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Related Experiment Video

Updated: Jan 9, 2026

Maturation of Human Stem Cell-derived Cardiomyocytes in Biowires Using Electrical Stimulation
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Asymmetric biphasic electric stimulation supports cardiac maturation and functionality.

Antonio Sileo1, Stefano Gabetti2, Alp Can Gülan1

  • 1Department of Surgery and Department of Biomedicine, University Hospital Basel, University of Basel, Basel, Switzerland.

Journal of Tissue Engineering
|December 1, 2025
PubMed
Summary

This study introduces an asymmetric biphasic electrical stimulation (ES) waveform to improve the maturation of 2D cardiac models. This novel method enhances cellular function and metabolism, creating more physiologically relevant models for cardiotoxicity screening.

Keywords:
asymmetric biphasic waveformbiphasic waveformcardiac tissue engineeringelectrical stimulationmonophasic waveform

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Area of Science:

  • Biomedical Engineering
  • Cardiovascular Research
  • Cellular Physiology

Background:

  • Two-dimensional (2D) cardiac models are crucial for cardiotoxicity screening but often lack the mature structure and function of adult native tissue.
  • Conventional electrical stimulation (ES) methods, like monophasic and symmetric biphasic waveforms, have limitations such as charge accumulation and potential cell hyperpolarization, hindering optimal in vitro maturation.

Purpose of the Study:

  • To introduce and evaluate a novel asymmetric biphasic electrical stimulation (ES) waveform for enhancing the maturation of in vitro cardiac models.
  • To compare the efficacy of the asymmetric biphasic ES waveform against conventional ES protocols in improving cardiac cell function and maturity.

Main Methods:

  • Development of an asymmetric biphasic ES waveform designed to reverse current and minimize residual voltage.
  • Application of the novel ES waveform to neonatal rat cardiac cells.
  • Assessment of electrical functionality, calcium handling, contractility, cellular stress, and metabolic profiles of the stimulated cardiac cells.

Main Results:

  • The asymmetric biphasic ES waveform significantly improved electrical functionality, calcium handling, and contractility of neonatal rat cardiac cells.
  • No cellular stress was observed in cells treated with the asymmetric biphasic ES.
  • Cardiac cells exposed to asymmetric biphasic ES exhibited a metabolic shift towards fatty acid oxidation, characteristic of mature cardiomyocytes.

Conclusions:

  • The asymmetric biphasic ES waveform represents a novel and effective approach for maturing in vitro cardiac models.
  • This method overcomes limitations of conventional ES protocols, offering a promising alternative for generating more physiologically relevant cardiac models for cardiotoxicity screening.