Patterned cardiomyocytes on microelectrode arrays as a functional, high information content drug screening platform

    Authors

    A. Natarajan; M. Stancescu; V. Dhir; C. Armstrong; F. Sommerhage; J. J. Hickman;P. Molnar

    Comments

    Authors: contact us about adding a copy of your work at STARS@ucf.edu

    Abbreviated Journal Title

    Biomaterials

    Keywords

    Biosensor; Cardiac tissue engineering; Cardiomyocyte; Electrode; In; vitro test; Micropatterning; SERUM-FREE MEDIUM; LONG-TERM CULTURE; IN-VITRO; NEURONAL NETWORKS; CARDIAC MYOCYTES; QT PROLONGATION; SURFACES; CELLS; SUBSTRATE; GROWTH; Engineering, Biomedical; Materials Science, Biomaterials

    Abstract

    Cardiac side effects are one of the major causes of drug candidate failures in preclinical drug development or in clinical trials and are responsible for the retraction of several already marketed therapeutics. Thus, the development of a relatively high-throughput, high information content tool to screen drugs and toxins would be important in the field of cardiac research and drug development. In this study, recordings from commercial multielectrode arrays were combined with surface patterning of cardiac myocyte monolayers to enhance the information content of the method; specifically, to enable the measurement of conduction velocity, refractory period after action potentials and to create a functional re-entry model. Two drugs, 1-Heptanol, a gap junction blocker, and Sparfloxacin, a fluoroquinone antibiotic, were tested in this system. 1-Heptanol administration resulted in a marked reduction in conduction velocity, whereas Sparfloxacin caused rapid, irregular and unsynchronized activity, indicating fibrillation. As shown in these experiments, patterning of cardiac myocyte monolayers solved several inherent problems of multielectrode recordings, increased the temporal resolution of conduction velocity measurements, and made the synchronization of external stimulation with action potential propagation possible for refractory period measurements. This method could be further developed as a cardiac side effect screening platform after combination with human cardiomyocytes. (C) 2011 Elsevier Ltd. All rights reserved.

    Journal Title

    Biomaterials

    Volume

    32

    Issue/Number

    18

    Publication Date

    1-1-2011

    Document Type

    Article

    Language

    English

    First Page

    4267

    Last Page

    4274

    WOS Identifier

    WOS:000291171600011

    ISSN

    0142-9612

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