Neurons are fundamental to cognitive and motor functions, relying on intricate electrical and chemical signaling. However, neurological diseases such as Parkinson’s, Alzheimer’s, and Amyotrophic Lateral Sclerosis impair neural function, posing a growing challenge due to aging populations and limited regenerative capacity of the nervous system. Advances in induced pluripotent stem cells (iPSCs) have enabled human-derived neuronal models for disease study, while neural interfaces, particularly microelectrode arrays (MEAs), facilitate electrophysiological investigation both in vivo and in vitro.

This thesis explores the use of poly(3,4-ethylenedioxythiophene):poly(styrene sulfonate) (PEDOT:PSS), a conductive polymer with mixed ionic-electronic conductivity, as a superior neural interface for in vitro neuronal cultures. The study addresses three key objectives: (1) elucidating the electrochemical mechanisms underlying PEDOT:PSS’s performance, (2) validating its biocompatibility and functionality in recording neuronal activity, and (3) establishing protocols for neuronal differentiation and maturation on PEDOT:PSS substrates.

First, a scientific literature search was performed to understand the current standing of PEDOT:PSS as a neuronal interface, exploring the different applications and approaches scientific peers have established, and understanding the working mechanisms of the conduction behind their work. This was complemented with the practical experience with PEDOT:PSS, showcasing its biocompatibility and methods to improve conductivity.

Secondly, neuronal recordings in vitro were made to assess the performance of a custom-built PEDOT:PSS-based MEA and the meaning behind the electrophysiological recordings. Data acquisition, pre-processing, and analysis are discussed to understand the results obtained. Key findings include the performance success of the MEA, while also explaining the shortcomings of the implemented processing algorithms.

Lastly, a motor neuron differentiation protocol from iPSCs was established to further investigate the role of PEDOT:PSS in such context for later studies. The success of the protocol was assessed by morphological, functional, and immunostaining assays.

Future directions include optimizing conductivity through acid treatments, integrating PEDOT:PSS into motor neuron maturation protocols, and exploring electrical stimulation and 3D culture systems. This work contributes to the development of advanced bioelectronic tools for neuronal models and engineering.