Poly(3,4‐ethylenedioxythiophene)‐Based Neural Interfaces for Recording and Stimulation: Fundamental Aspects and In Vivo Applications

Abstract

Next‐generation neural interfaces for bidirectional communication with the central nervous system aim to achieve the intimate integration with the neural tissue with minimal neuroinflammatory response, high spatio‐temporal resolution, very high sensitivity, and readout stability. The design and manufacturing of devices for low power/low noise neural recording and safe and energy‐efficient stimulation that are, at the same time, conformable to the brain, with matched mechanical properties and biocompatibility, is a convergence area of research where neuroscientists, materials scientists, and nanotechnologists operate synergically. The biotic–abiotic neural interface, however, remains a formidable challenge that prompts for new materials platforms and innovation in device layouts. Conductive polymers (CP) are attractive materials to be interfaced with the neural tissue and to be used as sensing/stimulating electrodes because of their mixed ionic‐electronic conductivity, their low contact impedance, high charge storage capacitance, chemical versatility, and biocompatibility. This manuscript reviews the state‐of‐the‐art of poly(3,4‐ethylenedioxythiophene)‐based neural interfaces for extracellular recording and stimulation, focusing on those technological approaches that are successfully demonstrated in vivo. The aim is to highlight the most reliable and ready‐for‐clinical‐use solutions, in terms of materials technology and recording performance, other than spot major limitations and identify future trends in this field.

Flexible Neural Interfaces Based on 3D PEDOT:PSS Micropillar Arrays

“…[51] In particular, the Bode plot indicates a nearly 3-orders-of-magnitute drop of the impedance at low frequency (0.5 Hz) for PEDOT-coated substrates compared to uncoated ones, in agreement with previous findings comparing PEDOT-coated with pristine metallic microelectrodes. [21] The modulus |Z| measured at 1 kHz is commonly used to estimate the thermal noise level of the system during neural recordings [52] and here varies from 900 to 140 Ω (PEDOTcoated Au/PDMS). A_15 and B_15 electrodes showed slightly lower impedance across all the investigated frequency ranges compared to A_30 and B_30 (Figure 3c).…”

“…[19,20] The use of conducting polymers in neuroelectronics has proven effective for increasing the signal-to-noise ratio (SNR) of the recorded signals. [5,21,22] Indeed, conjugated polymers can offer at the same time appropriate mechanical properties, high electrochemical capacitance and mixed ionic-electronic conduction, [23] all desired properties when interfacing electrical devices with living systems. [5] Besides, conjugated polymers conducting properties also offer advantages for stimulation of the neuronal activity, thanks to the larger charge storage capacity and lower charge injection limit when compared to metal electrodes.…”

Layer-by-Layer Assembly Monitored by PEDOT-Polyamine-Based Organic Electrochemical Transistors

“…2,3 During the last decades, the better understanding of mixed ionic/electronic transport properties, the advancement of fabrication techniques, and the innovation in the design and synthesis of novel materials have driven remarkable progress in this field. 4,5 Therefore, several devices such as biosensors, 6 soft actuators, 7 recording and stimulation probes, 8 and organic electrochemical transistors (OECTs) 9 have been developed, allowing for the detection of biomarkers, the recording of electrophysiological signals, and the stimulation of cells, among other interesting applications. 10,11 In OECTs, particularly, source and drain electrodes are connected through an organic semiconducting channel, whose conductivity is modulated by the application of a gate voltage (V G ) through an electrolyte.…”

PEDOT: PSS promotes neurogenic commitment of neural crest-derived stem cells

“…The latter can be exploited for instance to record electrophysiological signals, locally apply current stimuli or deliver drugs, ultimately increasing the functional and biological performance of pristine materials ( Simon et al, 2016 ; Guex et al, 2017 ; Arbring Sjöström et al, 2018 ). Among these, poly (3,4ethylendioxythiopene) polystyrene sulfonate (PEDOT:PSS) carved out a predominant role as an active material in a number of bio-applications, including wearable and stretchable biosensors, neural arrays for in vitro and in vivo applications up to electroactive implantable scaffolds ( Balint et al, 2014 ; Guex et al, 2017 ; Fan et al, 2019 ; Bianchi et al, 2022 ). The success of PEDOT:PSS can be attributed to its excellent electrical properties, i.e., high conductivity (especially upon secondary doping) ( Takano et al, 2012 ), high charge storage capacitance ( Bianchi et al, 2020 ) and mixed ionic/electronic conductance ( Rivnay et al, 2016 ).…”