Title

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

Authors

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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