Issue 1, 2020

Engineering anisotropic cardiac monolayers on microelectrode arrays for non-invasive analyses of electrophysiological properties

Abstract

A standard culture of cardiac cells as unorganized monolayers on tissue culture plastic or glass does not recapitulate the architectural or the mechanical properties of native myocardium. We investigated the physical and protein cues from the extracellular matrix to engineer anisotropic cardiac tissues as highly aligned monolayers on top of the microelectrode array (MEA). The MEA platform allows non-invasive measurement of beating rate and conduction velocity. The effect of different extracellular proteins was tested by using the most common extracellular matrix proteins in the heart, fibronectin and gelatin, after aligning myocytes using a microcontact (μC) printing technique. Both proteins showed similar electrophysiological results before the monolayer began to delaminate after the sixth day of culture. Additionally, there were no significant differences on day 4 between the two microcontact printed proteins in terms of sarcomere alignment and gap junction expression. To test the effect of substrate stiffness, a micromolded (μM) gelatin hydrogel was fabricated in different concentrations (20% and 2%), corresponding to the elastic moduli of approximately 33 kPa and 0.7 kPa, respectively, to cover both spectra of the in vivo range of myocardium. Cardiac monolayers under micromolded conditions beat in a much more synchronized fashion, and exhibited conduction velocity that was close to the physiological value. Both concentrations of gelatin hydrogel conditions yielded similar sarcomere alignment and gap junction expression on day 4 of culture. Ultimately, the 3D micromolded gelatin hydrogel that recapitulated myocardial stiffness improved the synchronicity and conduction velocity of neonatal rat ventricular myocytes (NRVM) without any stimulation. Identifying such microenvironmental factors will lead to future efforts to design heart on a chip platforms that mimic in vivo environment and predict potential cardiotoxicity when testing new drugs.

Graphical abstract: Engineering anisotropic cardiac monolayers on microelectrode arrays for non-invasive analyses of electrophysiological properties

Supplementary files

Article information

Article type
Paper
Submitted
15 juil. 2019
Accepted
21 oct. 2019
First published
22 oct. 2019

Analyst, 2020,145, 139-149

Engineering anisotropic cardiac monolayers on microelectrode arrays for non-invasive analyses of electrophysiological properties

A. Alassaf, G. Tansik, V. Mayo, L. Wubker, D. Carbonero and A. Agarwal, Analyst, 2020, 145, 139 DOI: 10.1039/C9AN01339C

To request permission to reproduce material from this article, please go to the Copyright Clearance Center request page.

If you are an author contributing to an RSC publication, you do not need to request permission provided correct acknowledgement is given.

If you are the author of this article, you do not need to request permission to reproduce figures and diagrams provided correct acknowledgement is given. If you want to reproduce the whole article in a third-party publication (excluding your thesis/dissertation for which permission is not required) please go to the Copyright Clearance Center request page.

Read more about how to correctly acknowledge RSC content.

Social activity

Spotlight

Advertisements