Microengineered platforms for characterizing the contractile function of in vitro cardiac models

Wenkun Dou; Manpreet Malhi; Qili Zhao; Li Wang; Zongjie Huang; Junhui Law; Na Liu; Craig A Simmons; Jason T Maynes; Yu Sun

doi:10.1038/s41378-021-00344-0

Microengineered platforms for characterizing the contractile function of in vitro cardiac models

Microsyst Nanoeng. 2022 Feb 28:8:26. doi: 10.1038/s41378-021-00344-0. eCollection 2022.

Authors

Wenkun Dou^#^{1

2}, Manpreet Malhi^#^{2

3}, Qili Zhao⁴, Li Wang⁵, Zongjie Huang¹, Junhui Law¹, Na Liu⁶, Craig A Simmons^{1

7

8}, Jason T Maynes^{2

3

9

10}, Yu Sun^{1

7

11

12}

Affiliations

¹ Department of Mechanical and Industrial Engineering, University of Toronto, Toronto, ON M5S 3G8 Canada.
² Program in Molecular Medicine, The Hospital for Sick Children, Toronto, ON M5G 1X8 Canada.
³ Department of Biochemistry, University of Toronto, Toronto, ON M5S 1A8 Canada.
⁴ Institute of Robotics and Automatic Information System and the Tianjin Key Laboratory of Intelligent Robotics, Nankai University, Tianjin, 300350 China.
⁵ School of Mechanical & Automotive Engineering, Qilu University of Technology (Shandong Academy of Sciences), Jinan, 250353 China.
⁶ School of Mechatronics Engineering and Automation, Shanghai University, Shanghai, 200444 China.
⁷ Institute of Biomedical Engineering, University of Toronto, Toronto, ON M5S 3G9 Canada.
⁸ Translational Biology & Engineering Program, Ted Rogers Centre for Heart Research, Toronto, ON M5G 1M1 Canada.
⁹ Department of Anesthesiology and Pain Medicine, University of Toronto, Toronto, ON M5S 1A8 Canada.
¹⁰ Department of Anesthesia and Pain Medicine, The Hospital for Sick Children, Toronto, ON M5G 1X8 Canada.
¹¹ Department of Electrical and Computer Engineering, University of Toronto, Toronto, ON M5S 3G4 Canada.
¹² Department of Computer Science, University of Toronto, Toronto, ON M5T 3A1 Canada.

^# Contributed equally.

Abstract

Emerging heart-on-a-chip platforms are promising approaches to establish cardiac cell/tissue models in vitro for research on cardiac physiology, disease modeling and drug cardiotoxicity as well as for therapeutic discovery. Challenges still exist in obtaining the complete capability of in situ sensing to fully evaluate the complex functional properties of cardiac cell/tissue models. Changes to contractile strength (contractility) and beating regularity (rhythm) are particularly important to generate accurate, predictive models. Developing new platforms and technologies to assess the contractile functions of in vitro cardiac models is essential to provide information on cell/tissue physiologies, drug-induced inotropic responses, and the mechanisms of cardiac diseases. In this review, we discuss recent advances in biosensing platforms for the measurement of contractile functions of in vitro cardiac models, including single cardiomyocytes, 2D monolayers of cardiomyocytes, and 3D cardiac tissues. The characteristics and performance of current platforms are reviewed in terms of sensing principles, measured parameters, performance, cell sources, cell/tissue model configurations, advantages, and limitations. In addition, we highlight applications of these platforms and relevant discoveries in fundamental investigations, drug testing, and disease modeling. Furthermore, challenges and future outlooks of heart-on-a-chip platforms for in vitro measurement of cardiac functional properties are discussed.

Keywords: Biosensors.

Publication types

Review