Biocompatible, Electroactive Hydrogels for Stem Cell Differentiation into 3D Neural Networks
Liwen Wang a, Yannik Hajee b, Mani Diba b, Achilleas Savva a
a Regenerative Bioelectronic Technologies (ReBooT) Group, Section Bioelectronics, Department of Microelectronics, Faculty of EEMCS, Delft University of Technology, Delft, The Netherlands.
b Radboud University Medical Centre, Research Institute for Medical Innovation & Regenerative Biomaterials–Dentistry, Nijmegen, the Netherlands
Proceedings of Bioelectronic Interfaces: Materials, Devices and Applications (CyBioEl)
Limassol, Cyprus, 2024 October 22nd - 25th
Organizers: Eleni Stavrinidou and Achilleas Savva
Oral, Liwen Wang, presentation 043
Publication date: 28th June 2024

Regenerative medicine show huge therapeutic potential for neurodegenerative diseases and conditions of the nervous system (1). Challenging conditions such as central nervous system disorders (2), spinal cord injuries (3,4), and peripheral nerve malfunctions could potentially be treated by controlling neuron regeneration via stem cells, as recently has been proven in the clinic (5). At this stage, our understanding of stem cell development and neurogenic differentiation remains limited. There is an urgent need for advanced in vitro platforms for understanding these crucial stem cell properties to support further exploitation in the clinic. Here, we show the development of conducting hydrogels and their use as a 3D  in vitro bioelectronic platform to study the development of neural networks from human induced pluripotent stem cells (iPSCs). Taking advantage of the unique solution mixing properties of conducting polymers (6), we combined PEDOT:PSS (7) with extracellular matrix materials (ECM) to synthesize biocompatible, conductive and transparent hydrogels under physiological conditions. While the in vivo microenvironment for 3D neural networks is replicated, the gels were also mechanical compatible with neural tissue as well electrically active. The transmittance of the hydrogel is found to approximately 50% in the optical spectra range of 300-800 nm for thickness at 400 μm. Detailed electrochemical characterization via impedance spectroscopy and cyclic voltammetry  revealed that PEDOT:PSS intercalation within the hydrogel network gives rise to high charge storage capacitance and current. We believe the results presented here pave the way for hydrogel bioelectronics as 3D platforms to monitor, control, and guide stem-cell-to-neuron differentiation with electrical cues.

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