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      Drug Toxicity Evaluation Based on Organ-on-a-Chip Technology: A Review

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          Abstract

          Organ-on-a-chip academic research is in its blossom. Drug toxicity evaluation is a promising area in which organ-on-a-chip technology can apply. A unique advantage of organ-on-a-chip is the ability to integrate drug metabolism and drug toxic processes in a single device, which facilitates evaluation of toxicity of drug metabolites. Human organ-on-a-chip has been fabricated and used to assess drug toxicity with data correlation with the clinical trial. In this review, we introduced the microfluidic chip models of liver, kidney, heart, nerve, and other organs and multiple organs, highlighting the application of these models in drug toxicity detection. Some biomarkers of toxic injury that have been used in organ chip platforms or have potential for use on organ chip platforms are summarized. Finally, we discussed the goals and future directions for drug toxicity evaluation based on organ-on-a-chip technology.

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          Most cited references111

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          Organoids as an in vitro model of human development and disease.

          The in vitro organoid model is a major technological breakthrough that has already been established as an essential tool in many basic biology and clinical applications. This near-physiological 3D model facilitates an accurate study of a range of in vivo biological processes including tissue renewal, stem cell/niche functions and tissue responses to drugs, mutation or damage. In this Review, we discuss the current achievements, challenges and potential applications of this technique.
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            Acute kidney injury-epidemiology, outcomes and economics.

            Acute kidney injury (AKI) is a widespread problem of epidemic status. Compelling evidence indicates that the incidence of AKI is rapidly increasing, particularly among hospitalized patients with acute illness and those undergoing major surgery. This increase might be partially attributable to greater recognition of AKI, improved ascertainment in administrative data and greater sensitivity of consensus diagnostic and classification schemes. Other causes could be an ageing population, increasing incidences of cardiovascular disease, diabetes mellitus and chronic kidney disease (CKD), and an expanding characterization of modifiable risk factors, such as sepsis, administration of contrast media and exposure to nephrotoxins. The sequelae of AKI are severe and characterized by increased risk of short-term and long-term mortality, incident CKD and accelerated progression to end-stage renal disease. AKI-associated mortality is decreasing, but remains unacceptably high. Moreover, the absolute number of patients dying as a result of AKI is increasing as the incidence of the disorder increases, and few proven effective preventative or therapeutic interventions exist. Survivors of AKI, particularly those who remain on renal replacement therapy, often have reduced quality of life and consume substantially greater health-care resources than the general population as a result of longer hospitalizations, unplanned intensive care unit admissions and rehospitalizations.
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              Organoids-on-a-chip

              Recent studies have demonstrated an array of stem cell–derived, self-organizing miniature organs, termed organoids, that replicate the key structural and functional characteristics of their in vivo counterparts. As organoid technology opens up new frontiers of research in biomedicine, there is an emerging need for innovative engineering approaches for the production, control, and analysis of organoids and their microenvironment. In this Review, we explore organ-on-a-chip technology as a platform to fulfill this need and examine how this technology may be leveraged to address major technical challenges in organoid research. We also discuss emerging opportunities and future obstacles for the development and application of organoid-on-a-chip technology.
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                Author and article information

                Journal
                Micromachines (Basel)
                Micromachines (Basel)
                micromachines
                Micromachines
                MDPI
                2072-666X
                03 April 2020
                April 2020
                : 11
                : 4
                : 381
                Affiliations
                [1 ]State Key Laboratory of Fine Chemicals, Department of Chemical Engineering, Dalian University of Technology, Dalian 116023, China; cyciel96@ 123456163.com
                [2 ]College of Pharmaceutical Science, Soochow University, Suzhou 215123, China; 20194226017@ 123456stu.suda.edu.cn (X.H.); 20194226030@ 123456stu.suda.edu.cn (Y.W.)
                [3 ]Health Science Center, Shenzhen University, Shenzhen 518060, China; chenmond@ 123456foxmail.com (Z.C.); szwzz001@ 123456email.szu.edu.cn (Z.W.); nnjinyu@ 123456sina.com (Y.J.)
                [4 ]Biotechnologhy Division, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian 116023, China; luyao@ 123456dicp.ac.cn
                [5 ]College of Stomatology, Dalian Medical University, Dalian 116011, China; tingjiao@ 123456dmu.edu.cn
                Author notes
                [* ]Correspondence: yluo@ 123456dlut.edu.cn (Y.L.); zhangxl@ 123456suda.edu.cn (X.Z.); Tel.: +86-0411-84986360 (Y.L.)
                Author information
                https://orcid.org/0000-0002-0145-8588
                https://orcid.org/0000-0002-2169-6479
                Article
                micromachines-11-00381
                10.3390/mi11040381
                7230535
                32260191
                9c3e23b3-da00-43df-8249-0601fae93f07
                © 2020 by the authors.

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

                History
                : 01 March 2020
                : 25 March 2020
                Categories
                Review

                organ-on-a-chip,drug toxicity,drug metabolism
                organ-on-a-chip, drug toxicity, drug metabolism

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