutes the critical functional. Mechanically active organonachip microdevices that reconstitute tissuetissue interfaces critical to organ function may therefore expand the capabilities of cell culture models and provide lowcost alternatives to animal and clinical. Lungonachip technologies for disease modeling and drug. Importantly, this lung on a chip model provides new opportunities to reconstitute organ level physiological functions that arise from complex interplay between multiple tissue types in the living human lung. By integrating living human cells with synthetically generated yet physiologically relevant microenvironments, organs on a chip can mimic integrated organ level functions necessary for physiological homeostasis, as well as complex disease processes 15, 16. Toward a more reliable output, huh and colleagues developed a lungonachip that models human lung function in both normal and disease states. To date, most focus has been on devices specifically designed to culture just one functional unit of a specific organ. The bioartificial lung must perform adequately and remain viable after implantation when the scaffold is seeded with the appropriate types of cells in sufficient numbers. Reconstituting organlevel lung functions on a chip researchgate. Matthews,2,3 akiko mammoto,2 martin montoyazavala,1,2 hong yuan hsin,2 donald e.
A the lung chip is made of an optically clear, flexible, silicone rubber polymer the size of a computer memory stick with two tiny hollow channels running parallel along its length separated by a flexible porous membrane of the same material channels are filled with blue and yellow dyes. In this optic, new data analysis algorithms have to be developed in order to extract novel features of cell behavior and cellcell interactions. Hsin h y and ingber d e 2010 reconstituting organlevel lung functions on a. Chip reconstituting organlevel lung functions on a this copy is for your personal, noncommercial use only. Hsin h y and ingber d e 2010 reconstituting organlevel lung functions on. A human breathing lungonachip annals of the american. Development of a functional glomerulus at the organ level. Similarly to the lung on chip, using microfluidic chips for this application proved to be very important since it allowed to recreate the mechanical tension, simulating peristaltic movement. Organsonchips can overcome this limitation and better mimic in. Oct 10, 2017 here, we show that microfluidic organ on a chip organ chip cell culture technology can be used to create in vitro human orthotopic models of nonsmallcell lung cancer nsclc that recapitulate organ microenvironmentspecific cancer growth, tumor dormancy, and responses to tyrosine kinase inhibitor tki therapy observed in human patients in vivo. The emergence of microphysiological systems organsonchips.
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