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3D organic bioelectronics for electrical monitoring of human adult stem cells.

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Saez, Janire 
Withers, Aimee 
Barberio, Chiara 


Three-dimensional in vitro stem cell models have enabled a fundamental understanding of cues that direct stem cell fate. While sophisticated 3D tissues can be generated, technology that can accurately monitor these complex models in a high-throughput and non-invasive manner is not well adapted. Here we show the development of 3D bioelectronic devices based on the electroactive polymer poly(3,4-ethylenedioxythiophene)-poly(styrenesulfonate)-(PEDOT:PSS) and their use for non-invasive, electrical monitoring of stem cell growth. We show that the electrical, mechanical and wetting properties as well as the pore size/architecture of 3D PEDOT:PSS scaffolds can be fine-tuned simply by changing the processing crosslinker additive. We present a comprehensive characterization of both 2D PEDOT:PSS thin films of controlled thicknesses, and 3D porous PEDOT:PSS structures made by the freeze-drying technique. By slicing the bulky scaffolds we generate homogeneous, porous 250 μm thick PEDOT:PSS slices, constituting biocompatible 3D constructs able to support stem cell cultures. These multifunctional slices are attached on indium-tin oxide substrates (ITO) with the help of an electrically active adhesion layer, enabling 3D bioelectronic devices with a characteristic and reproducible, frequency dependent impedance response. This response changes drastically when human adipose derived stem cells (hADSCs) grow within the porous PEDOT:PSS network as revealed by fluorescence microscopy. The increase of cell population within the PEDOT:PSS porous network impedes the charge flow at the interface between PEDOT:PSS and ITO, enabling the interface resistance (R1) to be used as a figure of merit to monitor the proliferation of stem cells. The non-invasive monitoring of stem cell growth allows for the subsequent differentiation 3D stem cell cultures into neuron like cells, as verified by immunofluorescence and RT-qPCR measurements. The strategy of controlling important properties of 3D PEDOT:PSS structures simply by altering processing parameters can be applied for development of a number of stem cell in vitro models as well as stem cell differentiation pathways. We believe the results presented here will advance 3D bioelectronic technology for both fundamental understanding of in vitro stem cell cultures as well as the development of personalized therapies.


Acknowledgements: A.S. acknowledges funding from the European Union's Horizon 2020 research and innovation program under the Marie Skłodowska-Curie grant, MultiStem (No. 895801). J.S. acknowledges funding from the European Union's Horizon 2020 research and innovation program under the Marie Skłodowska-Curie grant, ICE-METs (No. 842356). JS also acknowledges the Ikerbasque, Basque Foundation for Science, Departamento de Salud del Gobierno Vasco, FUNDACION Vital Fundazioa, Gobierno de España, Ministerio de Ciencia y Educación de España” under grant PID2020-120313 GB-I00/AIE/10.13039/501100011033, and Gobierno Vasco Dpto. Educación for the consolidation of the research groups (IT1633-22). C.B. and R.M.O. acknowledge funding from the European Research Council (ERC) under the European Union's Horizon 2020 research and innovation programme (grant agreement no. 723951). The authors also wish to acknowledge funding by the Engineering and Physical Sciences Research Council Centre for Doctoral Training in Sensor Technologies and Applications (EP/L015889/1 to CB).


Humans, Electricity, Neurons, Cell Differentiation, Electric Impedance, Adult Stem Cells

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Royal Society of Chemistry (RSC)
European Research Council (723951)
European Commission Horizon 2020 (H2020) Marie Sk?odowska-Curie actions (895801)
Engineering and Physical Sciences Research Council (EP/L015889/1)