Direct Contraction Force Measurements of Engineered Cardiac Tissue Constructs With Inotropic Drug Exposure

Maria Koivisto; Milad Mosallaei; Tarja Toimela; Sampo Tuukkanen; Tuula Heinonen

doi:10.3389/fphar.2022.871569

Direct Contraction Force Measurements of Engineered Cardiac Tissue Constructs With Inotropic Drug Exposure

Front Pharmacol. 2022 May 3:13:871569. doi: 10.3389/fphar.2022.871569. eCollection 2022.

Authors

Maria Koivisto¹, Milad Mosallaei², Tarja Toimela¹, Sampo Tuukkanen², Tuula Heinonen²

Affiliations

¹ FHAIVE (Finnish Hub for Development and Validation of Integrated Approaches), Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland.
² Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland.

Abstract

Contractility is one of the most crucial functions of the heart because it is directly related to the maintenance of blood perfusion throughout the body. Both increase and decrease in contractility may cause fatal consequences. Therefore, drug discovery would benefit greatly from reliable testing of candidate molecule effects on contractility capacity. In this study, we further developed a dual-axis piezoelectric force sensor together with our human cell-based vascularized cardiac tissue constructs for cardiac contraction force measurements. The capability to detect drug-induced inotropic effects was tested with a set of known positive and negative inotropic compounds of isoprenaline, milrinone, omecamtiv mecarbil, propranolol, or verapamil in different concentrations. Both positive and negative inotropic effects were measurable, showing that our cardiac contraction force measurement system including a piezoelectric cantilever sensor and a human cell-based cardiac tissue constructs has the potential to be used for testing of inotropic drug effects.

Keywords: cardiac tissue model; conformal coating; contraction force; force measurement; human-induced pluripotent stem cell–derived cardiomyocytes; in vitro model; inotropic drug.