Abstract
Poly(3,4-ethylenedioxythiophene):poly(styrenesulfonate) (PEDOT:PSS) has become one of the most influential materials in neural engineering, offering high electrical conductivity, mechanical softness, and stable processing in complex aqueous media. Beyond these well-known merits, recent studies indicate that PEDOT:PSS can be regarded as a bio-solid electrolyte interphase (bio-SEI) that governs the interactions between neural probes and biological tissue. In this framework, PEDOT:PSS functions as a selective and adaptive interphase that mediates ion and electron transport, buffers mechanical mismatch, and mitigates chemical or biological degradation at the device-tissue boundary. This review critically summarizes the progress in molecular design, synthesis, and post-treatment strategies that enhance PEDOT:PSS stability and compatibility within physiological environments. Developments such as polydopamine-assisted adhesion, zwitterionic modification, and hybridization with soft hydrogels have expanded its role from a passive coating to an active, self-regulating interphase that prolongs implant performance. We further discuss how the hierarchical structure of PEDOT:PSS—from its molecular organization to device-level morphology—contributes to long-term electrochemical and biological stability. By treating PEDOT:PSS as an intrinsic bio-SEI rather than a simple conductive coating, this perspective highlights its central role in the development of durable, biocompatible, and intelligent neural interfaces for next-generation implantable electronics.