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. 2023 Dec 1;7(4):046113. doi: 10.1063/5.0163363

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© 2023 Author(s).

All article content, except where otherwise noted, is licensed under a Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).

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FIG. 4. — FRESH™ printed cardiac tissues exhibit positive chronotropic and inotropic responses to β-adrenergic receptor agonist isoproterenol L-type calcium channel antagonist verapamil. (a) Representative calcium transients from FRESH™ printed cardiac tissue at baseline and exposure to 2.5 μM of isoproterenol. (b) Direct comparison of a single calcium transient for baseline and isoproterenol treated (2.5 μM) shows the characteristic 30%–40% increase in peak amplitude. (c) Spontaneous beat frequency in response to 2.5 μM of isoproterenol reveals comparable chronotropic response in cardiac tissues FRESH™ printed with different commercially available hiPSC-CM lots. (d) Spontaneous beat frequency in response to 2.5 μM of isoproterenol reveals comparable chronotropic response in cardiac tissues FRESH™ printed with different cellular compositions, either with two cell types (hiPSC-CMs and hCFs) or with three cell types (hiPSC-CMs, hiPSC-ECs, and hCFs). (e) Dose response curve of cardiac tissue beat frequency as a function of isoproterenol concentration showing chronotropic response (n = 3). (f) Dose response curves of normalized calcium transient amplitude as a function of normalized beat rate for isoproterenol-treated hiPSC-CM 2D monolayers as compared to FRESH™ 3D printed cardiac tissues (n = 4 for FRESH™ printed tissues and n = 9 wells for iCell monolayers). (g) Direct comparison of a single calcium transient for baseline and verapamil treated (1 μM). (h) Beat frequency and (I) calcium amplitude response to verapamil dosing.