Reconstituting organlevel lung functions on a chip science. The small airwayona chip allows the recapitulation of human lung pathophysiology in vitro and analysis of responses to drugs. Small airwayonachip enables analysis of human lung. Lung ona chip technologies for disease modeling and drug development supplementary issue. We demonstrate the first reported deposition of aerosol into a microfluidic channel using a commercial nebulizer as a source of aerosol. However, current lung ona chip platforms are primarily monolayer epithelialendothelial cocultures, separated by a thin membrane, lacking microvasculaturenetworks or interstitialfibroblasts. Dec 27, 20 il2 induced pulmonary edema is modeled in a microengineered lung on a chip that reproduces the lung microarchitechture and breathing induced cyclic mechanical distortion of the alveolar capillary interface. Jun 25, 2010 the lung ona chip simulates this membrane. Jul 08, 2015 imagine, says ingber, introducing a drug to the lung chip and seeing how it affects the kidney chip.
In 20, the same group presented a followup paper 5. Secondgeneration lungonachip with an array of stretchable. Here we describe a microphysiological system that replicates the functional unit of the living human lung. Their strategic integration can address each approachs limitations and provide a path toward a superior, synergistic strategy of constructing tissues that will truly deliver on the promise of regenerative and precision medicine. A functional lung ona chip to study the physiology of the lung. The lung cells on the chip are grown on flexible, stretchable membranes which are a realistic imitation of the. May 29, 2020 the wyss institute at harvard university has been a worldwide pioneer in the development of in vitro organona chip, and the lung ona chip they developed was the first in the world huh et al. New organonachip designed to model influenza virus. The microdiaphragm used to stretch the alveolar barrier is inspired by the in vivo diaphragm, the main muscle respon.
Bernese researchers develop a second generation lungonchip. The microdiaphragm used to stretch the alveolar barrier is inspired by the in. Auxiliary vacuum channels enable stretching of the membrane to simulate breathing. Science translational medicine 4, 159ra147159ra147 2012. Dec 21, 2015 the small airwayona chip allows the recapitulation of human lung pathophysiology in vitro and analysis of responses to drugs. Human organ chip models recapitulate orthotopic lung. Combining microfabrication techniques with modern tissue engineering, lung ona chip offers a new in vitro approach to drug screening by mimicking the complicated mechanical and biochemical behaviors of a human lung. We report a lung ona chip array that mimics the pulmonary parenchymal environment, including the thin alveolar barrier and the threedimensional cyclic strain induced by breathing movements.
The printing process we report here is versatile enough to be adapted for multiple organona chip models beyond what is studied here. Need for alternative testing methods and opportunities for organona chip systems 2. Dec 01, 2019 microfluidic model of human lung ona chip design and fabrication. Lung ona chip has been developed to study complex human lung physiology and pathology in an organspecific context. In 2010, the first lung ona chip system was presented by d. Use of 3d organoids and lungonachip methods to study. Part i organona chip platforms to model disease pathogenesis 4. Pdf animal and twodimensional cell culture models have had a profound impact on not only lung research but also medical research at. Principal stresses and flow in the lung ona chip microdevice at t7 s due to an applied 0. I think it should be useful in testing the safety of different substances on the lung and i can also imagine other related applications, such as in research into how the lung functions. A rapidly prototyped lungonachip model using 3dprinted.
Flat and microstructured polymeric membranes in organson. Our model employs the comsol software capabilities. The lung ona chip is a complex, threedimensional model of a living, breathing human lung on a microchip. Sep 01, 2015 to mimic more physiologic conditions or evaluate celltocell interaction, two cell types should be used like lung ona chip, which has cultured endothelial cells on the bottom channels and alveolar cells on the top channels. Multiorgan on a chip for personalized precision medicine. A lungonachip array with an integrated bioinspired. This extended version of the video includes our findings when we mimicked pulmonary edema on the chip. Such a relation enables the development of the vacuum pressure waveform required to achieve a given membrane strain waveform during device. We have developed a comsol multiphysics software model of the lungona chip device of huh et al. The chip is vacuum prefilled with buffer solution, and the inlet channel is protected with a polymer seal that has to be removed shortly befor e application of the blood sample. Malhotra, sowmya viswanathan, venkatesan renugopalakrishnan, d. This human breathing lung onachip microdevice provides unique capabilities to reconstitute threedimensional microarchitecture, dynamic mechanical activity, and integrated physiological function of the alveolarcapillary interface.
In a human lung a, oxygen from the air is inhaled and travels to the lung s air sacs alveoli. 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. The lung ona chip microfluidic device is useful for investigating the role of ecp in airway remodelling e. Use of 3d organoids and lungonachip methods to study lung. Microfluidic model of human lung ona chip design and fabrication. Blood vessel cells endothelial and lung cells epithelial line opposite sides of a. Fabrication of a lungonchip microfluidic device suited for. Image and video acquisition and processing for clinical applications dipasri konar, mahesh devarasetty, didem v. It utilizes a porous, flexible rubbery matrix, with lung cells on one side and blood vessel cells on the other.
We reproduces some results from their 20 followup paper 5 in figure 1. The lung model discussed here consists of a three layer microfluidic device constructed entirely of polydimethylsiloxane pdms polymer. C 3d printer was used to fabricate the open well design of the chip model with upper and lower layers to recapitulate human lung. The lung ona chip model shown in figure 1 is based on huh et al. A a conceptual schematic of the experimental setup showing the human respiratory system b a crosssection of human airway tissue. Ecp plays a major role in attracting fibrocytes from blood vessels to airways. The product is a stunning achievement, and it is part of a growing abundance of bionic technology which combines natural biology and modern engineering with potentially revolutionary consequences. New organonachip designed to model influenza virus infections. Multiorgan on a chip for personalized precision medicine volume 8 issue 3 vivekanandan palaninathan, vimal kumar, toru maekawa, dorian liepmann, ramasamy paulmurugan, jairam r. In nanotoxicology studies, this lung mimic revealed that cyclic mechanical strain accentuates toxic and. The pioneering lung ona chip in 2010, huh demonstrated a pioneering microfluidic device that has since defined the direction of lung ona chip platforms huh et al.
Lung ona chip technologies for disease modeling and drug development. Advances in pulmonary therapy and drug development. Human organs on chips organ chips are microfluidic cell culture devices with separate. The device mimics the most active part of the lung, the boundary between the air sac and the bloodstream.
Living, breathing human lungonachip harvard gazette. Especially for chronic exposure, testing the effort required for manual manipulations can. These micro devices are translucent, they provide a window to watch inner workings of human organs. A human disease model of drug toxicityinduced pulmonary. Jun 24, 2010 wyss researchers have combined microfabrication techniques from the computer industry with modern tissue engineering techniques, human cells and a plain old vacuum pump to create a living, breathing human lung ona chip. The top portion is the air portion is the alveolar space and the bottom portion is the liquid called vascular channel.
Organsonachip ooac is a disruptive technology with widely recognized potential. Importantly, this lung ona chip model provides new opportunities to reconstitute organlevel physiological functions that arise from complex interplay between multiple tissue types in the living human lung. It is entirely based on polydimethylsiloxane pdms material, with an upper and a lower layer of channels separated by a porous. Researchers will use the technology to identify new drug targets and therapies. Using blood or urine we are able to derive induced pluripotent stem cells which in turn. Arrows denote velocity of culture medium lower channel, perfusion flow rate. This lung ona chip also introduced human neutrophils with culture media to the bottom channels to observe the movement. To develop this microengineered lung model, we used soft lithography. Lungonachip technologies for disease modeling and drug. Here, we focus on the respiratory system and provide an overview of these in vitro models which can be derived from primary lung cells, pluripotent stem cells, as well as healthy or diseased lungs. Researchers at the wyss institute for biologically inspired engineering at harvard university will use funding from the national institutes of health nih to develop clinically relevant in vitro models of influenza infection in the human lung based on their human organona chip organ chip microfluidic cell. Pdf recently, organonachip models, which are microfluidic devices that mimic the. The device reproduced respiratory motion through a vacuum leading to mechanical stretching and the formation of an alveolarcapillary barrier.
Researchers from the wyss institute for biologically inspired engineering at harvard university, harvard medical school and childrens hospital boston have c. Lung ona chip platforms for modeling disease pathogenesis 5. There, the oxygen is exchanged with carbon dioxide from the blood bloodair barrier, and the carbon dioxide is exhaled. Jun 24, 2010 organson chips this lung ona chip is neat and merges a number of technologies in an innovative way, says robert langer, mit institute professor. Biomedical engineering and c omputational biology 2016. A human breathing lungonachip annals of the american. The glass chip is placed in a plastic holder to facilitate han dling. Cell sources and methods for producing organotypic in vitro human tissue models 3. Sep 20, 2018 recent papers have highlighted the use of threedimensional 3d organoids and organsona chip to mimic tissue morphogenesis and function in vitro. The microdevice consists of a flexible membrane separating chambers for air and blood. Each organchip, such as the lung, liver, intestine or.
Oct 26, 2018 using a chip that integrates this muscle tissue, the researchers aim to measure how drugs targeted against one tissue, such as inhaled asthma drugs that target the lungs, affect the other tissues. Researchers create living lung on a chip new atlas. A rapidly prototyped lungonachip model using 3dprinted molds. Jun 25, 2010 here, we describe a biomimetic microsystem that reconstitutes the critical functional alveolarcapillary interface of the human lung. This bioinspired microdevice reproduces complex integrated organlevel responses to bacteria and inflammatory cytokines introduced into the alveolar space. In the lung ona chip, this second tube was made to mimic air whereas in the intestineona chip it represented the gut lumen. Simulation of nanoparticle transport and adsorption in a. Here we describe the development of a human lung small airwayona. Tyler nelson and others published lung ona chip find, read and cite all the research you need on researchgate. It can be used to test the effects of environmental toxins, absorption of aerosolized therapeutics, and. A 96well format microvascularized human lungonachip.
Pdf lungonachip technologies for disease modeling and. Flow control for organonachip application bronkhorst. The image on the left shows a crosssection of an airway in a healthy lung. Development of organoids and microfluidic on chip models has enabled studies of organlevel disease pathophysiologies in vitro. It is a multichannel 3d micro fluidic cell culture chip which simulates the activities, mechanisms, physiological response of entire organs.
Research on lungonachip indeed provides biomimetic microsystems that assist to assess. 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. We have developed a comsol multiphysics software model of the lung ona chip device of huh et al. This human breathing lung onachip microdevice provides unique capabilities to reconstitute threedimensional microarchitecture, dynamic mechanical activity, and integrated physiological fun. A human disease model of drug toxicityinduced pulmonary edema in a lung ona chip microdevice. After a first successful lung on chip system exhibiting essential features of the lung, the organson chip ooc technologies. Nov 07, 2012 the lung ona chip device, which the team first described only two years ago, is a crystal clear, flexible polymer about the size of a memory stick that contains hollow channels fabricated using.
Small airwayona chip enables analysis of human lung inflammation and drug responses in vitro. Typical alveolar epithelial cell markers are expressed, while the barrier properties are preserved for up to 3 weeks. Vacuum channels flank the midsection, which consists of an upper channel for air or cell culture medium and a lower channel for blood or cell culture medium. A human disease model of drug toxicityinduced pulmonary edema in a lung ona chip microdevice sci transl med. Here we will discuss the innovative design features included and a brief description of how it was used to study lung behavior.
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