Journal articles: 'Multi-organ-on-chip'

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Zuchowska, Agnieszka, and Sandra Skorupska. "Multi-organ-on-chip approach in cancer research." Organs-on-a-Chip 4 (December 2022): 100014. http://dx.doi.org/10.1016/j.ooc.2021.100014.

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

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

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Palaninathan, Vivekanandan, Vimal Kumar, Toru Maekawa, Dorian Liepmann, Ramasamy Paulmurugan, Jairam R. Eswara, Pulickel M. Ajayan, et al. "Multi-organ on a chip for personalized precision medicine." MRS Communications 8, no. 03 (August 13, 2018): 652–67. http://dx.doi.org/10.1557/mrc.2018.148.

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Kim, Jinyoung, Junghoon Kim, Yoonhee Jin, and Seung-Woo Cho. "In situ biosensing technologies for an organ-on-a-chip." Biofabrication 15, no. 4 (August 17, 2023): 042002. http://dx.doi.org/10.1088/1758-5090/aceaae.

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Abstract The in vitro simulation of organs resolves the accuracy, ethical, and cost challenges accompanying in vivo experiments. Organoids and organs-on-chips have been developed to model the in vitro, real-time biological and physiological features of organs. Numerous studies have deployed these systems to assess the in vitro, real-time responses of an organ to external stimuli. Particularly, organs-on-chips can be most efficiently employed in pharmaceutical drug development to predict the responses of organs before approving such drugs. Furthermore, multi-organ-on-a-chip systems facilitate the close representations of the in vivo environment. In this review, we discuss the biosensing technology that facilitates the in situ, real-time measurements of organ responses as readouts on organ-on-a-chip systems, including multi-organ models. Notably, a human-on-a-chip system integrated with automated multi-sensing will be established by further advancing the development of chips, as well as their assessment techniques.

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Vivas, Aisen, Albert van den Berg, Robert Passier, Mathieu Odijk, and Andries D. van der Meer. "Fluidic circuit board with modular sensor and valves enables stand-alone, tubeless microfluidic flow control in organs-on-chips." Lab on a Chip 22, no. 6 (2022): 1231–43. http://dx.doi.org/10.1039/d1lc00999k.

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Translational Organ-on-Chip Platform (TOP) is a multi-institutional effort to develop an open platform for automated organ-on-chip culture that actively facilitates the integration of components from various developers.

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Satoh, T., S. Sugiura, K. Shin, R. Onuki-Nagasaki, S. Ishida, K. Kikuchi, M. Kakiki, and T. Kanamori. "A multi-throughput multi-organ-on-a-chip system on a plate formatted pneumatic pressure-driven medium circulation platform." Lab on a Chip 18, no. 1 (2018): 115–25. http://dx.doi.org/10.1039/c7lc00952f.

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

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

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Loskill, Peter, Thiagarajan Sezhian, Kevin M. Tharp, Felipe T. Lee-Montiel, Shaheen Jeeawoody, Willie Mae Reese, Peter-James H. Zushin, Andreas Stahl, and Kevin E. Healy. "WAT-on-a-chip: a physiologically relevant microfluidic system incorporating white adipose tissue." Lab on a Chip 17, no. 9 (2017): 1645–54. http://dx.doi.org/10.1039/c6lc01590e.

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Zhao, Yi, Ranjith Kankala, Shi-Bin Wang, and Ai-Zheng Chen. "Multi-Organs-on-Chips: Towards Long-Term Biomedical Investigations." Molecules 24, no. 4 (February 14, 2019): 675. http://dx.doi.org/10.3390/molecules24040675.

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With advantageous features such as minimizing the cost, time, and sample size requirements, organ-on-a-chip (OOC) systems have garnered enormous interest from researchers for their ability for real-time monitoring of physical parameters by mimicking the in vivo microenvironment and the precise responses of xenobiotics, i.e., drug efficacy and toxicity over conventional two-dimensional (2D) and three-dimensional (3D) cell cultures, as well as animal models. Recent advancements of OOC systems have evidenced the fabrication of ‘multi-organ-on-chip’ (MOC) models, which connect separated organ chambers together to resemble an ideal pharmacokinetic and pharmacodynamic (PK-PD) model for monitoring the complex interactions between multiple organs and the resultant dynamic responses of multiple organs to pharmaceutical compounds. Numerous varieties of MOC systems have been proposed, mainly focusing on the construction of these multi-organ models, while there are only few studies on how to realize continual, automated, and stable testing, which still remains a significant challenge in the development process of MOCs. Herein, this review emphasizes the recent advancements in realizing long-term testing of MOCs to promote their capability for real-time monitoring of multi-organ interactions and chronic cellular reactions more accurately and steadily over the available chip models. Efforts in this field are still ongoing for better performance in the assessment of preclinical attributes for a new chemical entity. Further, we give a brief overview on the various biomedical applications of long-term testing in MOCs, including several proposed applications and their potential utilization in the future. Finally, we summarize with perspectives.

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Sun, Qiyue, Jianghua Pei, Qinyu Li, Kai Niu, and Xiaolin Wang. "Reusable Standardized Universal Interface Module (RSUIM) for Generic Organ-on-a-Chip Applications." Micromachines 10, no. 12 (December 5, 2019): 849. http://dx.doi.org/10.3390/mi10120849.

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The modular-based multi-organ-on-a-chip enables more stable and flexible configuration to better mimic the complex biological phenomena for versatile biomedical applications. However, the existing magnetic-based interconnection modes are mainly realized by directly embedding and/or fixing magnets into the modular microfluidic devices for single use only, which will inevitably increase the complexity and cost during the manufacturing process. Here, we present a novel design of a reusable standardized universal interface module (RSUIM), which is highly suitable for generic organ-on-chip applications and their integration into multi-organ systems. Both pasting-based and clamping-based interconnection modes are developed in a plug-and-play manner without fluidic leakage. Furthermore, due to the flexibility of the modular design, it is simple to integrate multiple assembled modular devices through parallel configuration into a high throughput platform. To test its effectiveness, experiments on the construction of both the microvascular network and vascularized tumor model are performed by using the integration of the generic vascularized organ-on-a-chip module and pasting-based RSUIM, and their quantitative analysis results on the reproducibility and anti-cancer drug screening validation are further performed. We believe that this RSUIM design will become a standard and critical accessory for a broad range of organ-on-a-chip applications and is easy for commercialization with low cost.

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Huang, Ngan F., Ovijit Chaudhuri, Patrick Cahan, Aijun Wang, Adam J. Engler, Yingxiao Wang, Sanjay Kumar, Ali Khademhosseini, and Song Li. "Multi-scale cellular engineering: From molecules to organ-on-a-chip." APL Bioengineering 4, no. 1 (March 1, 2020): 010906. http://dx.doi.org/10.1063/1.5129788.

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Goldstein, Yoel, Sarah Spitz, Keren Turjeman, Florian Selinger, Yechezkel Barenholz, Peter Ertl, Ofra Benny, and Danny Bavli. "Breaking the Third Wall: Implementing 3D-Printing Techniques to Expand the Complexity and Abilities of Multi-Organ-on-a-Chip Devices." Micromachines 12, no. 6 (May 28, 2021): 627. http://dx.doi.org/10.3390/mi12060627.

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The understanding that systemic context and tissue crosstalk are essential keys for bridging the gap between in vitro models and in vivo conditions led to a growing effort in the last decade to develop advanced multi-organ-on-a-chip devices. However, many of the proposed devices have failed to implement the means to allow for conditions tailored to each organ individually, a crucial aspect in cell functionality. Here, we present two 3D-print-based fabrication methods for a generic multi-organ-on-a-chip device: One with a PDMS microfluidic core unit and one based on 3D-printed units. The device was designed for culturing different tissues in separate compartments by integrating individual pairs of inlets and outlets, thus enabling tissue-specific perfusion rates that facilitate the generation of individual tissue-adapted perfusion profiles. The device allowed tissue crosstalk using microchannel configuration and permeable membranes used as barriers between individual cell culture compartments. Computational fluid dynamics (CFD) simulation confirmed the capability to generate significant differences in shear stress between the two individual culture compartments, each with a selective shear force. In addition, we provide preliminary findings that indicate the feasibility for biological compatibility for cell culture and long-term incubation in 3D-printed wells. Finally, we offer a cost-effective, accessible protocol enabling the design and fabrication of advanced multi-organ-on-a-chip devices.

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Sung, Jong Hwan. "Multi-organ-on-a-chip for pharmacokinetics and toxicokinetic study of drugs." Expert Opinion on Drug Metabolism & Toxicology 17, no. 8 (April 5, 2021): 969–86. http://dx.doi.org/10.1080/17425255.2021.1908996.

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Dehne, Eva-Maria, Tobias Hasenberg, Reyk Horland, and Uwe Marx. "Multi-organ on a chip: Human physiology-based assessment of liver toxicity." Toxicology Letters 280 (October 2017): S75. http://dx.doi.org/10.1016/j.toxlet.2017.07.192.

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Morais, Ana Sofia, Maria Mendes, Marta Agostinho Cordeiro, João J. Sousa, Alberto Canelas Pais, Silvia M. Mihăilă, and Carla Vitorino. "Organ-on-a-Chip: Ubi sumus? Fundamentals and Design Aspects." Pharmaceutics 16, no. 5 (May 2, 2024): 615. http://dx.doi.org/10.3390/pharmaceutics16050615.

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This review outlines the evolutionary journey from traditional two-dimensional (2D) cell culture to the revolutionary field of organ-on-a-chip technology. Organ-on-a-chip technology integrates microfluidic systems to mimic the complex physiological environments of human organs, surpassing the limitations of conventional 2D cultures. This evolution has opened new possibilities for understanding cell–cell interactions, cellular responses, drug screening, and disease modeling. However, the design and manufacture of microchips significantly influence their functionality, reliability, and applicability to different biomedical applications. Therefore, it is important to carefully consider design parameters, including the number of channels (single, double, or multi-channels), the channel shape, and the biological context. Simultaneously, the selection of appropriate materials compatible with the cells and fabrication methods optimize the chips’ capabilities for specific applications, mitigating some disadvantages associated with these systems. Furthermore, the success of organ-on-a-chip platforms greatly depends on the careful selection and utilization of cell resources. Advances in stem cell technology and tissue engineering have contributed to the availability of diverse cell sources, facilitating the development of more accurate and reliable organ-on-a-chip models. In conclusion, a holistic perspective of in vitro cellular modeling is provided, highlighting the integration of microfluidic technology and meticulous chip design, which play a pivotal role in replicating organ-specific microenvironments. At the same time, the sensible use of cell resources ensures the fidelity and applicability of these innovative platforms in several biomedical applications.

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Baert, Y., I. Ruetschle, W. Cools, A. Oehme, A. Lorenz, U. Marx, E. Goossens, and I. Maschmeyer. "A multi-organ-chip co-culture of liver and testis equivalents: a first step toward a systemic male reprotoxicity model." Human Reproduction 35, no. 5 (May 1, 2020): 1029–44. http://dx.doi.org/10.1093/humrep/deaa057.

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Abstract STUDY QUESTION Is it possible to co-culture and functionally link human liver and testis equivalents in the combined medium circuit of a multi-organ chip? SUMMARY ANSWER Multi-organ-chip co-cultures of human liver and testis equivalents were maintained at a steady-state for at least 1 week and the co-cultures reproduced specific natural and drug-induced liver–testis systemic interactions. WHAT IS KNOWN ALREADY Current benchtop reprotoxicity models typically do not include hepatic metabolism and interactions of the liver–testis axis. However, these are important to study the biotransformation of substances. STUDY DESIGN, SIZE, DURATION Testicular organoids derived from primary adult testicular cells and liver spheroids consisting of cultured HepaRG cells and hepatic stellate cells were loaded into separate culture compartments of each multi-organ-chip circuit for co-culture in liver spheroid-specific medium, testicular organoid-specific medium or a combined medium over a week. Additional multi-organ-chips (single) and well plates (static) were loaded only with testicular organoids or liver spheroids for comparison. Subsequently, the selected type of medium was supplemented with cyclophosphamide, an alkylating anti-neoplastic prodrug that has demonstrated germ cell toxicity after its bioactivation in the liver, and added to chip-based co-cultures to replicate a human liver–testis systemic interaction in vitro. Single chip-based testicular organoids were used as a control. Experiments were performed with three biological replicates unless otherwise stated. PARTICIPANTS/MATERIALS, SETTING, METHODS The metabolic activity was determined as glucose consumption and lactate production. The cell viability was measured as lactate dehydrogenase activity in the medium. Additionally, immunohistochemical and real-time quantitative PCR end-point analyses were performed for apoptosis, proliferation and cell-specific phenotypical and functional markers. The functionality of Sertoli and Leydig cells in testicular spheroids was specifically evaluated by measuring daily inhibin B and testosterone release, respectively. MAIN RESULTS AND THE ROLE OF CHANCE Co-culture in multi-organ chips with liver spheroid-specific medium better supported the metabolic activity of the cultured tissues compared to other media tested. The liver spheroids did not show significantly different behaviour during co-culture compared to that in single culture on multi-organ-chips. The testicular organoids also developed accordingly and produced higher inhibin B but lower testosterone levels than the static culture in plates with testicular organoid-specific medium. By comparison, testosterone secretion by testicular organoids cultured individually on multi-organ-chips reached a similar level as the static culture at Day 7. This suggests that the liver spheroids have metabolised the steroids in the co-cultures, a naturally occurring phenomenon. The addition of cyclophosphamide led to upregulation of specific cytochromes in liver spheroids and loss of germ cells in testicular organoids in the multi-organ-chip co-cultures but not in single-testis culture. LARGE-SCALE DATA N/A LIMITATIONS, REASONS FOR CAUTION The number of biological replicates included in this study was relatively small due to the limited availability of individual donor testes and the labour-intensive nature of multi-organ-chip co-cultures. Moreover, testicular organoids and liver spheroids are miniaturised organ equivalents that capture key features, but are still simplified versions of the native tissues. Also, it should be noted that only the prodrug cyclophosphamide was administered. The final concentration of the active metabolite was not measured. WIDER IMPLICATIONS OF THE FINDINGS This co-culture model responds to the request of setting up a specific tool that enables the testing of candidate reprotoxic substances with the possibility of human biotransformation. It further allows the inclusion of other human tissue equivalents for chemical risk assessment on the systemic level. STUDY FUNDING/COMPETING INTEREST(S) This work was supported by research grants from the Scientific Research Foundation Flanders (FWO), Universitair Ziekenhuis Brussel (scientific fund Willy Gepts) and the Vrije Universiteit Brussel. Y.B. is a postdoctoral fellow of the FWO. U.M. is founder, shareholder and CEO of TissUse GmbH, Berlin, Germany, a company commercializing the Multi-Organ-Chip platform systems used in the study. The other authors have no conflict of interest to declare.

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An, Fan, Yueyang Qu, Xianming Liu, Runtao Zhong, and Yong Luo. "Organ-on-a-Chip: New Platform for Biological Analysis." Analytical Chemistry Insights 10 (January 2015): ACI.S28905. http://dx.doi.org/10.4137/aci.s28905.

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Direct detection and analysis of biomolecules and cells in physiological microenvironment is urgently needed for fast evaluation of biology and pharmacy. The past several years have witnessed remarkable development opportunities in vitro organs and tissues models with multiple functions based on microfluidic devices, termed as “organ-on-a-chip”. Briefly speaking, it is a promising technology in rebuilding physiological functions of tissues and organs, featuring mammalian cell co-culture and artificial microenvironment created by microchannel networks. In this review, we summarized the advances in studies of heart-, vessel-, liver-, neuron-, kidney- and Multi-organs-on-a-chip, and discussed some noteworthy potential on-chip detection schemes.

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Giampetruzzi, Lucia, Amilcare Barca, Flavio Casino, Simonetta Capone, Tiziano Verri, Pietro Siciliano, and Luca Francioso. "Multi-Sensors Integration in a Human Gut-On-Chip Platform." Proceedings 2, no. 13 (November 13, 2018): 1022. http://dx.doi.org/10.3390/proceedings2131022.

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In the conventional culture systems in vitro, the challenging organoid approach have recently been overcome by the development of microfluidic Organ Chip models of human intestine. The potential future applications of Intestine-on-Chips in disease modelling, drug development and personalized medicine are leading research to identify and investigate limitations of modern chip-based systems and to focus the attention on the gut epithelium and its specific barrier function playing a significant role in many human disorders and diseases. In this paper, we propose and discuss the importance to implement a multi-parameter analysis on an engineered platform for developing an Epithelial Gut On Chip model.

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Cecen, Berivan, Christina Karavasili, Mubashir Nazir, Anant Bhusal, Elvan Dogan, Fatemeh Shahriyari, Sedef Tamburaci, Melda Buyukoz, Leyla Didem Kozaci, and Amir K. Miri. "Multi-Organs-on-Chips for Testing Small-Molecule Drugs: Challenges and Perspectives." Pharmaceutics 13, no. 10 (October 11, 2021): 1657. http://dx.doi.org/10.3390/pharmaceutics13101657.

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Organ-on-a-chip technology has been used in testing small-molecule drugs for screening potential therapeutics and regulatory protocols. The technology is expected to boost the development of novel therapies and accelerate the discovery of drug combinations in the coming years. This has led to the development of multi-organ-on-a-chip (MOC) for recapitulating various organs involved in the drug–body interactions. In this review, we discuss the current MOCs used in screening small-molecule drugs and then focus on the dynamic process of drug absorption, distribution, metabolism, and excretion. We also address appropriate materials used for MOCs at low cost and scale-up capacity suitable for high-performance analysis of drugs and commercial high-throughput screening platforms.

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Basak, Sayan. "Unlocking the future: converging multi-organ-on-a-chip on the current biomedical sciences." Emergent Materials 3, no. 5 (September 22, 2020): 693–709. http://dx.doi.org/10.1007/s42247-020-00124-y.

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Kim, Gyeong-Ji, Kwon-Jai Lee, Jeong-Woo Choi, and Jeung Hee An. "Drug Evaluation Based on a Multi-Channel Cell Chip with a Horizontal Co-Culture." International Journal of Molecular Sciences 22, no. 13 (June 29, 2021): 6997. http://dx.doi.org/10.3390/ijms22136997.

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We developed a multi-channel cell chip containing a three-dimensional (3D) scaffold for horizontal co-culture and drug toxicity screening in multi-organ culture (human glioblastoma, cervical cancer, normal liver cells, and normal lung cells). The polydimethylsiloxane (PDMS) multi-channel cell chip (PMCCC) was based on fused deposition modeling (FDM) technology. The architecture of the PMCCC was an open-type cell chip and did not require a pump or syringe. We investigated cell proliferation and cytotoxicity by conducting 3-(4,5-dimethylthiazol-2-yl)-2,5-dphenyltetrazolium bromide (MTT) and lactate dehydrogenase (LDH) assays and analysis of oleanolic acid (OA)-treated multi-channel cell chips. The results of the MTT and LDH assays showed that OA treatment in the multi-channel cell chip of four cell lines enhanced chemoresistance of cells compared with that in the 2D culture. Furthermore, we demonstrated the feasibility of the application of our multi-channel cell chip in various analysis methods through Annexin V-fluorescein isothiocyanate/propidium iodide staining, which is not used for conventional cell chips. Taken together, the results demonstrated that the PMCCC may be used as a new 3D platform because it enables simultaneous drug screening in multiple cells by single point injection and allows analysis of various biological processes.

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Palama, E., M. Aiello, and S. Scaglione. "200P A novel multi-organ on chip model for metastatic tumor biology understanding." Immuno-Oncology and Technology 20 (December 2023): 100676. http://dx.doi.org/10.1016/j.iotech.2023.100676.

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Bovard, David, Anita Iskandar, Karsta Luettich, Julia Hoeng, and Manuel C. Peitsch. "Organs-on-a-chip." Toxicology Research and Application 1 (January 1, 2017): 239784731772635. http://dx.doi.org/10.1177/2397847317726351.

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In the last few years, considerable attention has been given to in vitro models in an attempt to reduce the use of animals and to decrease the rate of preclinical failure associated with the development of new drugs. Simple two-dimensional cultures grown in a dish are now frequently replaced by organotypic cultures with three-dimensional (3-D) architecture, which enables interactions between cells, promoting their differentiation and increasing their in vivo likeness. Microengineering now enables the incorporation of small devices into 3-D culture models to reproduce the complex microenvironment of the modeled organ, often referred to as organs-on-a-chip (OoCs). This review describes various OoCs developed to mimic liver, brain, kidney, and lung tissues. Current challenges encountered in attempts to recreate the in vivo environment are described, as well as some examples of OoCs. Finally, attention is given to the ongoing evolution of OoCs with the aim of solving one of the major limitations in that they can only represent a single organ. Multi-organ-on-a-chip (MOC) systems mimic organ interactions observed in the human body and aim to provide the features of compound uptake, metabolism, and excretion, while simultaneously allowing for insights into biological effects. MOCs might therefore represent a new paradigm in drug development, providing a better understanding of dose responses and mechanisms of toxicity, enabling the detection of drug resistance and supporting the evaluation of pharmacokinetic–pharmacodynamics parameters.

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Dornhof, Johannes, Jochen Kieninger, Harshini Muralidharan, Jochen Maurer, Gerald A. Urban, and Andreas Weltin. "Microfluidic organ-on-chip system for multi-analyte monitoring of metabolites in 3D cell cultures." Lab on a Chip 22, no. 2 (2022): 225–39. http://dx.doi.org/10.1039/d1lc00689d.

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An organ-on-chip platform equipped with microsensors for long-term microfluidic cultivation and metabolic monitoring (O2, Glu, Lac) of 3D tumour organoid cultures grown from patient-derived single cancer stem cells.

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Fanizza, Francesca, Marzia Campanile, Gianluigi Forloni, Carmen Giordano, and Diego Albani. "Induced pluripotent stem cell-based organ-on-a-chip as personalized drug screening tools: A focus on neurodegenerative disorders." Journal of Tissue Engineering 13 (January 2022): 204173142210953. http://dx.doi.org/10.1177/20417314221095339.

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The Organ-on-a-Chip (OoC) technology shows great potential to revolutionize the drugs development pipeline by mimicking the physiological environment and functions of human organs. The translational value of OoC is further enhanced when combined with patient-specific induced pluripotent stem cells (iPSCs) to develop more realistic disease models, paving the way for the development of a new generation of patient-on-a-chip devices. iPSCs differentiation capacity leads to invaluable improvements in personalized medicine. Moreover, the connection of single-OoC into multi-OoC or body-on-a-chip allows to investigate drug pharmacodynamic and pharmacokinetics through the study of multi-organs cross-talks. The need of a breakthrough thanks to this technology is particularly relevant within the field of neurodegenerative diseases, where the number of patients is increasing and the successful rate in drug discovery is worryingly low. In this review we discuss current iPSC-based OoC as drug screening models and their implication in development of new therapies for neurodegenerative disorders.

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Soragni, Camilla, Gwenaëlle Rabussier, Leon J. de Windt, Sebastian J. Trietsch, Henriëtte L. Lanz, and Chee P. Ng. "High throughput assay to quantify oxidative stress in organ-on-a-chip placenta models in a multi-chip platform." Placenta 112 (September 2021): e26. http://dx.doi.org/10.1016/j.placenta.2021.07.087.

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Imparato, Giorgia, Francesco Urciuolo, and Paolo Antonio Netti. "Organ on Chip Technology to Model Cancer Growth and Metastasis." Bioengineering 9, no. 1 (January 11, 2022): 28. http://dx.doi.org/10.3390/bioengineering9010028.

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Organ on chip (OOC) has emerged as a major technological breakthrough and distinct model system revolutionizing biomedical research and drug discovery by recapitulating the crucial structural and functional complexity of human organs in vitro. OOC are rapidly emerging as powerful tools for oncology research. Indeed, Cancer on chip (COC) can ideally reproduce certain key aspects of the tumor microenvironment (TME), such as biochemical gradients and niche factors, dynamic cell–cell and cell–matrix interactions, and complex tissue structures composed of tumor and stromal cells. Here, we review the state of the art in COC models with a focus on the microphysiological systems that host multicellular 3D tissue engineering models and can help elucidate the complex biology of TME and cancer growth and progression. Finally, some examples of microengineered tumor models integrated with multi-organ microdevices to study disease progression in different tissues will be presented.

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Wang, Ying I., Carlota Oleaga, Christopher J. Long, Mandy B. Esch, Christopher W. McAleer, Paula G. Miller, James J. Hickman, and Michael L. Shuler. "Self-contained, low-cost Body-on-a-Chip systems for drug development." Experimental Biology and Medicine 242, no. 17 (February 17, 2017): 1701–13. http://dx.doi.org/10.1177/1535370217694101.

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Integrated multi-organ microphysiological systems are an evolving tool for preclinical evaluation of the potential toxicity and efficacy of drug candidates. Such systems, also known as Body-on-a-Chip devices, have a great potential to increase the successful conversion of drug candidates entering clinical trials into approved drugs. Systems, to be attractive for commercial adoption, need to be inexpensive, easy to operate, and give reproducible results. Further, the ability to measure functional responses, such as electrical activity, force generation, and barrier integrity of organ surrogates, enhances the ability to monitor response to drugs. The ability to operate a system for significant periods of time (up to 28 d) will provide potential to estimate chronic as well as acute responses of the human body. Here we review progress towards a self-contained low-cost microphysiological system with functional measurements of physiological responses. Impact statement Multi-organ microphysiological systems are promising devices to improve the drug development process. The development of a pumpless system represents the ability to build multi-organ systems that are of low cost, high reliability, and self-contained. These features, coupled with the ability to measure electrical and mechanical response in addition to chemical or metabolic changes, provides an attractive system for incorporation into the drug development process. This will be the most complete review of the pumpless platform with recirculation yet written.

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Zommiti, Mohamed, Nathalie Connil, Ali Tahrioui, Anne Groboillot, Corinne Barbey, Yoan Konto-Ghiorghi, Olivier Lesouhaitier, Sylvie Chevalier, and Marc G. J. Feuilloley. "Organs-on-Chips Platforms Are Everywhere: A Zoom on Biomedical Investigation." Bioengineering 9, no. 11 (November 3, 2022): 646. http://dx.doi.org/10.3390/bioengineering9110646.

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Over the decades, conventional in vitro culture systems and animal models have been used to study physiology, nutrient or drug metabolisms including mechanical and physiopathological aspects. However, there is an urgent need for Integrated Testing Strategies (ITS) and more sophisticated platforms and devices to approach the real complexity of human physiology and provide reliable extrapolations for clinical investigations and personalized medicine. Organ-on-a-chip (OOC), also known as a microphysiological system, is a state-of-the-art microfluidic cell culture technology that sums up cells or tissue-to-tissue interfaces, fluid flows, mechanical cues, and organ-level physiology, and it has been developed to fill the gap between in vitro experimental models and human pathophysiology. The wide range of OOC platforms involves the miniaturization of cell culture systems and enables a variety of novel experimental techniques. These range from modeling the independent effects of biophysical forces on cells to screening novel drugs in multi-organ microphysiological systems, all within microscale devices. As in living biosystems, the development of vascular structure is the salient feature common to almost all organ-on-a-chip platforms. Herein, we provide a snapshot of this fast-evolving sophisticated technology. We will review cutting-edge developments and advances in the OOC realm, discussing current applications in the biomedical field with a detailed description of how this technology has enabled the reconstruction of complex multi-scale and multifunctional matrices and platforms (at the cellular and tissular levels) leading to an acute understanding of the physiopathological features of human ailments and infections in vitro.

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Ribeiro, Mafalda, Pamela Ali, Benjamin Metcalfe, Despina Moschou, and Paulo R. F. Rocha. "Microfluidics Integration into Low-Noise Multi-Electrode Arrays." Micromachines 12, no. 6 (June 20, 2021): 727. http://dx.doi.org/10.3390/mi12060727.

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Organ-on-Chip technology is commonly used as a tool to replace animal testing in drug development. Cells or tissues are cultured on a microchip to replicate organ-level functions, where measurements of the electrical activity can be taken to understand how the cell populations react to different drugs. Microfluidic structures are integrated in these devices to replicate more closely an in vivo microenvironment. Research has provided proof of principle that more accurate replications of the microenvironment result in better micro-physiological behaviour, which in turn results in a higher predictive power. This work shows a transition from a no-flow (static) multi-electrode array (MEA) to a continuous-flow (dynamic) MEA, assuring a continuous and homogeneous transfer of an electrolyte solution across the measurement chamber. The process through which the microfluidic system was designed, simulated, and fabricated is described, and electrical characterisation of the whole structure under static solution and a continuous flow rate of 80 µL/min was performed. The latter reveals minimal background disturbance, with a background noise below 30 µVpp for all flow rates and areas. This microfluidic MEA, therefore, opens new avenues for more accurate and long-term recordings in Organ-on-Chip systems.

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Shinha, Kenta, Wataru Nihei, Tatsuto Ono, Ryota Nakazato, and Hiroshi Kimura. "A pharmacokinetic–pharmacodynamic model based on multi-organ-on-a-chip for drug–drug interaction studies." Biomicrofluidics 14, no. 4 (July 2020): 044108. http://dx.doi.org/10.1063/5.0011545.

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Yen, Daniel P., Yuta Ando, and Keyue Shen. "A cost-effective micromilling platform for rapid prototyping of microdevices." TECHNOLOGY 04, no. 04 (December 2016): 234–39. http://dx.doi.org/10.1142/s2339547816200041.

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Micromilling has great potential in producing microdevices for lab-on-a-chip and organ-on-a-chip applications, but has remained under-utilized due to the high machinery costs and limited accessibility. In this paper, we assessed the machining capabilities of a low-cost 3-D mill in polycarbonate material, which were showcased by the production of microfluidic devices. The study demonstrates that this particular mill is well suited for the fabrication of multi-scale microdevices with feature sizes from micrometers to centimeters.

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Cameron, Tiffany C., Avineet Randhawa, Samantha M. Grist, Tanya Bennet, Jessica Hua, Luis G. Alde, Tara M. Caffrey, Cheryl L. Wellington, and Karen C. Cheung. "PDMS Organ-On-Chip Design and Fabrication: Strategies for Improving Fluidic Integration and Chip Robustness of Rapidly Prototyped Microfluidic In Vitro Models." Micromachines 13, no. 10 (September 22, 2022): 1573. http://dx.doi.org/10.3390/mi13101573.

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The PDMS-based microfluidic organ-on-chip platform represents an exciting paradigm that has enjoyed a rapid rise in popularity and adoption. A particularly promising element of this platform is its amenability to rapid manufacturing strategies, which can enable quick adaptations through iterative prototyping. These strategies, however, come with challenges; fluid flow, for example, a core principle of organs-on-chip and the physiology they aim to model, necessitates robust, leak-free channels for potentially long (multi-week) culture durations. In this report, we describe microfluidic chip fabrication methods and strategies that are aimed at overcoming these difficulties; we employ a subset of these strategies to a blood–brain-barrier-on-chip, with others applied to a small-airway-on-chip. Design approaches are detailed with considerations presented for readers. Results pertaining to fabrication parameters we aimed to improve (e.g., the thickness uniformity of molded PDMS), as well as illustrative results pertaining to the establishment of cell cultures using these methods will also be presented.

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Shanti, Aya, Bisan Samara, Amal Abdullah, Nicholas Hallfors, Dino Accoto, Jiranuwat Sapudom, Aseel Alatoom, Jeremy Teo, Serena Danti, and Cesare Stefanini. "Multi-Compartment 3D-Cultured Organ-on-a-Chip: Towards a Biomimetic Lymph Node for Drug Development." Pharmaceutics 12, no. 5 (May 19, 2020): 464. http://dx.doi.org/10.3390/pharmaceutics12050464.

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The interaction of immune cells with drugs and/or with other cell types should be mechanistically investigated in order to reduce attrition of new drug development. However, they are currently only limited technologies that address this need. In our work, we developed initial but significant building blocks that enable such immune-drug studies. We developed a novel microfluidic platform replicating the Lymph Node (LN) microenvironment called LN-on-a-chip, starting from design all the way to microfabrication, characterization and validation in terms of architectural features, fluidics, cytocompatibility, and usability. To prove the biomimetics of this microenvironment, we inserted different immune cell types in a microfluidic device, which showed an in-vivo-like spatial distribution. We demonstrated that the developed LN-on-a-chip incorporates key features of the native human LN, namely, (i) similarity in extracellular matrix composition, morphology, porosity, stiffness, and permeability, (ii) compartmentalization of immune cells within distinct structural domains, (iii) replication of the lymphatic fluid flow pattern, (iv) viability of encapsulated cells in collagen over the typical timeframe of immunotoxicity experiments, and (v) interaction among different cell types across chamber boundaries. Further studies with this platform may assess the immune cell function as a step forward to disclose the effects of pharmaceutics to downstream immunology in more physiologically relevant microenvironments.

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Abu-Dawas, Sadeq, Hawra Alawami, Mohammed Zourob, and Qasem Ramadan. "Design and Fabrication of Low-Cost Microfluidic Chips and Microfluidic Routing System for Reconfigurable Multi-(Organ-on-a-Chip) Assembly." Micromachines 12, no. 12 (December 11, 2021): 1542. http://dx.doi.org/10.3390/mi12121542.

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A low-cost, versatile, and reconfigurable fluidic routing system and chip assembly have been fabricated and tested. The platform and its accessories were fabricated in-house without the need for costly and specialized equipment nor specific expertise. An agarose-based artificial membrane was integrated into the chips and employed to test the chip-to-chip communication in various configurations. Various chip assemblies were constructed and tested which demonstrate the versatile utility of the fluidic routing system that enables the custom design of the chip-to-chip communication and the possibility of fitting a variety of (organ-on-a-chip)-based biological models with multicell architectures. The reconfigurable chip assembly would enable selective linking/isolating the desired chip/compartment, hence allowing the study of the contribution of specific cell/tissue within the in vitro models.

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Lee, Hyuna, Dae Shik Kim, Sang Keun Ha, Inwook Choi, Jong Min Lee, and Jong Hwan Sung. "A pumpless multi-organ-on-a-chip (MOC) combined with a pharmacokinetic-pharmacodynamic (PK-PD) model." Biotechnology and Bioengineering 114, no. 2 (September 14, 2016): 432–43. http://dx.doi.org/10.1002/bit.26087.

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Grigorev, Georgii V., Alexander V. Lebedev, Xiaohao Wang, Xiang Qian, George V. Maksimov, and Liwei Lin. "Advances in Microfluidics for Single Red Blood Cell Analysis." Biosensors 13, no. 1 (January 9, 2023): 117. http://dx.doi.org/10.3390/bios13010117.

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The utilizations of microfluidic chips for single RBC (red blood cell) studies have attracted great interests in recent years to filter, trap, analyze, and release single erythrocytes for various applications. Researchers in this field have highlighted the vast potential in developing micro devices for industrial and academia usages, including lab-on-a-chip and organ-on-a-chip systems. This article critically reviews the current state-of-the-art and recent advances of microfluidics for single RBC analyses, including integrated sensors and microfluidic platforms for microscopic/tomographic/spectroscopic single RBC analyses, trapping arrays (including bifurcating channels), dielectrophoretic and agglutination/aggregation studies, as well as clinical implications covering cancer, sepsis, prenatal, and Sickle Cell diseases. Microfluidics based RBC microarrays, sorting/counting and trapping techniques (including acoustic, dielectrophoretic, hydrodynamic, magnetic, and optical techniques) are also reviewed. Lastly, organs on chips, multi-organ chips, and drug discovery involving single RBC are described. The limitations and drawbacks of each technology are addressed and future prospects are discussed.

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Safarzadeh, Melody, Lauren S. Richardson, Ananth Kumar Kammala, Angela Mosebarger, Mohamed Bettayeb, Sungjin Kim, Po Yi Lam, Enkhtuya Radnaa, Arum Han, and Ramkumar Menon. "A multi-organ, feto-maternal interface organ-on-chip, models pregnancy pathology and is a useful preclinical extracellular vesicle drug trial platform." Extracellular Vesicle 3 (June 2024): 100035. http://dx.doi.org/10.1016/j.vesic.2024.100035.

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Tunesi, Marta, Luca Izzo, Ilaria Raimondi, Diego Albani, and Carmen Giordano. "A miniaturized hydrogel-based in vitro model for dynamic culturing of human cells overexpressing beta-amyloid precursor protein." Journal of Tissue Engineering 11 (January 2020): 204173142094563. http://dx.doi.org/10.1177/2041731420945633.

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Recent findings have highlighted an interconnection between intestinal microbiota and the brain, referred to as microbiota–gut–brain axis, and suggested that alterations in microbiota composition might affect brain functioning, also in Alzheimer’s disease. To investigate microbiota–gut–brain axis biochemical pathways, in this work we developed an innovative device to be used as modular unit in an engineered multi-organ-on-a-chip platform recapitulating in vitro the main players of the microbiota–gut–brain axis, and an innovative three-dimensional model of brain cells based on collagen/hyaluronic acid or collagen/poly(ethylene glycol) semi-interpenetrating polymer networks and β-amyloid precursor protein-Swedish mutant-expressing H4 cells, to simulate the pathological scenario of Alzheimer’s disease. We set up the culturing conditions, assessed cell response, scaled down the three-dimensional models to be hosted in the organ-on-a-chip device, and cultured them both in static and in dynamic conditions. The results suggest that the device and three-dimensional models are exploitable for advanced engineered models representing brain features also in Alzheimer’s disease scenario.

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Sticker, Drago, Mario Rothbauer, Sarah Lechner, Marie-Therese Hehenberger, and Peter Ertl. "Multi-layered, membrane-integrated microfluidics based on replica molding of a thiol–ene epoxy thermoset for organ-on-a-chip applications." Lab on a Chip 15, no. 24 (2015): 4542–54. http://dx.doi.org/10.1039/c5lc01028d.

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Prete, Alessandro, Antonio Matrone, and Roberto Plebani. "State of the Art in 3D Culture Models Applied to Thyroid Cancer." Medicina 60, no. 4 (March 22, 2024): 520. http://dx.doi.org/10.3390/medicina60040520.

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Thyroid cancer (TC) is the prevalent endocrine tumor with a rising incidence, particularly in higher-income countries, leading to an increased interest in its management and treatment. While overall, survival rates for TC are usually favorable, advanced cases, especially with metastasis and specific histotypes, pose challenges with poorer outcomes, advocating the need of systemic treatments. Targeted therapies have shown efficacy in both preclinical models and clinical trials but face issues of resistance, since they usually induce partial and transient response. These resistance phenomena are currently only partially addressed by traditional preclinical models. This review explores the limitations of traditional preclinical models and emphasizes the potential of three-dimensional (3D) models, such as transwell assays, spheroids, organoids, and organ-on-chip technology in providing a more comprehensive understanding of TC pathogenesis and treatment responses. We reviewed their use in the TC field, highlighting how they can produce new interesting insights. Finally, the advent of organ-on-chip technology is currently revolutionizing preclinical research, offering dynamic, multi-cellular systems that replicate the complexity of human organs and cancer–host interactions.

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van Berlo, Damiën, Evita van de Steeg, Hossein Eslami Amirabadi, and Rosalinde Masereeuw. "The potential of multi-organ-on-chip models for assessment of drug disposition as alternative to animal testing." Current Opinion in Toxicology 27 (September 2021): 8–17. http://dx.doi.org/10.1016/j.cotox.2021.05.001.

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Rajan, Shiny Amala Priya, Julio Aleman, MeiMei Wan, Nima Pourhabibi Zarandi, Goodwell Nzou, Sean Murphy, Colin E. Bishop, et al. "Probing prodrug metabolism and reciprocal toxicity with an integrated and humanized multi-tissue organ-on-a-chip platform." Acta Biomaterialia 106 (April 2020): 124–35. http://dx.doi.org/10.1016/j.actbio.2020.02.015.

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Konopka, Joanna, Dominik Kołodziejek, Magdalena Flont, Agnieszka Żuchowska, Elżbieta Jastrzębska, and Zbigniew Brzózka. "Exploring Endothelial Expansion on a Chip." Sensors 22, no. 23 (December 2, 2022): 9414. http://dx.doi.org/10.3390/s22239414.

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Angiogenesis is the development of new blood vessels from the existing vasculature. Its malfunction leads to the development of cancers and cardiovascular diseases qualified by the WHO as a leading cause of death worldwide. A better understanding of mechanisms regulating physiological and pathological angiogenesis will potentially contribute to developing more effective treatments for those urgent issues. Therefore, the main goal of the following study was to design and manufacture an angiogenesis-on-a-chip microplatform, including cylindrical microvessels created by Viscous Finger Patterning (VFP) technique and seeded with HUVECs. While optimizing the VFP procedure, we have observed that lumen’s diameter decreases with a diminution of the droplet’s volume. The influence of Vascular Endothelial Growth Factor (VEGF) with a concentration of 5, 25, 50, and 100 ng/mL on the migration of HUVECs was assessed. VEGF’s solution with concentrations varying from 5 to 50 ng/mL reveals high angiogenic potential. The spatial arrangement of cells and their morphology were visualized by fluorescence and confocal microscopy. Migration of HUVECs toward loaded angiogenic stimuli has been initiated after overnight incubation. This research is the basis for developing more complex vascularized multi-organ-on-a-chip microsystems that could potentially be used for drug screening.

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Oleaga, Carlota, Anne Riu, Sandra Rothemund, Andrea Lavado, Christopher W. McAleer, Christopher J. Long, Keisha Persaud, et al. "Investigation of the effect of hepatic metabolism on off-target cardiotoxicity in a multi-organ human-on-a-chip system." Biomaterials 182 (November 2018): 176–90. http://dx.doi.org/10.1016/j.biomaterials.2018.07.062.

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Poloznikov, A. A. "MicroRNA Pattern of Culture Medium as a Substrate for the Analysis of Lysis of Cell Subpopulations in Multiorgan Cell Models." Biotekhnologiya 37, no. 2 (2021): 76–80. http://dx.doi.org/10.21519/0234-2758-2021-37-2-76-80.

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A method has been developed for assessing the proportion of lysed MDA-MB-231 cells cultured in the multi-organ human-on-a-chip model based on the determination of the hsa-miR-222-3p and hsa-miR-99b-5p microRNA levels in the culture medium. The threshold levels of microRNA expression were calculated, which made it possible to estimate the proportion of lysed cells with an accuracy of 25%. microRNA, breast cancer, cell model This work was supported by the Ministry of Education and Science of the Russian Federation (grant RFMEFI61618X0092).

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Fedi, Arianna, Chiara Vitale, Marco Fato, and Silvia Scaglione. "A Human Ovarian Tumor & Liver Organ-on-Chip for Simultaneous and More Predictive Toxo-Efficacy Assays." Bioengineering 10, no. 2 (February 18, 2023): 270. http://dx.doi.org/10.3390/bioengineering10020270.

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In oncology, the poor success rate of clinical trials is becoming increasingly evident due to the weak predictability of preclinical assays, which either do not recapitulate the complexity of human tissues (i.e., in vitro tests) or reveal species-specific outcomes (i.e., animal testing). Therefore, the development of novel approaches is fundamental for better evaluating novel anti-cancer treatments. Here, a multicompartmental organ-on-chip (OOC) platform was adopted to fluidically connect 3D ovarian cancer tissues to hepatic cellular models and resemble the systemic cisplatin administration for contemporarily investigating drug efficacy and hepatotoxic effects in a physiological context. Computational fluid dynamics was performed to impose capillary-like blood flows and predict cisplatin diffusion. After a cisplatin concentration screening using 2D/3D tissue models, cytotoxicity assays were conducted in the multicompartmental OOC and compared with static co-cultures and dynamic single-organ models. A linear decay of SKOV-3 ovarian cancer and HepG2 liver cell viability was observed with increasing cisplatin concentration. Furthermore, 3D ovarian cancer models showed higher drug resistance than the 2D model in static conditions. Most importantly, when compared to clinical therapy, the experimental approach combining 3D culture, fluid-dynamic conditions, and multi-organ connection displayed the most predictive toxicity and efficacy results, demonstrating that OOC-based approaches are reliable 3Rs alternatives in preclinic.

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Safarzadeh, Melody, Lauren Richardson, Ananth Kumar Kammala, Angela Mosebarger, Mohamed Bettayeb, Enkhtuya Radnaa, Sungjin Kim, Po Yi Lam, Arum Han, and RamKumar Menon. "306 A multi-organ-on-chip model to study the efficacy of exosomal therapeutics in treating inflammation-associated adverse pregnancies." American Journal of Obstetrics and Gynecology 230, no. 1 (January 2024): S175. http://dx.doi.org/10.1016/j.ajog.2023.11.328.

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Safarzadeh, Melody, Lauren Richardson, Ananth Kumar Kammala, Enkhtuya Radnaa, Sungjin Kim, Po Yi Lam, Arum Han, and RamKumar Menon. "305 A multi-organ fetal membrane-placenta-on-chip platform to study the transmission of infection and inflammation during pregnancy." American Journal of Obstetrics and Gynecology 230, no. 1 (January 2024): S174—S175. http://dx.doi.org/10.1016/j.ajog.2023.11.327.

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Díaz Lantada, Andrés, Wilhelm Pfleging, Heino Besser, Markus Guttmann, Markus Wissmann, Klaus Plewa, Peter Smyrek, Volker Piotter, and Josefa García-Ruíz. "Research on the Methods for the Mass Production of Multi-Scale Organs-On-Chips." Polymers 10, no. 11 (November 7, 2018): 1238. http://dx.doi.org/10.3390/polym10111238.

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The success of labs- and organs-on-chips as transformative technologies in the biomedical arena relies on our capacity of solving some current challenges related to their design, modeling, manufacturability, and usability. Among present needs for the industrial scalability and impact promotion of these bio-devices, their sustainable mass production constitutes a breakthrough for reaching the desired level of repeatability in systematic testing procedures based on labs- and organs-on-chips. The use of adequate biomaterials for cell-culture processes and the achievement of the multi-scale features required, for in vitro modeling the physiological interactions among cells, tissues, and organoids, which prove to be demanding requirements in terms of production. This study presents an innovative synergistic combination of technologies, including: laser stereolithography, laser material processing on micro-scale, electroforming, and micro-injection molding, which enables the rapid creation of multi-scale mold cavities for the industrial production of labs- and organs-on-chips using thermoplastics apt for in vitro testing. The procedure is validated by the design, rapid prototyping, mass production, and preliminary testing with human mesenchymal stem cells of a conceptual multi-organ-on-chip platform, which is conceived for future studies linked to modeling cell-to-cell communication, understanding cell-material interactions, and studying metastatic processes.

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Journal articles on the topic 'Multi-organ-on-chip'

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