Abstract

Organic semiconductors are constantly gaining interest in regenerative medicine. Their tunable physico-chemical properties, including electrical conductivity, are very promising for the control of stem-cell differentiation. However, their use for combined material-based and electrical stimulation remains largely underexplored. Therefore, we carried out a study on whether a platform based on the conductive polymer poly(3,4-ethylenedioxythiophene):polystyrene sulfonate (PEDOT:PSS) can be beneficial to the differentiation of mouse embryonic stem cells (mESCs). The platform was prepared using the layout of a standard 24-well cell-culture plate. Polyethylene naphthalate foil served as the substrate for the preparation of interdigitated gold electrodes by physical vapor deposition. The PEDOT:PSS pattern was fabricated by precise screen printing over the gold electrodes. The PEDOT:PSS platform was able to produce higher electrical current with the pulsed-direct-current (DC) electrostimulation mode (1 Hz, 200 mV/mm, 100 ms pulse duration) compared to plain gold electrodes. There was a dominant capacitive component. In proof-of-concept experiments, mESCs were able to respond to such electrostimulation by membrane depolarization and elevation of cytosolic calcium. Further, the PEDOT:PSS platform was able to upregulate cardiomyogenesis and potentially inhibit early neurogenesis per se with minor contribution of electrostimulation. Hence, the present work highlights the large potential of PEDOT:PSS in regenerative medicine.

Highlights

  • Embryonic stem cells (ESCs) are pluripotent cells derived from the inner cell mass of blastocyst-stage embryos

  • In order to determine the specific role of PEDOT:PSS during electrostimulation, two platform types were prepared in the 24-well-plate format

  • PEDOT:PSS platform was fabricated by screen-printing deposition of PEDOT:PSS paste onto the gold support

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Summary

Introduction

Embryonic stem cells (ESCs) are pluripotent cells derived from the inner cell mass of blastocyst-stage embryos. Other types of stem cells (SCs) are isolated or induced from adult tissues. A plethora of approaches to direct ESCs into a particular cell lineage has been developed for in vitro use. The methods to regulate differentiation could be divided into three groups: biological, chemical and physical [3]. Some growth factors and cytokines are able to stimulate ESCs and accelerate their differentiation. These are, for example, the TGF-beta family of proteins, insulin-like growth factor-1, leukemia inhibitory factor and cardiotrophin-1 [4]. Some chemicals can stimulate differentiation as well. These include dimethyl sulfoxide, 5-Azacytidin or ascorbic acid, as well as exogenous free radicals and reactive oxygen species [3,5].

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