Chemistry‑Driven Engineering of PEDOT:PSS Hydrogels for Next‑Generation Bioelectronic Interfaces

ABSTRACT Poly(3,4‐ethylenedioxythiophene): polystyrene sulfonate (PEDOT:PSS) hydrogels have emerged as a versatile class of mixed ionic‐electronic conductors for next‐generation bioelectronic interfaces, owing to their unique combination of high conductivity, mechanical compliance, and aqueous processability. This review systematically examines the chemistry‐driven design principles governing PEDOT:PSS hydrogel systems, with particular emphasis on how polymerization strategies, structural organization, and secondary doping regulate their electrical, mechanical, and interfacial properties. Key synthesis approaches, including in situ, oxidative, electrochemical, and solution polymerization, as well as physical fabrication methods such as freeze–thaw processing, ionic liquid gelation, electrospinning, and additive manufacturing, are critically analyzed in the context of network formation and charge transport pathways. The resulting hydrogels exhibit tunable modulus, enhanced conductivity, and robust adhesion, enabling stable performance under dynamic physiological conditions. Emerging applications in wearable and therapeutic bioelectronics, including electrophysiological signal monitoring, multimodal strain and pressure sensing, soft circuits, and therapeutic systems, are highlighted, demonstrating their ability to bridge the mechanical–electrical mismatch between conventional electronics and biological tissues. Despite significant progress, challenges related to long‐term stability, dehydration‐induced drift, acidity, scalability, and standardization remain. Future directions are outlined, focusing on sustainable chemistries and advanced manufacturing strategies to accelerate clinical translation and large‐scale deployment of PEDOT:PSS‐based bioelectronic systems.