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      A vascularized and perfused organ-on-a-chip platform for large-scale drug screening applications

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          There is a growing awareness that complex 3-dimensional (3D) organs are not well represented by monolayers of a single cell type – the standard format for many drug screens. To address this deficiency, and with the goal of improving screens so that drugs with good efficacy and low toxicity can be identified, microphysiological systems (MPS) are being developed that better capture the complexity of in vivo physiology. We have previously described an organ-on-a-chip platform that incorporates perfused microvessels, such that survival of the surrounding tissue is entirely dependent on delivery of nutrients through the vessels. Here we describe an arrayed version of the platform that incorporates multiple Vascularized Micro-Organs (VMOs) on a 96-well plate. Each VMO is independently-addressable and flow through the micro-organ is driven by hydrostatic pressure. The platform is easy to use, requires no external pumps or valves, and is highly reproducible. As a proof-of-concept we have created arrayed Vascularized Micro Tumors (VMTs) and used these in a blinded screen to assay a small library of compounds, including FDA-approved anti-cancer drugs, and successfully identified both anti-angiogenic and anti-tumor drugs. This 3D platform is suitable for efficacy/toxicity screening against multiple tissues in a more physiological environment than previously possible.

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          Author and article information

          Lab Chip
          Lab Chip
          Lab on a chip
          17 July 2019
          31 January 2017
          01 February 2020
          : 17
          : 3
          : 511-520
          [a ]Department of Molecular Biology & Biochemistry, University of California, Irvine, CA 92697, USA.
          [b ]Department of Micro/Nano Electronics, Shanghai Jiao Tong University, Shanghai, 200240, China.
          [c ]Department of Biomedical Engineering, University of California, Irvine, CA 92697, USA.
          [d ]Department of Biomedical Engineering, Washington University in St. Louis, MO 63130, USA.
          [e ]Department of Mechanical and Aerospace Engineering, University of California, Irvine, CA 92697, USA.
          [f ]The Edwards Lifesciences Center for Advanced Cardiovascular Technology, Irvine, CA 92697, USA.
          Author notes

          These authors contributed equally to this work.


          These authors contributed equally as senior authors and correspondents to this work.

          Author contributions

          D.T.T.P and X.W designed and implemented the platform, performed experiments, interpreted data, and wrote the manuscript. B.M.C performed experiments, analyzed and interpreted data. A.S contributed knowledge to drug selection and the blind screening experiment. D.Z contributed to finite element simulation and platform microfabrication. J.C.C and L.Y.N.L performed experiments and analyzed data. S.C.G contributed knowledge to project development and edited the manuscript. A.P.L and C.C.W.H conceived the project, interpreted data, and wrote the manuscript. All authors read and approved the manuscript.

          cchughes@ 123456uci.edu ; Fax: +1 (949) 824-8551; Tel: +1 (949) 824-8771. aplee@ 123456uci.edu ; Fax: +1 (949) 824-1727; Tel: +1 (949) 824-9691.
          PMC6995340 PMC6995340 6995340 nihpa845041


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