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Issue 20, 2016
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Laminar ventricular myocardium on a microelectrode array-based chip

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Abstract

Pharmaceutical screening based on human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) and multi electrode arrays (MEAs) have been proposed as a complementary method for electrophysiological safety and efficacy assessment in drug discovery and development. Contrary to animal models, these cells offer a human genetic background but, at present, fail to recapitulate the mechanical and structural properties of the native human myocardium. Here, we report that topographical cues on soft micromolded gelatin can coax hiPSC-CMs to form laminar cardiac tissues that resemble the native architecture of the heart. Importantly, using this method we were able to record tissue-level electrophysiological responses with a commercially available MEA setup. To validate this platform, we recorded cardiac field potentials at baseline and after pharmacological interventions with a β-adrenergic agonist (isoproterenol). Further, we tested the ability of our system to predict the response of laminar human cardiac tissues to a cardiotoxic pro-drug (terfenadine) and its non-cardiotoxic metabolite (fexofenadine). Finally, we integrated our platform with microfluidic components to build a heart-on-a-chip system that can be fluidically linked with other organs-on-chips in the future.

Graphical abstract: Laminar ventricular myocardium on a microelectrode array-based chip

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Publication details

The article was received on 04 Feb 2016, accepted on 11 Apr 2016 and first published on 13 Apr 2016


Article type: Paper
DOI: 10.1039/C6TB00324A
Citation: J. Mater. Chem. B, 2016,4, 3534-3543
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    Laminar ventricular myocardium on a microelectrode array-based chip

    V. J. Kujala, F. S. Pasqualini, J. A. Goss, J. C. Nawroth and K. K. Parker, J. Mater. Chem. B, 2016, 4, 3534
    DOI: 10.1039/C6TB00324A

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