6
views
0
recommends
+1 Recommend
0 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: not found

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

      Read this article at

      ScienceOpenPublisherPMC
      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          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.

          Related collections

          Author and article information

          Journal
          101128948
          31848
          Lab Chip
          Lab Chip
          Lab on a chip
          1473-0197
          1473-0189
          17 July 2019
          31 January 2017
          01 February 2020
          : 17
          : 3
          : 511-520
          Affiliations
          [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.
          Article
          PMC6995340 PMC6995340 6995340 nihpa845041
          10.1039/c6lc01422d
          6995340
          28092382
          Categories
          Article

          Comments

          Comment on this article