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      Current Applications of Organ-on-a-Chip: A Step Closer to Personalized Medicine

      1 , 2 ,
      BIO Integration
      Clinical translation, drug discovery, drug screening, organ-on-a-chip

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          In the pharmaceutical industry, a critical need exists for effective drug development approaches that better account for factors imposed by the physiological microenvironment. Organ-on-a-chip (OOAC)—a revolutionary technology that simulates human organs’ physiological milieu and performance on a chip—has applications in curing illnesses and drug screening, and enormous potential to transform the drug discovery workflow. However, the effective integration of this unique engineering system into ordinary pharmacological and medical contexts remains in development. This Editorial summarizes current research on OOAC systems, and offers insight into future development prospects and the need for a next-generation OOAC framework.

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          Most cited references58

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          Reconstituting organ-level lung functions on a chip.

          Here, we describe a biomimetic microsystem that reconstitutes the critical functional alveolar-capillary interface of the human lung. This bioinspired microdevice reproduces complex integrated organ-level responses to bacteria and inflammatory cytokines introduced into the alveolar space. In nanotoxicology studies, this lung mimic revealed that cyclic mechanical strain accentuates toxic and inflammatory responses of the lung to silica nanoparticles. Mechanical strain also enhances epithelial and endothelial uptake of nanoparticulates and stimulates their transport into the underlying microvascular channel. Similar effects of physiological breathing on nanoparticle absorption are observed in whole mouse lung. Mechanically active "organ-on-a-chip" microdevices that reconstitute tissue-tissue interfaces critical to organ function may therefore expand the capabilities of cell culture models and provide low-cost alternatives to animal and clinical studies for drug screening and toxicology applications.
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            Human gut-on-a-chip inhabited by microbial flora that experiences intestinal peristalsis-like motions and flow.

            Development of an in vitro living cell-based model of the intestine that mimics the mechanical, structural, absorptive, transport and pathophysiological properties of the human gut along with its crucial microbial symbionts could accelerate pharmaceutical development, and potentially replace animal testing. Here, we describe a biomimetic 'human gut-on-a-chip' microdevice composed of two microfluidic channels separated by a porous flexible membrane coated with extracellular matrix (ECM) and lined by human intestinal epithelial (Caco-2) cells that mimics the complex structure and physiology of living intestine. The gut microenvironment is recreated by flowing fluid at a low rate (30 μL h(-1)) producing low shear stress (0.02 dyne cm(-2)) over the microchannels, and by exerting cyclic strain (10%; 0.15 Hz) that mimics physiological peristaltic motions. Under these conditions, a columnar epithelium develops that polarizes rapidly, spontaneously grows into folds that recapitulate the structure of intestinal villi, and forms a high integrity barrier to small molecules that better mimics whole intestine than cells in cultured in static Transwell models. In addition, a normal intestinal microbe (Lactobacillus rhamnosus GG) can be successfully co-cultured for extended periods (>1 week) on the luminal surface of the cultured epithelium without compromising epithelial cell viability, and this actually improves barrier function as previously observed in humans. Thus, this gut-on-a-chip recapitulates multiple dynamic physical and functional features of human intestine that are critical for its function within a controlled microfluidic environment that is amenable for transport, absorption, and toxicity studies, and hence it should have great value for drug testing as well as development of novel intestinal disease models.
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              Development of an enhanced human gastrointestinal epithelial culture system to facilitate patient-based assays.

              The technology for the growth of human intestinal epithelial cells is rapidly progressing. An exciting possibility is that this system could serve as a platform for individualised medicine and research. However, to achieve this goal, human epithelial culture must be enhanced so that biopsies from individuals can be used to reproducibly generate cell lines in a short time frame so that multiple, functional assays can be performed (ie, barrier function and host-microbial interactions).

                Author and article information

                BIO Integration
                Compuscript (Ireland )
                December 2022
                23 December 2022
                : 3
                : 4
                : 143-150
                [1] 1Department of Biomedical Engineering, McMaster University, Hamilton, Ont., Canada
                [2] 2Current affiliation: Arranta Bio, Watertown, MA, USA
                Author notes
                *Correspondence to: Amanda Victorious, E-mail: victoriousamanda@ 123456gmail.com
                Copyright © 2022 The Authors

                This is an open access article distributed under the terms of the Creative Commons Attribution License ( https://creativecommons.org/licenses/by/4.0/). See https://bio-integration.org/copyright-and-permissions/

                Self URI (journal-page): https://bio-integration.org/

                Medicine,Molecular medicine,Radiology & Imaging,Biotechnology,Pharmacology & Pharmaceutical medicine,Microscopy & Imaging
                Clinical translation,drug discovery,drug screening,organ-on-a-chip


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