Journal articles: 'Tissue-on-chip'

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Narciso, Cody, Kyle R. Cowdrick, Victoria Zellmer, Teresa Brito-Robinson, Pavel Brodskiy, David J. Hoelzle, Siyuan Zhang, and Jeremiah J. Zartman. "On-chip three-dimensional tissue histology for microbiopsies." Biomicrofluidics 10, no. 2 (March 2016): 021101. http://dx.doi.org/10.1063/1.4941708.

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Dorrigiv, Dina, Kayla Simeone, Laudine Communal, Jennifer Kendall-Dupont, Amélie St-Georges-Robillard, Benjamin Péant, Euridice Carmona, Anne-Marie Mes-Masson, and Thomas Gervais. "Microdissected Tissue vs Tissue Slices—A Comparative Study of Tumor Explant Models Cultured On-Chip and Off-Chip." Cancers 13, no. 16 (August 21, 2021): 4208. http://dx.doi.org/10.3390/cancers13164208.

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Predicting patient responses to anticancer drugs is a major challenge both at the drug development stage and during cancer treatment. Tumor explant culture platforms (TECPs) preserve the native tissue architecture and are well-suited for drug response assays. However, tissue longevity in these models is relatively low. Several methodologies have been developed to address this issue, although no study has compared their efficacy in a controlled fashion. We investigated the effect of two variables in TECPs, specifically, the tissue size and culture vessel on tissue survival using micro-dissected tumor tissue (MDT) and tissue slices which were cultured in microfluidic chips and plastic well plates. Tumor models were produced from ovarian and prostate cancer cell line xenografts and were matched in terms of the specimen, total volume of tissue, and respective volume of medium in each culture system. We examined morphology, viability, and hypoxia in the various tumor models. Our observations suggest that the viability and proliferative capacity of MDTs were not affected during the time course of the experiments. In contrast, tissue slices had reduced proliferation and showed increased cell death and hypoxia under both culture conditions. Tissue slices cultured in microfluidic devices had a lower degree of hypoxia compared to those in 96-well plates. Globally, our results show that tissue slices have lower survival rates compared to MDTs due to inherent diffusion limitations, and that microfluidic devices may decrease hypoxia in tumor models.

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Tavakol, Daniel Naveed, Sharon Fleischer, and Gordana Vunjak-Novakovic. "Harnessing organs-on-a-chip to model tissue regeneration." Cell Stem Cell 28, no. 6 (June 2021): 993–1015. http://dx.doi.org/10.1016/j.stem.2021.05.008.

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Authasing, S., S. Chantanetra, S.Mitatha, and P. P. Yupapin. "Tissue Culture On-chip Design using Multivariable Molecular Network." Procedia Engineering 32 (2012): 286–90. http://dx.doi.org/10.1016/j.proeng.2012.01.1269.

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WANG, Wei-Xin, Wei-Ping LIU, Bin WU, Guang-Tie LIANG, and Da-Yu LIU. "Construction of Tumor Tissue Microarray on a Microfluidic Chip." Chinese Journal of Analytical Chemistry 43, no. 5 (May 2015): 637–42. http://dx.doi.org/10.1016/s1872-2040(15)60823-4.

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Haim, Yulia, Tanya Tarnovscki, Dana Bashari, and Assaf Rudich. "A chromatin immunoprecipitation (ChIP) protocol for use in whole human adipose tissue." American Journal of Physiology-Endocrinology and Metabolism 305, no. 9 (November 1, 2013): E1172—E1177. http://dx.doi.org/10.1152/ajpendo.00598.2012.

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Chromatin immunoprecipitation (ChIP) has become a central method when studying in vivo protein-DNA interactions, with the major challenge being the hope to capture “authentic” interactions. While ChIP protocols have been optimized for use with specific cell types and tissues including adipose tissue-derived cells, a working ChIP protocol addressing the challenges imposed by fresh whole human adipose tissue has not been described. Utilizing human paired omental and subcutaneous adipose tissue obtained during elective abdominal surgeries, we have carefully identified and optimized individual steps in the ChIP protocol employed directly on fresh tissue fragments. We describe a complete working protocol for using ChIP on whole adipose tissue fragments. Specific steps required adaptation of the ChIP protocol to human whole adipose tissue. In particular, a cross-linking step was performed directly on fresh small tissue fragments. Nuclei were isolated before releasing chromatin, allowing better management of fat content; a sonication protocol to obtain fragmented chromatin was optimized. We also demonstrate the high sensitivity of immunoprecipitated chromatin from adipose tissue to freezing. In conclusion, we describe the development of a ChIP protocol optimized for use in studying whole human adipose tissue, providing solutions for the unique challenges imposed by this tissue. Unraveling protein-DNA interaction in whole human adipose tissue will likely contribute to elucidating molecular pathways contributing to common human diseases such as obesity and type 2 diabetes.

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Nitsche, Katharina S., Iris Müller, Sophie Malcomber, Paul L. Carmichael, and Hans Bouwmeester. "Implementing organ-on-chip in a next-generation risk assessment of chemicals: a review." Archives of Toxicology 96, no. 3 (February 1, 2022): 711–41. http://dx.doi.org/10.1007/s00204-022-03234-0.

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AbstractOrgan-on-chip (OoC) technology is full of engineering and biological challenges, but it has the potential to revolutionize the Next-Generation Risk Assessment of novel ingredients for consumer products and chemicals. A successful incorporation of OoC technology into the Next-Generation Risk Assessment toolbox depends on the robustness of the microfluidic devices and the organ tissue models used. Recent advances in standardized device manufacturing, organ tissue cultivation and growth protocols offer the ability to bridge the gaps towards the implementation of organ-on-chip technology. Next-Generation Risk Assessment is an exposure-led and hypothesis-driven tiered approach to risk assessment using detailed human exposure information and the application of appropriate new (non-animal) toxicological testing approaches. Organ-on-chip presents a promising in vitro approach by combining human cell culturing with dynamic microfluidics to improve physiological emulation. Here, we critically review commercial organ-on-chip devices, as well as recent tissue culture model studies of the skin, intestinal barrier and liver as the main metabolic organ to be used on-chip for Next-Generation Risk Assessment. Finally, microfluidically linked tissue combinations such as skin–liver and intestine–liver in organ-on-chip devices are reviewed as they form a relevant aspect for advancing toxicokinetic and toxicodynamic studies. We point to recent achievements and challenges to overcome, to advance non-animal, human-relevant safety studies.

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Moradi, Ehsanollah, Sasan Jalili-Firoozinezhad, and Mehran Solati-Hashjin. "Microfluidic organ-on-a-chip models of human liver tissue." Acta Biomaterialia 116 (October 2020): 67–83. http://dx.doi.org/10.1016/j.actbio.2020.08.041.

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Zoio, Patrícia, Sara Lopes-Ventura, and Abel Oliva. "Barrier-on-a-Chip with a Modular Architecture and Integrated Sensors for Real-Time Measurement of Biological Barrier Function." Micromachines 12, no. 7 (July 12, 2021): 816. http://dx.doi.org/10.3390/mi12070816.

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Biological barriers are essential for the maintenance of organ homeostasis and their dysfunction is responsible for many prevalent diseases. Advanced in vitro models of biological barriers have been developed through the combination of 3D cell culture techniques and organ-on-chip (OoC) technology. However, real-time monitoring of tissue function inside the OoC devices has been challenging, with most approaches relying on off-chip analysis and imaging techniques. In this study, we designed and fabricated a low-cost barrier-on-chip (BoC) device with integrated electrodes for the development and real-time monitoring of biological barriers. The integrated electrodes were used to measure transepithelial electrical resistance (TEER) during tissue culture, thereby quantitatively evaluating tissue barrier function. A finite element analysis was performed to study the sensitivity of the integrated electrodes and to compare them with conventional systems. As proof-of-concept, a full-thickness human skin model (FTSm) was grown on the developed BoC, and TEER was measured on-chip during the culture. After 14 days of culture, the barrier tissue was challenged with a benchmark irritant and its impact was evaluated on-chip through TEER measurements. The developed BoC with an integrated sensing capability represents a promising tool for real-time assessment of barrier function in the context of drug testing and disease modelling.

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Sateesh, Jasti, Koushik Guha, Arindam Dutta, Pratim Sengupta, Dhanya Yalamanchili, Nanda Sai Donepudi, M. Surya Manoj, and Sk Shahrukh Sohail. "A comprehensive review on advancements in tissue engineering and microfluidics toward kidney-on-chip." Biomicrofluidics 16, no. 4 (July 2022): 041501. http://dx.doi.org/10.1063/5.0087852.

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This review provides a detailed literature survey on microfluidics and its road map toward kidney-on-chip technology. The whole review has been tailored with a clear description of crucial milestones in regenerative medicine, such as bioengineering, tissue engineering, microfluidics, microfluidic applications in biomedical engineering, capabilities of microfluidics in biomimetics, organ-on-chip, kidney-on-chip for disease modeling, drug toxicity, and implantable devices. This paper also presents future scope for research in the bio-microfluidics domain and biomimetics domain.

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Ferrari, Erika, Cecilia Palma, Simone Vesentini, Paola Occhetta, and Marco Rasponi. "Integrating Biosensors in Organs-on-Chip Devices: A Perspective on Current Strategies to Monitor Microphysiological Systems." Biosensors 10, no. 9 (August 28, 2020): 110. http://dx.doi.org/10.3390/bios10090110.

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Organs-on-chip (OoC), often referred to as microphysiological systems (MPS), are advanced in vitro tools able to replicate essential functions of human organs. Owing to their unprecedented ability to recapitulate key features of the native cellular environments, they represent promising tools for tissue engineering and drug screening applications. The achievement of proper functionalities within OoC is crucial; to this purpose, several parameters (e.g., chemical, physical) need to be assessed. Currently, most approaches rely on off-chip analysis and imaging techniques. However, the urgent demand for continuous, noninvasive, and real-time monitoring of tissue constructs requires the direct integration of biosensors. In this review, we focus on recent strategies to miniaturize and embed biosensing systems into organs-on-chip platforms. Biosensors for monitoring biological models with metabolic activities, models with tissue barrier functions, as well as models with electromechanical properties will be described and critically evaluated. In addition, multisensor integration within multiorgan platforms will be further reviewed and discussed.

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Benam, Kambez Hajipouran. "Organ-on-Chip Meets Immunology: Let’s Start with the Lungs." Journal of Immunology 204, no. 1_Supplement (May 1, 2020): 159.14. http://dx.doi.org/10.4049/jimmunol.204.supp.159.14.

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Abstract Organs-on-chips are biomimetic, microfluidic, cell culture devices created with microchip manufacturing methods that contain continuously perfused hollow microchannels inhabited by living tissue cells arranged to simulate organ-level physiology. By recapitulating the multicellular architectures, tissue-tissue interfaces, chemical gradients, mechanical cues, and vascular perfusion of the body, these devices produce levels of tissue and organ functionality not possible with conventional 2D or 3D culture systems. They also enable high-resolution, real-time imaging and in vitro analysis of biochemical, genetic and metabolic activities of living human cells in a functional human tissue and organ context. Here, we discuss development of ‘Human Lung Small Airway-on-a-Chip’ – an engineered cell-by-cell reconstituted microfluidic device with living human tissues to model airway inflammation in the context of debilitating lung diseases, including asthma and chronic obstructive pulmonary disease (COPD). In addition, we will present our preliminary data on recreating a hematopoietically active bone marrow niche in vitro (‘BM-on-a-Chip’) for microphysiological integration with the Small Airway-on-a-Chip to emulate innate immune cell egress into circulation (from the BM) and their recruitment to the lung airway.

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Ko, Jihoon, Dohyun Park, Somin Lee, Burcu Gumuscu, and Noo Li Jeon. "Engineering Organ-on-a-Chip to Accelerate Translational Research." Micromachines 13, no. 8 (July 28, 2022): 1200. http://dx.doi.org/10.3390/mi13081200.

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We guide the use of organ-on-chip technology in tissue engineering applications. Organ-on-chip technology is a form of microengineered cell culture platform that elaborates the in-vivo like organ or tissue microenvironments. The organ-on-chip platform consists of microfluidic channels, cell culture chambers, and stimulus sources that emulate the in-vivo microenvironment. These platforms are typically engraved into an oxygen-permeable transparent material. Fabrication of these materials requires the use of microfabrication strategies, including soft lithography, 3D printing, and injection molding. Here we provide an overview of what is an organ-on-chip platform, where it can be used, what it is composed of, how it can be fabricated, and how it can be operated. In connection with this topic, we also introduce an overview of the recent applications, where different organs are modeled on the microscale using this technology.

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Zhu, Jingyi, Jiacheng He, Michael Verano, Ayoola T. Brimmo, Ayoub Glia, Mohammad A. Qasaimeh, Pengyu Chen, Jose O. Aleman, and Weiqiang Chen. "An integrated adipose-tissue-on-chip nanoplasmonic biosensing platform for investigating obesity-associated inflammation." Lab on a Chip 18, no. 23 (2018): 3550–60. http://dx.doi.org/10.1039/c8lc00605a.

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Kratz, Sebastian, Gregor Höll, Patrick Schuller, Peter Ertl, and Mario Rothbauer. "Latest Trends in Biosensing for Microphysiological Organs-on-a-Chip and Body-on-a-Chip Systems." Biosensors 9, no. 3 (September 19, 2019): 110. http://dx.doi.org/10.3390/bios9030110.

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Organs-on-chips are considered next generation in vitro tools capable of recreating in vivo like, physiological-relevant microenvironments needed to cultivate 3D tissue-engineered constructs (e.g., hydrogel-based organoids and spheroids) as well as tissue barriers. These microphysiological systems are ideally suited to (a) reduce animal testing by generating human organ models, (b) facilitate drug development and (c) perform personalized medicine by integrating patient-derived cells and patient-derived induced pluripotent stem cells (iPSCs) into microfluidic devices. An important aspect of any diagnostic device and cell analysis platform, however, is the integration and application of a variety of sensing strategies to provide reliable, high-content information on the health status of the in vitro model of choice. To overcome the analytical limitations of organs-on-a-chip systems a variety of biosensors have been integrated to provide continuous data on organ-specific reactions and dynamic tissue responses. Here, we review the latest trends in biosensors fit for monitoring human physiology in organs-on-a-chip systems including optical and electrochemical biosensors.

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Gjorevski, Nikolce, Blandine Avignon, Régine Gérard, Lauriane Cabon, Adrian B. Roth, Michael Bscheider, and Annie Moisan. "Neutrophilic infiltration in organ-on-a-chip model of tissue inflammation." Lab on a Chip 20, no. 18 (2020): 3365–74. http://dx.doi.org/10.1039/d0lc00417k.

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We describe a microphysiological model of intestinal inflammation, which incorporates and captures the functional interactions between an epithelial barrier, resident macrophages, infiltrating neutrophils, and extrcellular matrix degradation products.

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Macdonald, N. P., A. Menachery, J. Reboud, and J. M. Cooper. "Creating tissue on chip constructs in microtitre plates for drug discovery." RSC Advances 8, no. 18 (2018): 9603–10. http://dx.doi.org/10.1039/c8ra00849c.

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LIN, Dong-Guo, Jin-Qiong LIN, Pei-Wen LI, Na YANG, Bang-Lao XU, and Da-Yu LIU. "Construction of Tumor Tissue Array on An Open-Access Microfluidic Chip." Chinese Journal of Analytical Chemistry 46, no. 1 (January 2018): 113–20. http://dx.doi.org/10.1016/s1872-2040(17)61064-8.

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Nieskens, Tom T. G., and Martijn J. Wilmer. "Kidney-on-a-chip technology for renal proximal tubule tissue reconstruction." European Journal of Pharmacology 790 (November 2016): 46–56. http://dx.doi.org/10.1016/j.ejphar.2016.07.018.

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Zhang, Yu Shrike, Julio Aleman, Andrea Arneri, Simone Bersini, Francesco Piraino, Su Ryon Shin, Mehmet Remzi Dokmeci, and Ali Khademhosseini. "From cardiac tissue engineering to heart-on-a-chip: beating challenges." Biomedical Materials 10, no. 3 (June 11, 2015): 034006. http://dx.doi.org/10.1088/1748-6041/10/3/034006.

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Tsai, Hsieh-Fu, Alen Trubelja, Amy Q. Shen, and Gang Bao. "Tumour-on-a-chip: microfluidic models of tumour morphology, growth and microenvironment." Journal of The Royal Society Interface 14, no. 131 (June 2017): 20170137. http://dx.doi.org/10.1098/rsif.2017.0137.

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Cancer remains one of the leading causes of death, albeit enormous efforts to cure the disease. To overcome the major challenges in cancer therapy, we need to have a better understanding of the tumour microenvironment (TME), as well as a more effective means to screen anti-cancer drug leads; both can be achieved using advanced technologies, including the emerging tumour-on-a-chip technology. Here, we review the recent development of the tumour-on-a-chip technology, which integrates microfluidics, microfabrication, tissue engineering and biomaterials research, and offers new opportunities for building and applying functional three-dimensional in vitro human tumour models for oncology research, immunotherapy studies and drug screening. In particular, tumour-on-a-chip microdevices allow well-controlled microscopic studies of the interaction among tumour cells, immune cells and cells in the TME, of which simple tissue cultures and animal models are not amenable to do. The challenges in developing the next-generation tumour-on-a-chip technology are also discussed.

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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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Santoso, Jeffrey W., and Megan L. McCain. "Neuromuscular disease modeling on a chip." Disease Models & Mechanisms 13, no. 7 (July 1, 2020): dmm044867. http://dx.doi.org/10.1242/dmm.044867.

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ABSTRACTOrgans-on-chips are broadly defined as microfabricated surfaces or devices designed to engineer cells into microscale tissues with native-like features and then extract physiologically relevant readouts at scale. Because they are generally compatible with patient-derived cells, these technologies can address many of the human relevance limitations of animal models. As a result, organs-on-chips have emerged as a promising new paradigm for patient-specific disease modeling and drug development. Because neuromuscular diseases span a broad range of rare conditions with diverse etiology and complex pathophysiology, they have been especially challenging to model in animals and thus are well suited for organ-on-chip approaches. In this Review, we first briefly summarize the challenges in neuromuscular disease modeling with animal models. Next, we describe a variety of existing organ-on-chip approaches for neuromuscular tissues, including a survey of cell sources for both muscle and nerve, and two- and three-dimensional neuromuscular tissue-engineering techniques. Although researchers have made tremendous advances in modeling neuromuscular diseases on a chip, the remaining challenges in cell sourcing, cell maturity, tissue assembly and readout capabilities limit their integration into the drug development pipeline today. However, as the field advances, models of healthy and diseased neuromuscular tissues on a chip, coupled with animal models, have vast potential as complementary tools for modeling multiple aspects of neuromuscular diseases and identifying new therapeutic strategies.

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Haddadin, Zaid, Trinity Pike, Jebin J. Moses, and Lisa V. Poulikakos. "Colorimetric metasurfaces shed light on fibrous biological tissue." Journal of Materials Chemistry C 9, no. 35 (2021): 11619–39. http://dx.doi.org/10.1039/d1tc02030g.

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Fibrotic diseases affect all human organs (left), yet the selective visualization of tissue microstructure remains challenging in clinical and industrial settings. Colorimetric metasurfaces (right) address this challenge with an on-chip platform.

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Koch, Eugen V., Verena Ledwig, Sebastian Bendas, Stephan Reichl, and Andreas Dietzel. "Tissue Barrier-on-Chip: A Technology for Reproducible Practice in Drug Testing." Pharmaceutics 14, no. 7 (July 12, 2022): 1451. http://dx.doi.org/10.3390/pharmaceutics14071451.

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One key application of organ-on-chip systems is the examination of drug transport and absorption through native cell barriers such the blood–brain barrier. To overcome previous hurdles related to the transferability of existing static cell cultivation protocols and polydimethylsiloxane (PDMS) as the construction material, a chip platform with key innovations for practical use in drug-permeation testing is presented. First, the design allows for the transfer of barrier-forming tissue into the microfluidic system after cells have been seeded on porous polymer or Si3N4 membranes. From this, we can follow highly reproducible models and cultivation protocols established for static drug testing, from coating the membrane to seeding the cells and cell analysis. Second, the perfusion system is a microscopable glass chip with two fluid compartments with transparent embedded electrodes separated by the membrane. The reversible closure in a clamping adapter requires only a very thin PDMS sealing with negligible liquid contact, thereby eliminating well-known disadvantages of PDMS, such as its limited usability in the quantitative measurements of hydrophobic drug molecule concentrations. Equipped with tissue transfer capabilities, perfusion chamber inertness and air bubble trapping, and supplemented with automated fluid control, the presented system is a promising platform for studying established in vitro models of tissue barriers under reproducible microfluidic perfusion conditions.

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Olubajo, Farouk, Shailendra Achawal, Chittoor Rajaraman, Gerry O’Reilly, and John Greenman. "INNV-03. A MICROFLUIDIC CULTURE PARADIGM FOR THE EX VIVO MAINTENANCE OF HUMAN GLIOBLASTOMA TISSUE - A NEW GBM MODEL?" Neuro-Oncology 21, Supplement_6 (November 2019): vi130—vi131. http://dx.doi.org/10.1093/neuonc/noz175.546.

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Abstract The genetic and molecular variations that exist within Glioblastoma (GBM) determine treatment responses. One way to improve patient outcomes is to optimise treatment(s) pre-clinically by studying each tumour on an individual basis. Presented here are the results of a pilot study on the maintenance of human GBM tissue on a microfluidic platform. The device, fabricated using a photolithographic process, was composed of two layers of glass bonded together to contain a tissue chamber and a network of microchannels. A thin mesh layer was inserted to separate the tissue chamber from the microchannels and prevented blockage of the chip. Over an 18-month period, 33 patients were recruited, and 128 tissue sections were maintained in microfluidic devices for an average of 72 hours (h). Tissue viability as measured by Annexin V and Propidium Iodide staining showed that viability was 61.1 % in tissue maintained on chip after 72 h, compared with 68.9 % for fresh tissue analysed at the commencement of the experiment (P < 0.05). Other biomarkers, including Lactate Dehydrogenase (LDH) release and Trypan Blue assay, supported the viability of the tissue maintained on chip. Histological appearances of the tissue remained unchanged during the maintenance period and immunohistochemical analysis of Ki67 and Caspase 3 also showed no statistically significant differences. Analysis has shown a trend with tumours associated with poorer prognoses (e.g. recurrent tumours and IDH wildtype) displaying higher viability on chip compared to tumours linked with better outcomes (Grade 1–3 gliomas, IDH mutants and primary tumours). This work has demonstrated for the first time that human GBM tissue can be maintained ex vivo within a microfluidic device with viability comparable to fresh tissue samples. The model has the potential to be developed as a new platform for studying the biology of brain tumours, with the aim of facilitating personalised treatments.

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Singh, Abhishek A., Karianne Schuurman, Ekaterina Nevedomskaya, Suzan Stelloo, Simon Linder, Marjolein Droog, Yongsoo Kim, et al. "Optimized ChIP-seq method facilitates transcription factor profiling in human tumors." Life Science Alliance 2, no. 1 (December 28, 2018): e201800115. http://dx.doi.org/10.26508/lsa.201800115.

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Chromatin immunoprecipitation (ChIP)-seq analyses of transcription factors in clinical specimens are challenging due to the technical limitations and low quantities of starting material, often resulting in low enrichments and poor signal-to-noise ratio. Here, we present an optimized protocol for transcription factor ChIP-seq analyses in human tissue, yielding an ∼100% success rate for all transcription factors analyzed. As proof of concept and to illustrate general applicability of the approach, human tissue from the breast, prostate, and endometrial cancers were analyzed. In addition to standard formaldehyde fixation, disuccinimidyl glutarate was included in the procedure, greatly increasing data quality. To illustrate the sensitivity of the optimized protocol, we provide high-quality ChIP-seq data for three independent factors (AR, FOXA1, and H3K27ac) from a single core needle prostate cancer biopsy specimen. In summary, double-cross-linking strongly improved transcription factor ChIP-seq quality on human tumor samples, further facilitating and enhancing translational research on limited amounts of tissue.

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Firatligil‐Yildirir, Burcu, Gizem Bati‐Ayaz, Ismail Tahmaz, Muge Bilgen, Devrim Pesen‐Okvur, and Ozden Yalcin‐Ozuysal. "On‐chip determination of tissue‐specific metastatic potential of breast cancer cells." Biotechnology and Bioengineering 118, no. 10 (June 21, 2021): 3799–810. http://dx.doi.org/10.1002/bit.27855.

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Cecen, Berivan, Ayca Bal‐Ozturk, Gokcen Yasayan, Emine Alarcin, Polen Kocak, Rumeysa Tutar, Leyla Didem Kozaci, Su Ryon Shin, and Amir K. Miri. "Selection of natural biomaterials for micro‐tissue and organ‐on‐chip models." Journal of Biomedical Materials Research Part A 110, no. 5 (January 31, 2022): 1147–65. http://dx.doi.org/10.1002/jbm.a.37353.

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Ross, Ashley E., and Rebecca R. Pompano. "Diffusional analysis of cytokines in lymph node tissue on a microfluidic chip." Journal of Immunology 198, no. 1_Supplement (May 1, 2017): 63.2. http://dx.doi.org/10.4049/jimmunol.198.supp.63.2.

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Abstract Cytokines must diffuse between immune synapses, to neighboring cells, and across the lymph node in order to propagate specific immune responses. However, cytokine diffusion in the tissue environment has never been measured, making it difficult to model cell-cell signaling or the localization of cytokine therapeutics. Here, we analyzed the diffusion of TNF-α, IFN-γ, and IL-2, selected because they have central roles in immunity, they represent two different structural classes, and they vary in molecular weight and multimerization. We utilized a microfluidic platform to deliver picogram quantities of fluorescently labelled cytokines to specific regions of 300-μm thick slices of live murine lymph node tissue ex vivo and analyzed spread by fluorescent microscopy. The analysis method was compared to FRAP and microinjection techniques by analyzing diffusion of 10 kDa and 40 kDa Dextrans in both agarose and tissue slices. With the device, we were able to analyze diffusion of cytokines within the B-cell and T-cell zones of the tissue separately. On average, both TNF-α and IFN-γ diffused at the same rate in both the T-cell and B-cell zone (TNF-α: 2.5 ± 0.8 and 2.5 ± 1.6 × 10−7 cm2/s and IFN-γ: 6.0 ± 1.8 and 4.9 ± 1.5 × 10−7 cm2/s respectively, n = 7–9, p > 0.05); however, IL-2 diffused more rapidly in the T-cell zone (8.1 ±1.1 × 10−7 cm2/s, n = 7–8) than in the B-cell zone (4.5 ± 0.3 × 10−7 cm2/s, n = 7–8) yet the difference was not significant (p>0.05). Variation in diffusion between different zones suggests that cytokines interact differently within specific environments. This data provides the first diffusional analysis of cytokines in intact lymph node tissue and validates a new method to enhance the understanding of cell signaling kinetics.

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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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Kameda, Yoshikazu, Surachada Chuaychob, Miwa Tanaka, Yang Liu, Ryu Okada, Kazuya Fujimoto, Takuro Nakamura, and Ryuji Yokokawa. "Three-dimensional tissue model in direct contact with an on-chip vascular bed enabled by removable membranes." Lab on a Chip 22, no. 3 (2022): 641–51. http://dx.doi.org/10.1039/d1lc00751c.

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Duzagac, Fahriye, Gloria Saorin, Lorenzo Memeo, Vincenzo Canzonieri, and Flavio Rizzolio. "Microfluidic Organoids-on-a-Chip: Quantum Leap in Cancer Research." Cancers 13, no. 4 (February 10, 2021): 737. http://dx.doi.org/10.3390/cancers13040737.

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Organ-like cell clusters, so-called organoids, which exhibit self-organized and similar organ functionality as the tissue of origin, have provided a whole new level of bioinspiration for ex vivo systems. Microfluidic organoid or organs-on-a-chip platforms are a new group of micro-engineered promising models that recapitulate 3D tissue structure and physiology and combines several advantages of current in vivo and in vitro models. Microfluidics technology is used in numerous applications since it allows us to control and manipulate fluid flows with a high degree of accuracy. This system is an emerging tool for understanding disease development and progression, especially for personalized therapeutic strategies for cancer treatment, which provide well-grounded, cost-effective, powerful, fast, and reproducible results. In this review, we highlight how the organoid-on-a-chip models have improved the potential of efficiency and reproducibility of organoid cultures. More widely, we discuss current challenges and development on organoid culture systems together with microfluidic approaches and their limitations. Finally, we describe the recent progress and potential utilization in the organs-on-a-chip practice.

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Tan, Jianfeng, Xindi Sun, Jianhua Zhang, Huili Li, Jun Kuang, Lulu Xu, Xinghua Gao, and Chengbin Zhou. "Exploratory Evaluation of EGFR-Targeted Anti-Tumor Drugs for Lung Cancer Based on Lung-on-a-Chip." Biosensors 12, no. 8 (August 9, 2022): 618. http://dx.doi.org/10.3390/bios12080618.

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In this study, we used three-dimensional (3D) printing to prepare a template of a microfluidic chip from which a polydimethylsiloxane (PDMS)lung chip was successfully constructed. The upper and lower channels of the chip are separated by a microporous membrane. The upper channel is seeded with lung cancer cells, and the lower channel is seeded with vascular endothelial cells and continuously perfused with cell culture medium. This lung chip can simulate the microenvironment of lung tissue and realize the coculture of two kinds of cells at different levels. We used a two-dimensional (2D) well plate and a 3D lung chip to evaluate the effects of different EGFR-targeting drugs (gefitinib, afatinib, and osimertinib) on tumor cells. The 3D lung chip was superior to the 2D well plate at evaluating the effect of drugs on the NCI-H650, and the results were more consistent with existing clinical data. For primary tumor cells, 3D lung chips have more advantages because they simulate conditions that are more similar to the physiological cell microenvironment. The evaluation of EGFR-targeted drugs on lung chips is of great significance for personalized diagnosis and treatment and pharmacodynamic evaluation.

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Skorodumova, L. O., K. A. Babalyan, R. Sultanov, A. O. Vasiliev, A. V. Govorov, D. Y. Pushkar, E. A. Prilepskaya, et al. "GSTP1, APC and RASSF1 gene methylation in prostate cancer samples: comparative analysis of MS-HRM method and Infinium HumanMethylation450 BeadChip beadchiparray diagnostic value." Biomeditsinskaya Khimiya 62, no. 6 (2016): 708–14. http://dx.doi.org/10.18097/pbmc20166206708.

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There is a clear need in molecular markers for prostate cancer (PC) risk stratification. Alteration of DNA methylation is one of processes that occur during ÐÑ progression. Methylation-sensitive PCR with high resolution melting curve analysis (MS-HRM) can be used for gene methylation analysis in routine laboratory practice. This method requires very small amounts of DNA for analysis. Numerous results have been accumulated on DNA methylation in PC samples analyzed by the Infinium HumanMethylation450 BeadChip (HM450). However, the consistency of MS-HRM results with chip hybridization results has not been examined yet. The aim of this study was to assess the consistency of results of GSTP1, APC and RASSF1 gene methylation analysis in ÐÑ biopsy samples obtained by MS-HRM and chip hybridization. The methylation levels of each gene determined by MS-HRM were statistically different in the group of PC tissue samples and the samples without signs of tumor growth. Chip hybridization data analysis confirmed the results obtained with the MS-HRM. Differences in methylation levels between tumor tissue and histologically intact tissue of each sample determined by MS-HRM and chip hybridization, were consistent with each other. Thus, we showed that the assessment of GSTP1, APC and RASSF1 gene methylation analysis using MS-HRM is suitable for the design of laboratory assays that will differentiate the PC tissue from the tissue without signs of tumor growth.

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Ho, Thai Huu, Jeong-Heon Lee, Rafael Nunez Nateras, Erik P. Castle, Melissa L. Stanton, Richard Wayne Joseph, Alan H. Bryce, et al. "Genome-wide profiling of histone 3 lysine 36 trimethylation in clear cell renal cell carcinoma." Journal of Clinical Oncology 32, no. 4_suppl (February 1, 2014): 464. http://dx.doi.org/10.1200/jco.2014.32.4_suppl.464.

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464 Background: Although the von Hippel-Lindau (VHL) tumor suppressor gene is mutated in 60% of ccRCC, deletion of VHL in mice is insufficient for tumorigenesis. Sequencing of ccRCC tumors identified mutations in SETD2, a histone H3 lysine 36 (H3K36) trimethyltransferase. We hypothesize that loss of SETD2 methyltransferase activity alters the genome wide pattern of H3K36 trimethylation (H3K36me3) in ccRCC, and contributes to the cancer phenotype. Methods: To generate a genome-wide profile of H3K36me3 in frozen nephrectomy samples and RCC cell lines, we optimized a chromatin immunoprecipitation (ChIP) protocol for the isolation of DNA associated with H3K36me3. H3K36me3 is associated with open chromatin and an H3K36me3-specific antibody was used for immunoprecipitation of endogenous H3K36me3-bound DNA. ChIP PCR primers were optimized for active genes, such as actin, glyceraldehyde-3-phosphate dehydrogenase (GAPDH) and a “gene desert” on chromosome 12 (negative control). ChIP libraries were then generated from 3 paired uninvolved kidney and RCC and 2 RCC cell lines. In order to identify H3K36Me3 upregulated regions in uninvolved kidney and RCC, reads from the ChIP sequencing were mapped to the human genome using Burrows-Wheeler Aligner and SICER algorithms. Results: Using ChIP PCR, we found that active genomic regions were enriched 15-30 fold over the negative controls indicating that the quality and yield of immunoprecipitated DNA/chromatin complexes from frozen tissue was sufficient for ChIP sequencing. A preliminary ChIP sequencing analysis of RCC cell lines and frozen ccRCC tissue indicates that H3K36me3 enriched DNA sequences were mapped to exons (31.3%) compared to introns (13.5%, p<0.001), consistent with the role of H3K36me3 in transcription. Conclusions: Genomic regions enriched for H3K36Me3 binding were identified from patient-derived tissue and RCC cell lines. Current efforts are focused on comparing the H3K36me3 profiles between matched tumor and uninvolved kidney ChIP libraries to generate a genome wide map of dysregulated H3K36me3 modifications.

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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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Wang, Dan, Matthew Gust, and Nicholas Ferrell. "Kidney-on-a-Chip: Mechanical Stimulation and Sensor Integration." Sensors 22, no. 18 (September 13, 2022): 6889. http://dx.doi.org/10.3390/s22186889.

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Bioengineered in vitro models of the kidney offer unprecedented opportunities to better mimic the in vivo microenvironment. Kidney-on-a-chip technology reproduces 2D or 3D features which can replicate features of the tissue architecture, composition, and dynamic mechanical forces experienced by cells in vivo. Kidney cells are exposed to mechanical stimuli such as substrate stiffness, shear stress, compression, and stretch, which regulate multiple cellular functions. Incorporating mechanical stimuli in kidney-on-a-chip is critically important for recapitulating the physiological or pathological microenvironment. This review will explore approaches to applying mechanical stimuli to different cell types using kidney-on-a-chip models and how these systems are used to study kidney physiology, model disease, and screen for drug toxicity. We further discuss sensor integration into kidney-on-a-chip for monitoring cellular responses to mechanical or other pathological stimuli. We discuss the advantages, limitations, and challenges associated with incorporating mechanical stimuli in kidney-on-a-chip models for a variety of applications. Overall, this review aims to highlight the importance of mechanical stimuli and sensor integration in the design and implementation of kidney-on-a-chip devices.

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Anada, Takahisa, and Osamu Suzuki. "Size Regulation of Chondrocyte Spheroids Using a PDMS-Based Cell Culture Chip." Journal of Robotics and Mechatronics 25, no. 4 (August 20, 2013): 644–49. http://dx.doi.org/10.20965/jrm.2013.p0644.

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Cartilage self-repair is limited due to a lack of blood supply and the low mitosis rate of chondrocytes. A tissue engineering approach using cells and biomaterials has the potential to treat cartilage injury. Threedimensional cellular aggregates are an excellent model for mimicking condensation and chondrogenic differentiation in vitro. We developed a technique for constructing spheroids utilizing a polydimethylsiloxane (PDMS)-based culture chip. The objective of this study is to determine how the initial cell density on a culture chip affects the chondrogenic ATDC5 cell differentiation. We demonstrate how culture chips having arrays of multicavities are able to generate high numbers of uniform spheroids rapidly and simultaneously with narrow size distribution. Spheroids are collected easily and noninvasively. Higher cell seeding density on the culture chip enhances chondrogenic cell differentiation. These results suggest the usefulness of this chip in engineering 3D cellular constructs with high functionality for tissue engineering.

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Pannekeet, Marja M., Jos B. Mulder, Jan J. Weening, Dirk G. Struijk, Machteld M. Zweers, and Raymond T. Krediet. "Demonstration of Aquaporin-Chip in Peritoneal Tissue of Uremic and Capd Patients." Peritoneal Dialysis International: Journal of the International Society for Peritoneal Dialysis 16, no. 1_suppl (January 1996): 54–57. http://dx.doi.org/10.1177/089686089601601s08.

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Aquaporin-CHIP is a 28 kD channel forming integral membrane protein. It acts as an osmotically driven, water-selective pore. The presence of aquaporin-CHIP has been demonstrated in the proximal tubule in the kidney and in the pleura, as well as in other tissues. During peritoneal dialysis a dissociation between the transport of water and sodium using hyperosmolar solutions has been reported, suggesting the presence of ultrasmall pores. Water channels, like aquaporin-CHIP, could be the morphological equivalent of these pores. We investigated the possible presence of aquaporinCHIP in cryo-sections of peritoneal tissue using affinity purified human anti-CHIP IgG (P. Agre, Baltimore, MD). Peritoneal biopsies (omenta) were obtained at catheter insertion in 2 uremic patients with end-stage renal disease, and at catheter reimplantation of 1 patient treated with continuous ambulatory peritoneal dialysis (CAPD) for two years. Peritoneal tissue obtained at autopsy from 1 patient who had been on CAPD for four years, but in whom CAPD had been discontinued for five months, was also studied. Aquaporin-CHIP antiserum specific staining was found in the endothelial cells of the peritoneal capillaries in all patients. No obvious difference in the intensity of staining was seen between uremic and CAPD patients. This demonstration of aquaporin-CHIP in human peritoneal endothelial cells supports the hypothesis of the existence of ultrasmall pores within the peritoneal membrane. These water channels facilitate the transcellular transport of water, induced by an osmotic gradient, in the absence of sodium transport. It may be the explanation for the dissociation of water and sodium transport that occurs during hyperosmolar solutions. Aquaporin-CHIP is present in human peritoneal endothelial cells in both uremic and CAPD patients. Aquaporin-CHIP may be the morphological equivalent of the ultrasmall pores within the peritoneal membrane.

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van der Helm, Marinke W., Olivier Y. F. Henry, Amir Bein, Tiama Hamkins-Indik, Michael J. Cronce, William D. Leineweber, Mathieu Odijk, et al. "Non-invasive sensing of transepithelial barrier function and tissue differentiation in organs-on-chips using impedance spectroscopy." Lab on a Chip 19, no. 3 (2019): 452–63. http://dx.doi.org/10.1039/c8lc00129d.

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Sthalekar, Chirag C., Yun Miao, and Valencia Joyner Koomson. "Optical Characterization of Tissue Phantoms Using a Silicon Integrated fdNIRS System on Chip." IEEE Transactions on Biomedical Circuits and Systems 11, no. 2 (April 2017): 279–86. http://dx.doi.org/10.1109/tbcas.2016.2586103.

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Morimoto, Y., S. Mori, F. Sakai, and S. Takeuchi. "Human induced pluripotent stem cell-derived fiber-shaped cardiac tissue on a chip." Lab on a Chip 16, no. 12 (2016): 2295–301. http://dx.doi.org/10.1039/c6lc00422a.

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Zhao, Yimu, Naimeh Rafatian, Erika Y. Wang, Nicole T. Feric, Benjamin F. L. Lai, Ericka J. Knee-Walden, Peter H. Backx, and Milica Radisic. "Engineering microenvironment for human cardiac tissue assembly in heart-on-a-chip platform." Matrix Biology 85-86 (January 2020): 189–204. http://dx.doi.org/10.1016/j.matbio.2019.04.001.

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Veldhuizen, Jaimeson, Joshua Cutts, David A. Brafman, Raymond Q. Migrino, and Mehdi Nikkhah. "Engineering anisotropic human stem cell-derived three-dimensional cardiac tissue on-a-chip." Biomaterials 256 (October 2020): 120195. http://dx.doi.org/10.1016/j.biomaterials.2020.120195.

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Lagowala, Dave Anuj, Seoyoung Kwon, Venkataramana K. Sidhaye, and Deok-Ho Kim. "Human microphysiological models of airway and alveolar epithelia." American Journal of Physiology-Lung Cellular and Molecular Physiology 321, no. 6 (December 1, 2021): L1072—L1088. http://dx.doi.org/10.1152/ajplung.00103.2021.

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Human organ-on-a-chip models are powerful tools for preclinical research that can be used to study the mechanisms of disease and evaluate new targets for therapeutic intervention. Lung-on-a-chip models have been one of the most well-characterized designs in this field and can be altered to evaluate various types of respiratory disease and to assess treatment candidates prior to clinical testing. These systems are capable of overcoming the flaws of conventional two-dimensional (2-D) cell culture and in vivo animal testing due to their ability to accurately recapitulate the in vivo microenvironment of human tissue with tunable material properties, microfluidic integration, delivery of precise mechanical and biochemical cues, and designs with organ-specific architecture. In this review, we first describe an overview of currently available lung-on-a-chip designs. We then present how recent innovations in human stem cell biology, tissue engineering, and microfabrication can be used to create more predictive human lung-on-a-chip models for studying respiratory disease. Finally, we discuss the current challenges and future directions of lung-on-a-chip designs for in vitro disease modeling with a particular focus on immune and multiorgan interactions.

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Nolan, Joanne, Oliver M. T. Pearce, Hazel R. C. Screen, Martin M. Knight, and Stefaan W. Verbruggen. "Organ-on-a-Chip and Microfluidic Platforms for Oncology in the UK." Cancers 15, no. 3 (January 19, 2023): 635. http://dx.doi.org/10.3390/cancers15030635.

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Organ-on-chip systems are capable of replicating complex tissue structures and physiological phenomena. The fine control of biochemical and biomechanical cues within these microphysiological systems provides opportunities for cancer researchers to build complex models of the tumour microenvironment. Interest in applying organ chips to investigate mechanisms such as metastatsis and to test therapeutics has grown rapidly, and this review draws together the published research using these microfluidic platforms to study cancer. We focus on both in-house systems and commercial platforms being used in the UK for fundamental discovery science and therapeutics testing. We cover the wide variety of cancers being investigated, ranging from common carcinomas to rare sarcomas, as well as secondary cancers. We also cover the broad sweep of different matrix microenvironments, physiological mechanical stimuli and immunological effects being replicated in these models. We examine microfluidic models specifically, rather than organoids or complex tissue or cell co-cultures, which have been reviewed elsewhere. However, there is increasing interest in incorporating organoids, spheroids and other tissue cultures into microfluidic organ chips and this overlap is included. Our review includes a commentary on cancer organ-chip models being developed and used in the UK, including work conducted by members of the UK Organ-on-a-Chip Technologies Network. We conclude with a reflection on the likely future of this rapidly expanding field of oncological research.

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Roye, Yasmin, Rohan Bhattacharya, Xingrui Mou, Yuhao Zhou, Morgan A. Burt, and Samira Musah. "A Personalized Glomerulus Chip Engineered from Stem Cell-Derived Epithelium and Vascular Endothelium." Micromachines 12, no. 8 (August 16, 2021): 967. http://dx.doi.org/10.3390/mi12080967.

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Progress in understanding kidney disease mechanisms and the development of targeted therapeutics have been limited by the lack of functional in vitro models that can closely recapitulate human physiological responses. Organ Chip (or organ-on-a-chip) microfluidic devices provide unique opportunities to overcome some of these challenges given their ability to model the structure and function of tissues and organs in vitro. Previously established organ chip models typically consist of heterogenous cell populations sourced from multiple donors, limiting their applications in patient-specific disease modeling and personalized medicine. In this study, we engineered a personalized glomerulus chip system reconstituted from human induced pluripotent stem (iPS) cell-derived vascular endothelial cells (ECs) and podocytes from a single patient. Our stem cell-derived kidney glomerulus chip successfully mimics the structure and some essential functions of the glomerular filtration barrier. We further modeled glomerular injury in our tissue chips by administering a clinically relevant dose of the chemotherapy drug Adriamycin. The drug disrupts the structural integrity of the endothelium and the podocyte tissue layers, leading to significant albuminuria as observed in patients with glomerulopathies. We anticipate that the personalized glomerulus chip model established in this report could help advance future studies of kidney disease mechanisms and the discovery of personalized therapies. Given the remarkable ability of human iPS cells to differentiate into almost any cell type, this work also provides a blueprint for the establishment of more personalized organ chip and ‘body-on-a-chip’ models in the future.

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Galateanu, Bianca, Ariana Hudita, Elena Iuliana Biru, Horia Iovu, Catalin Zaharia, Eliza Simsensohn, Marieta Costache, Razvan-Cosmin Petca, and Viorel Jinga. "Applications of Polymers for Organ-on-Chip Technology in Urology." Polymers 14, no. 9 (April 20, 2022): 1668. http://dx.doi.org/10.3390/polym14091668.

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Organ-on-chips (OOCs) are microfluidic devices used for creating physiological organ biomimetic systems. OOC technology brings numerous advantages in the current landscape of preclinical models, capable of recapitulating the multicellular assemblage, tissue–tissue interaction, and replicating numerous human pathologies. Moreover, in cancer research, OOCs emulate the 3D hierarchical complexity of in vivo tumors and mimic the tumor microenvironment, being a practical cost-efficient solution for tumor-growth investigation and anticancer drug screening. OOCs are compact and easy-to-use microphysiological functional units that recapitulate the native function and the mechanical strain that the cells experience in the human bodies, allowing the development of a wide range of applications such as disease modeling or even the development of diagnostic devices. In this context, the current work aims to review the scientific literature in the field of microfluidic devices designed for urology applications in terms of OOC fabrication (principles of manufacture and materials used), development of kidney-on-chip models for drug-toxicity screening and kidney tumors modeling, bladder-on-chip models for urinary tract infections and bladder cancer modeling and prostate-on-chip models for prostate cancer modeling.

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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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Journal articles on the topic 'Tissue-on-chip'

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