Generation and Culture of Cardiac Microtissues in a Microfluidic Chip with a Reversible Open Top Enables Electrical Pacing, Dynamic Drug Dosing and Endothelial Cell Co-Culture

Aisen Vivas*, Camilo IJspeert, Jesper Yue Pan, Kim Vermeul, Albert van den Berg, Robert Passier, Stephan Sylvest Keller, Andries D. van der Meer*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

5 Citations (Scopus)
33 Downloads (Pure)

Abstract

Cardiovascular disease morbidity has increased worldwide. Organs-on-chips and human pluripotent stem cell (hPSC) technologies aid to overcome some of the limitations in cardiac in vitro models. Here, a bi-compartmental, monolithic heart-on-chip device that facilitates porous membrane integration in a single fabrication step is presented. Moreover, the device includes open-top compartments that allow facile co-culture of hPSC-derived cardiomyocytes and human adult cardiac fibroblast into geometrically defined cardiac microtissues. The device can be reversibly closed with a glass seal or a lid with fully customized 3D-printed pyrolytic carbon electrodes allowing electrical stimulation of cardiac microtissues. A subjacent microfluidic channel allowed localized and dynamic drug administration to the cardiac microtissues, as demonstrated by a chronotropic response to isoprenaline. Moreover, the microfluidic channel can also be populated with human induced pluripotent stem-derived endothelial cells allowing co-culture of heterotypic cardiac cells in one device. Overall, this study demonstrates a novel heart-on-chip model that systematically integrates an open-top device with a 3D printed carbon electrode for electrical pacing and culture of cardiac tissues while enabling active perfusion and dynamic drug dosing. Advances in the engineering of human heart-on-chip models represent an important step towards making organ-on-a-chip technology a routine aspect of preclinical cardiac drug development.

Original languageEnglish
Article number2101355
JournalAdvanced Materials Technologies
Volume7
Issue number7
Early online date12 Feb 2022
DOIs
Publication statusPublished - Jul 2022

Keywords

  • carbon electrodes
  • cardiomyocytes
  • drug assays
  • endothelial cells
  • heart-on-chip
  • microfluidics
  • organ-on-chips
  • UT-Hybrid-D

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