Flexible bioelectronic electrodes: From engineering strategies to cross-domain biomedical applications

Flexible electrodes have emerged as key bioelectronic interfaces for recording, modulation, and sensing in complex biological environments. Their mechanical compliance, conformal contact, and tunable electrochemical properties enable effective coupling between soft biological tissues and rigid electronic systems. However, the fabrication strategies and interface requirements governing flexible electrode performance differ substantially across biological domains, and this cross-domain design landscape has not been systematically addressed. This review comprehensively examines preparation and optimization strategies for flexible electrodes, covering structure-driven designs, material selection, and surface functionalization approaches targeting charge transfer, selectivity, and biostability. We further survey applications across four biomedical domains: brain interfaces, peripheral nerve interfaces, gastrointestinal tract, and wearable health monitoring, spanning epidermal, visceral, and neural environments in both in vitro and in vivo settings. By mapping design strategies onto diverse biological interface requirements, this review provides a cross-domain reference framework to guide application-specific electrode design. Remaining challenges in scalable fabrication, chronic biointegration, closed-loop operation, and clinical translation are critically discussed, with future directions emphasizing convergence across neuroscience, materials science, and intelligent bioelectronics.