Abstract

Electrical stimulation for application in tissue engineering and regenerative medicine has received increasing attention in recent years. A variety of stimulation methods, waveforms and amplitudes have been studied. However, a clear choice of optimal stimulation parameters is still not available and is complicated by ambiguous reporting standards. In order to understand underlying cellular mechanisms affected by the electrical stimulation, the knowledge of the actual prevailing field strength or current density is required. Here, we present a comprehensive digital representation, a digital twin, of a basic electrical stimulation device for the electrical stimulation of cells in vitro. The effect of electrochemical processes at the electrode surface was experimentally characterised and integrated into a numerical model of the electrical stimulation. Uncertainty quantification techniques were used to identify the influence of model uncertainties on relevant observables. Different stimulation protocols were compared and it was assessed if the information contained in the monitored stimulation pulses could be related to the stimulation model. We found that our approach permits to model and simulate the recorded rectangular waveforms such that local electric field strengths become accessible. Moreover, we could predict stimulation voltages and currents reliably. This enabled us to define a controlled stimulation setting and to identify significant temperature changes of the cell culture in the monitored voltage data. Eventually, we give an outlook on how the presented methods can be applied in more complex situations such as the stimulation of hydrogels or tissue in vivo.

Highlights

  • In recent years, electrical stimulation hasemerged as a possible tool for tissue engineering and regenerative medicine (Balint et al, 2013; da Silva et al, 2020)

  • We study electrical stimulation with direct current as well as rectangular signals using an in vitro stimulation chamber similar to the one introduced for direct current (DC) stimulation in Mobini et al (2016, 2017)

  • Techniques to feed data, which can be recorded in situ, into the theoretical models are introduced

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Summary

Introduction

Electrical stimulation has (re-)emerged as a possible tool for tissue engineering and regenerative medicine (Balint et al, 2013; da Silva et al, 2020). In vitro experiments have been designed to elucidate possible mechanisms of cellular response to electrical stimulation (Zhao et al, 2020). The ever-growing number of publications on in vitro electrical stimulation has been covered in a considerable amount of literature reviews (Funk et al, 2009; Balint et al, 2013; Jahr et al, 2015; Thrivikraman et al, 2018; Chen et al, 2019; da Silva et al, 2020; Ryan et al, 2021)

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