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reported a multi-throughput multi-organ-on-a-chip system formed on a pneumatic pressure-driven medium circulation platform that was microplate-sized (Fig. Adv Drug Deliv Rev. Shear stress causes nephrotoxicity. In the case of long-term repeated administration or on-chip studies, the biomarkers identified in vitro may not fully reflect the in vivo equivalent. J Ind Eng Chem. Organ-on-a-chip systems that need to be mechanically stable can use thermoplastics such as polystyrene. Due to species differences, animal experiments often fail to replicate human experiments [23], and due to both high costs and ethical issues, the use of animals as models for drug testing has come under scrutiny [24]. Despite all advantages, this technique also has limitations. By compartmentalizing the channels, air can be introduced to the epithelial section to form an air-liquid interface that represents the lining of the alveolar air space. Skardal A, Murphy SV, Devarasetty M, Mead I, Kang H-W, Seol Y-J, Shrike Zhang Y, Shin S-R, Zhao L, Aleman J, et al. Wagner I, Materne E-M, Brincker S, Sssbier U, Frdrich C, Busek M, Sonntag F, Sakharov DA, Trushkin EV, Tonevitsky AG, et al. Polydimethylsiloxane (PDMS) is often used because it has tunable elastic properties, low cost, low autofluorescence, biocompatibility, optical clarity, and easy moldability [8]. In another study, a multiorgan microfluidic chip comprised of four organs, lung, brain, liver, and bone was developed to study the metastasis of primary lung cancer (Xu et al., 2016). 2018;3:1700200. https://doi.org/10.1002/admt.201700200. developed a polyurethane with similar properties to PDMS but with less absorption of hydrophobic compounds [91]. Oral drugs have to transverse the small intestine to enter the bloodstream. Nature. More suitable sensors are thus required. [49] developed a cell system to monitor cells in a 3D microfluidic setting. PubMedGoogle Scholar. Yang PC, Qi Y, Zhang DH. The model utilized vascular endothelial cells to form vascular networks and CMs were added to the vascular network gap. Grosberg A, Nesmith AP, Goss JA, Brigham MD, McCain ML, Parker KK. The figure illustrates the advantages (white) and limitations (black) of ESCs, ASCs, iPSCs, primordial and tissue biopsies, and cell lines in OOC devices. Adv Drug Deliv Rev. https://doi.org/10.1016/j.gde.2015.07.007. Physiologically relevant organs on chips (pages 1627). J Vis Exp Jove. The bone marrow-on-a-chip system is an extension to the Organ-on-a-chip approach. By combining hematopoietic stem and progenitor cells and bone marrow microenvironment, including mesenchymal stromal cells, this bone marrow model enables scientists to produce a functional BME and hematopoietic niche, as well as recreate trabecular bone models that are similar to physiological human bone (Torisawa et al., 2014). The sensing component for detecting and compiling data can be an embedded sensing output component or a transparent chip based visual function evaluation system. It is commonly used to precisely control microfluidic (109 to 1018 L) fluids using channels that range in size from tens to hundreds of microns and is known as a lab-on-a-chip [1,2,3,4]. The experimental system was suitable for both single muscle membrane measurements and high-throughput automated multi-plate assays. Molecules. 2013;340:11904. Lab Chip. https://doi.org/10.1039/b907515a. Micromachines (Basel). [104] were the first to combine liver and intestines in a microfluidic device. Lee PJ, Hung PJ, Lee LP. Zhou Q, Patel D, Kwa T, Haque A, Matharu Z, Stybayeva G, Gao Y, Diehl AM, Revzin A. Liver injury-on-a-chip: microfluidic co-cultures with integrated biosensors for monitoring liver cell signaling during injury. Tzatzalos E, Abilez OJ, Shukla P, Wu JC. 2018;22:31024. The high failure rate during the drug testing process is partially due to the fact that animal models are not always predictive of the human condition. 2017;114:18494. Peng J, Rochow N, Dabaghi M, Bozanovic R, Jansen J, Predescu D, DeFrance B, Lee SY, Fusch G, Ravi Selvaganapathy P, et al. Wang YI, Abaci HE, Shuler ML. (reprinted with permission from [85] Copyright 2016, Royal Society of Chemistry), 3D heart-on-a-chip. showed that CXCL12 acts on the CXCR4 receptor on the vascular endothelium suggesting that CXCL12 can act independently of its receptors CXCR4 or CXCR7 on the cancer cells. The intestine and liver slices functioned on the chip and demonstrated its applicability to organ interactions including the regulation of bile acid synthesis. Ma et al. This permitted more in-depth physiological studies of the epithelial barrier. The most common types include embryonic stem cells (ESCs), induced pluripotent stem cells (iPSCs), and adult stem cells (ASCs). Privacy However, in view of the very human nature of our immune system, which is involved in the evolution and progression of basically every disease, development of drugs for nearly all diseases may benefit from the organ-on-a-chip approach when based on stem cells from patients with the disease of interest, as will be discussed next. https://doi.org/10.1103/RevModPhys.77.977. Others not discussed in this review include blood vessels [99, 114, 115], the skin [116, 117], the BBB [118, 119], skeletal muscle [120, 121], and the CNS [122, 123]. 2014;239:124054. The advantage of 3D printing is to allow user-defined digital masks to provide versatility in cell patterns, critical for the in vitro reconstruction of the cellular microenvironment. [61] used their system to analyze viral replication of the hepatitis B virus. The organ-on-a-chip (OOAC) is in the list of top 10 emerging technologies and refers to a physiological organ biomimetic system built on a microfluidic chip. The hepatic microvascular system in health and its response to toxicants. Yang X, Li K, Zhang X, Liu C, Guo B, Wen W, Gao X. Nanofiber membrane supported lung-on-a-chip microdevice for anti-cancer drug testing. The incorporation of microsensors enables the control of various parameters such as chemical conditions (pH, oxygen supply) and physical conditions (fluidic shear stress) by changing the flow rate or channel dimensions (Bhatia and Ingber, 2014). These novel techniques simulated the hepatic lobule structure. 2017;4:148. https://doi.org/10.3389/fmed.2017.00148. https://doi.org/10.1126/science.1188302. 2007;7:1094110. In 2015, Stucki et al. Galie PA, Nguyen DHT, Choi CK, Cohen DM, Janmey PA, Chen CS. A human proximal tubule-on-a-chip to study renal disease and toxicity. Although the multi-organs-on-a-chip concept remains in its infancy, major breakthroughs have been made, including the design of two-organs [104, 105], three-organs [106, 107], four-organs [108, 109], and ten organs on the chip [110]. 2015;112:257182. News-Medical.Net provides this medical information service in accordance https://doi.org/10.1039/c7lc01224a. Anal Chem. [56] produced a biomimetic platform for the perfusion of hepatic spheroids in situ. 2017. https://doi.org/10.3390/bioengineering4020046. Development of an enhanced human gastrointestinal epithelial culture system to facilitate patient-based assays. Huh et al. In 2013, the same microfluidic device was used to culture human primary renal epithelial cells [75]. Organs such as the brain and the immune system are very typically human. 2005;77:9771026. Integr Biol (Camb). 2) [64] using soft lithography to divide the chip into regions separated by 10m PDMS membranes with an extracellular matrix (ECM). Vandussen KL, Marinshaw JM, Nurmohammad S, Hiroyuki M, Clara M, Tarr PI, Ciorba MA, Stappenbeck TS. A dynamic multi-organ-chip for long-term cultivation and substance testing proven by 3D human liver and skin tissue co-culture. Ho CT, Lin RZ, Chen RJ, Chin CK, Gong SE, Chang HY, Peng HL, Hsu L, Yew TR, Chang SF. In a nutshell, the microfluidic system contains two microchannels separated by a porous membrane. https://doi.org/10.1039/c0lc00273a. Peel S, Corrigan AM, Ehrhardt B, Jang K-J, Caetano-Pinto P, Boeckeler M, Rubins JE, Kodella K, Petropolis DB, Ronxhi J, et al. Gas exchange in the lungs is regulated by the alveoli which can be challenging to reproduce in vitro. Adv Mater Technol. A strategy for integrating essential three-dimensional microphysiological systems of human organs for realistic anticancer drug screening. 2018. https://doi.org/10.3390/bioengineering5030056. Jang KJ, Cho HS, Kang DH, Bae WG, Kwon TH, Suh KY. Fluid-shear-stress-induced translocation of aquaporin-2 and reorganization of actin cytoskeleton in renal tubular epithelial cells. 2008;30:81121. Mandenius C-F. Microfluidic devices only require micro-scale volumes of cell and drug samples. Jalili-Firoozinezhad S, Gazzaniga FS, Calamari EL, Camacho DM, Fadel CW, Bein A, Swenor B, Nestor B, Cronce MJ, Tovaglieri A, et al. Polystyrene has also been used for organ-on-a-chip technology, though it is rigid and may not be suitable for every design [92]. Zhang YS, Arneri A, Bersini S, Shin S-R, Zhu K, Goli-Malekabadi Z, Aleman J, Colosi C, Busignani F, DellErba V, et al. have shown that human skin equivalents, human ex vivo skin, and hair follicle cultures all had increased longevity in the organ-on-chip, as compared with static 3-D cultures [21]. Shin W, Hinojosa CD, Ingber DE, Kim HJ. Small airway-on-a-chip enables analysis of human lung inflammation and drug responses in vitro. d Media circulation was performed using pneumatic pressure in the two-organ system. Further characterization of cultured cytoplasm in metabolomics, proteomics, genomics, and epigenomic analysis will help improve the functional outcome of these studies. https://doi.org/10.1021/acsami.5b05978. Lab Chip. (reprinted with permission from [52] Copyright 2006, Royal Society of Chemistry), Schematic of the DLM-based liver tumor-on-a-chip. Materials such as PLGA and polydioxanone (PDO) are thus used. https://doi.org/10.1039/c8lc00852c. The chip represented a preclinical assessment of drug cardiac efficacy. Front. Likewise, the heart-on-a-chip was fabricated to measure the structure-function relationships between the replicated hierarchical tissue architectures of laminar cardiac muscle. Surface modifications [41], templates [42], and 3D printing [43] contribute to cell patterning on the chip. In this interview, News-Medical talks to Dr. Shuang Zhou about cytokine-base cancer immunotherapy, the current state of the field, and future prospects. Wnorowski A, Yang H, Wu JC. 2019;24:121723. Proc Natl Acad Sci USA. Blume et al. Zhou J, Khodakov DA, Ellis AV, Voelcker NH. Human induced pluripotent stem cells and their use in drug discovery for toxicity testing. 2010;10:3642. Song JW, Daubriac J, Tse JM, Bazou D, Munn LL. More expensive components should be reusable. Audron V. Kalvelyt, Aurimas Stulpinas, in Advances in Molecular Toxicology, 2017. Villi are key to absorption and their morphology must be maintained on the chip [88]. designed the first liver based system that consisted of microfluidic pores in which 3T3-J2 fibroblasts and rat liver cells were co-cultured to mimic an airway interface (Fig. https://doi.org/10.1039/b901377f. Thus, a material for manufacturing in vitro therapeutic testing systems needs to be low-cost, easy to obtain, easy to process, and processed with replicability. Nonetheless, there have been recent developments in the ability to connect multiple organ-on-a-chip models to analyze the effects of drug toxicity in the surrounding tissues of the target organ. Microscale 3-D hydrogel scaffold for biomimetic gastrointestinal (GI) tract model. 3b) in organ culture devices. Lab Chip. Peel et al. Cookies policy. [113] produced an innovative combination of laser technologies. MRC. They have a great potential in fundamental research and in the pharmaceutical industry. Reconstituting organ-level lung functions on a chip. Yildirimer L, Zhang Q, Kuang S, Cheung C-WJ, Chu KA, He Y, Yang M, Zhao X. Furthermore, Song et al. 2016. https://doi.org/10.3390/molecules21091128. Retrieved on July 20, 2022 from https://www.news-medical.net/life-sciences/What-is-Organ-on-a-Chip-(OOC).aspx. [78] designed stable tubule culture systems that permitted extended expansion and human kidney tissue analysis. 2015;10:3945. In addition, drug development and toxicology require the assessment of the physiological effects of thousands of compounds [19]. Multilineage potential of adult human mesenchymal stem cells. The membranes can, therefore, form an interface for the cellular cross talk of endothelial and epithelial cell layers. Chip-based human liver-intestine and liver-skin co-culturesA first step toward systemic repeated dose substance testing in vitro. Maschmeyer I, Hasenberg T, Jaenicke A, Lindner M, Lorenz AK, Zech J, Garbe L-A, Sonntag F, Hayden P, Ayehunie S, et al. Studies, bottlenecks and challenges of microarray of micro organs. An organ-on-a-chip is a micro-scale system used for mimicking the human body environment. Most critically, as the number of organs on the chip increases, functionality becomes more complex and generated data carry artefactual and non-translatable risks. Schneider [86] designed convenient and efficient chips to generate heart tissue in a controlled environment based on human induced pluripotent stem cells. Genome fidelity was low, so the chips mimicked intestinal function. 2019. https://doi.org/10.1038/s41551-019-0397-0. In the above BBB-on-a-chip procedures, previously unknown metabolic coupling between BBB and neurons was discovered. Various studies show that the same cells cultured under 2D or 3D conditions differ in their morphological and physiological characteristics, leading to a different cellular response [177,178]. The authors declare that they have no competing interests. a Preparation of the DLM solution from a natural liver; b 3D schematic representation of the various components of the equipment (top and bottom, top and bottom microchannels, PET membrane, air inlet, and outlet) and their respective dimensions. 2014;14:20339. The lung-on-a-chip was developed to mimic the key structural, functional and mechanical properties of the human alveolar-capillary interface. 2016;6:2686373. b Organ-on-a-chip techniques can mimic real-life in vivo states. With the models of human asthmatic and chronic obstructive pulmonary disease airways, therapeutics were tested and the chip model recapitulated in vivo responses to a similar therapy. Stoakes, Shelley Farrar. These range from autoimmune diseases all the way to cancer. Polymers (Basel). Intestinal cells were cultured alone or with endothelial cells including HUVECs [91]. Mol Ther. Jang K-J, Mehr AP, Hamilton GA, Mcpartlin LA, Chung S, Suh K-Y, Ingber DE. Inflammatory stimuli were introduced into the system through neutrophils that were passed to the fluid channels. [60] developed biomimetic liver tumors through integrating decellularized liver matrixes (DLM) with gelatin methacryloyl (GelMA) to mirror the 3D tumor microenvironment (TME). 1) [52]. Micromachines (Basel). However, cell lines do not represent normal physiological conditions and primary cell culture time is limited, and the quality is unstable. [69] produced a poly(lactic-co-glycolic acid) (PLGA) electrospinning nanofiber membrane as a chip matrix for cell scaffolds. Nature. 4) that mimicked the physiological and mechanical environment of CMs. PDMS is the most widely employed material, but comes with disadvantages as the resultant film is thicker than the in vivo morphology. This method combines a polyvinyl acetate coating, carbon dioxide laser ablation, and continuous cell seeding techniques on a glass chip. OOAC has broad applications in precision medicine and biological defense strategies. Moreover, some culture platforms, especially for multiorgan culture, include biosensing elements to permit continuous screening of organoids behavior that will minimize the variability. 2013;13:695705. News-Medical. Together, these studies strongly support the use of this system to recapitulate metastatic BME. Kim et al. Sung JH, Yu J, Luo D, Shuler ML, March JC. Comparison of human induced pluripotent and embryonic stem cells: fraternal or identical twins? 1995;75:51960. Zhou et al. Bioengineering (Basel). Marsano et al. [84] introduced the heart-on-a-chip device that used high-speed impedance detection to assess cardiac drug efficacy. [82] utilized hydrogels to produce self-assembled myocardial sheets in a PDMS model. Science. 2018. https://doi.org/10.3390/genes9020114. Red arrows indicate the direction of media flow. Biomicrofluidics. Most organs-on-a-chip developed at present mimic one particular organ level function only. When the multisensor platform is developed, drug discovery, pharmacodynamic studies, and preclinical drug testing including patient-derived personal models will allow predicting the toxicity and the outcome of the treatment more accurately [350]. In 2010, Van et al. Alexander FA, Eggert S, Wiest J. Skin-on-a-chip: transepithelial electrical resistance and extracellular acidification measurements through an automated air-liquid interface. This permeable endothelial gap separated hepatocytes in cord-based structures permitting their separation from the external sinusoidal region, simultaneously maintaining efficient substance exchange. Wevers NR, Kasi DG, Gray T, Wilschut KJ, Smith B, van Vught R, Shimizu F, Sano Y, Kanda T, Marsh G, et al. 2018;8:992. https://doi.org/10.3390/app8060992. Exp Cell Res. Yum et al. She is passionate about science communication with a particular focus on reporting the latest science news and discoveries to a broad audience. The hepatic system is the major site of drug/toxin metabolism. Huh D, Matthews BD, Mammoto A, Montoya-Zavala M, Hsin HY, Ingber DE. Fundamentals of microfluidic cell culture in controlled microenvironments. [57] produced systems to study how hepatocytes affect other cell types. Different signal stimuli can be derived from for drug screening approaches [47]. BioEssays. Chin J Tissue Eng Res. By continuing to browse this site you agree to our use of cookies. produced bionic devices (Fig. Sosa-Hernndez JE, Villalba-Rodrguez AM, Romero-Castillo KD, Aguilar-Aguila-Isaas MA, Garca-Reyes IE, Hernndez-Antonio A, Ahmed I, Sharma A, Parra-Saldvar R, Iqbal HMN. The application of electrodes causes the contraction of myocytes (muscle cells) leading to the finding of a relationship between tissue stress and the radius of curvature produced in the muscular thin films during contraction. 2019;54:788392. Marx U, Walles H, Hoffmann S, Lindner G, Horland R, Sonntag F, Klotzbach U, Sakharov D, Tonevitsky A, Lauster R. Human-on-a-chip developments: a translational cutting-edge alternative to systemic safety assessment and efficiency evaluation of substances in laboratory animals and man? Engineered heart tissues and induced pluripotent stem cells: macro- and microstructures for disease modeling, drug screening, and translational studies. https://doi.org/10.1002/bit.26087. 2013;34:581320. Tsamandouras N, Wen LKC, Edington CD, Stokes CL, Griffith LG, Cirit M. Integrated gut and liver microphysiological systems for quantitative in vitro pharmacokinetic studies. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. 2018;48:4752. 8) [133]. 2015;15:446778. 2015;34:5460. 2018;18:48695. Multi-tissue interactions in an integrated three-tissue organ-on-a-chip platform. Zhang J, Wei X, Zeng R, Xu F, Li X. The microenvironment of the intestine was reconstructed through shear force and cyclic strains. The multi-organ-on-a-chip, otherwise referred to as the human-on-a-chip [98] simultaneously constructs multiple organs attracting obvious research attention. This platform represents an advance in the field and provides standard functional 3D heart models. https://doi.org/10.1021/ac051856v. Electrophoresis. By realizing different organ functions on a chip, organ-on-a-chip technology is a potentially useful for building models of such complex diseases. Toxicol Lett. A decreased absorbance of small hydrophobic molecules influences solvent efficacy and toxicity. These materials do not simulate extracellular matrix in animals and humans. Wang Y, Huang X, Shen Y, Hang R, Zhang X, Wang Y, Yao X, Tang B. Lab Chip. 2016;110:4559. e pressure quantitation. The device permitted the exploration of the etiology of intestinal disease and identified therapeutic targets and drugs. Contributions of microbiome and mechanical deformation to intestinal bacterial overgrowth and inflammation in a human gut-on-a-chip. Satoh et al. Li Y-C, Lin M-W, Yen M-H, Fan SM-Y, Wu J-T, Young T-H, Cheng J-Y, Lin S-J. Sci Rep. 2018;8:4530. https://doi.org/10.1038/s41598-018-22749-0. https://doi.org/10.1039/c7lc00952f. https://doi.org/10.1039/c3lc50234a. 1999;284:1437. https://doi.org/10.1039/c0lc00043d. 2012;4:46170. https://doi.org/10.5966/sctm.2015-0095. Although the 3D tissue structure more accurately simulates the in vivo situation compared to 2D models, due to the limitations of technology and cost and the assembly of extracellular matrix and the presetting and formation of vasculature, living cell in organ tissues are still mostly cultivated in 2D. Could Algae Solve the Global Climate Crisis? Its development has attracted worldwide research attention and great scientific advances have been made. Direct visualization and quantitative analysis was performed, which was not permitted in traditional cell culture or animal models. Article Upper layers are present in the culture chamber and the drive chambers represent the lower layers; d 3D illustration; e real-life chip; f SEM of the chip cross section. Biomicrofluidics. This is of great significance to our understanding of the dysfunction and pathogenesis of the body, and therefore closely aligns with the fields of medicine, drug development and toxicology [17]. [81] used PDMS to produce an elastic film with a surface texture and implanted neonatal rat CMs on the membrane to form a muscle membranes. Mccuskey RS. [72] used a microfluidic chip platform to mimic the microenvironment of lung cancer with cancer cell lines and primary cancer cells and tested different chemotherapeutic drugs. Sci Rep. 2019;9:1796. https://doi.org/10.1038/s41598-018-34828-3. These biomimetic, microfluidic devices are generally small in size and are being developed with increased complexity. https://doi.org/10.1039/c8lc00829a. This system holds value as a drug screening platform to identify compounds that produce systemic skin reactions. More specifically, each organ-on-a-chip is fabricated on a clear polymer containing hollow microfluidic channels lined with living human cells. The system included an alveolar barrier and 3D cyclic strain that mimicked respiration representing the first elastic membrane expansion model to simulate breathing. Qian T, Shusta EV, Palecek SP. Human organ culture: updating the approach to bridge the gap from in vitro to in vivo in inflammation, cancer, and stem cell biology. The ability of 3D cultures for intercellular and cellular matrix interactions affects signal transduction and gene expression. 2018;4(1):7889. Organ-on-a-chip devices can overcome the limitations of conventional two-dimensional cell culture methodologies, allowing for the establishment of models that mimic the three-dimensional arrangement of different cell types closer to the physiological condition. Bodily functions rely on the interaction and adaptation of many lower-level components such as tissues, cells, proteins and genes. The microchannel is small, but has a large surface area and high mass transfer, favoring its use in microfluidic technology applications including low regent usage, controllable volumes, fast mixing speeds, rapid responses, and precision control of physical and chemical properties [1, 5, 6]. Sci Rep. 2017;7:8837. https://doi.org/10.1038/s41598-017-08879-x. 2018;18:337992. Biofabrication. The chip was applicable for nephrotoxicity assessments, therapeutic development, regenerative medicine, and kidney development and disease. Such biosensors can give real-time continuous readout of the health of the system and the effectiveness of the drug. Interconnected microphysiological systems for quantitative biology and pharmacology studies. This produced a pathological model of pulmonary edema through the introduction of interleukin-2 (IL-2) [65]. A lung-on-a-chip array with an integrated bio-inspired respiration mechanism. Kim W, Kim J, Park H-S, Jeon JS. The principle of this technology is that multiple organoids of different cells may be organized together in a body-similar manner by the microfluidic connections. 2015;10:e0139872. In semi-static systems, the organs are joined via fluidic networks with Transwell-based [103] tissue inserts. Lantada et al. Lab Chip. https://doi.org/10.1039/c3lc41017j. Furthermore, microfluidic models have been successfully used to investigate angiogenesis and the metastatic cascade to bone (Bersini et al., 2014). The main advantage of such systems is the integration of sensors that would allow monitoring physical, biochemical, and optical parameters in situ in real time. Humayun M, Chow C-W, Young EWK. The myocardium is a major component of the heart. Organ-on-a-chip systems in the nearest future may represent the most advanced miniaturized multiorganoid model that is expected to become an intermediate link between cell models and a human body. 2009;9:138594. Visone R, Gilardi M, Marsano A, Rasponi M, Bersini S, Moretti M. Cardiac meets skeletal: whats new in microfluidic models for muscle tissue engineering. The formation of compartments inside the microfluidic device increases control of the microenvironment by confining cells. The structure of individual organ-on-chip systems varies because the arrangement of organ specific cell types within the microfluidic device is made to resemble the basic morphology of the organ. 2019. https://doi.org/10.3390/molecules24040675. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data. (Lausanne). 2019;19:41021. In this interview, we speak to Dr. David Field about his latest research into anxiety and depression and whether vitamin B6 supplements could help to reduce it. One of the main tasks in creating new models of a 3D cell culture is to ensure physiological relevance, high throughput, and reproducibility. This realistically simulates the lung environment. Biotechnol J. Xu Z, Gao Y, Hao Y, Li E, Wang Y, Zhang J, Wang W, Gao Z, Wang Q. Lee SH, Jun B-H. Advances in dynamic microphysiological organ-on-a-chip: design principle and its biomedical application. The lung-on-a-chip can also represent complex whole organ-level response, such as pulmonary inflammation, by the introduction of blood-borne immune cells to the fluid within the vascular channel. Sun X, Nunes SS. produced the first 3D hydrogel structure to simulate the human intestinal villi [90]. The system was combined with microenvironment cues and toxin exposure as a physiological model of chronic lung disease. Lab on a chip. Alpe N. State-of-the-art of 3D cultures (organs-on-a-chip) in safety testing and pathophysiology. This multi-organ model was used to study the complex biology and enterohepatic circulation of bile acids (Jin et al., 2018). 2019. https://doi.org/10.3390/polym11050792. The concept of large-diameter channels was achieved in the umbilical arteries and veins, providing LAD with high extra-corporeal blood flow. Design and fabrication of a liver-on-a-chip platform for convenient, highly efficient, and safe in situ perfusion culture of 3D hepatic spheroids. This chip represented the closest model to the living duodenum and reproduced key features of the small intestine. 2019;15:391406. Kim HJ, Huh D, Hamilton G, Ingber DE. For decades, traditional two-dimensional (2D) cell culture systems formed an important platform for life science research. Exp Biol Med (Maywood). In some cases, biodegradable materials are desired as scaffolds in the system. Lee H, Kim DS, Ha SK, Choi I, Lee JM, Sung JH. Organ-on-a-chip technology can also produce an optimal supply of nutrients and oxygen along with the efficient removal of catabolic metabolites. Mesenchymal stem cell preparationscomparing apples and oranges. Microfluidics, BioMEMS, and medical microsystems XV. Biomicrofluidics. Will we be able to create models of depression or schizophrenia in this type of model? Daz Lantada A, Pfleging W, Besser H, Guttmann M, Wissmann M, Plewa K, Smyrek P, Piotter V, Garca-Ruz JP. The emergence of microfluidics has enabled in vitro bionic studies of cardiac tissue. They are stiff materials with stable surface chemistries. Using 2D systems, the functions of various cells are studied by culturing cells or cell products. Peng et al. 2018;6:197. https://doi.org/10.3389/fbioe.2018.00197. 2018. https://doi.org/10.3390/mi9120671. 2015;15:268899.

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