Electroactive Biomaterials Modulating Ion Channels in Nervous System Regeneration

Abstract Traumatic injury to the central and peripheral nervous systems disrupts the electrophysiological microenvironment through persistent ionic dysregulation and maladaptive ion channel remodeling, creating conditions that are fundamentally hostile to endogenous repair. Conventional biomaterials, while offering structural support, remain electrically inert and unable to reconstitute the bioelectric signaling context essential for functional neural regeneration. Here, we review the emerging class of electroactive biomaterials, encompassing conductive and piezoelectric platforms, that are engineered to actively interface with and therapeutically remodel this pathological milieu. We first systematically characterize the electrophysiological sequelae of neurotrauma, detailing how glutamate excitotoxicity, GABAergic polarity inversion, and voltage-gated channel dysfunction collectively drive aberrant depolarized states in both central and peripheral injury contexts. We then analyze how electroactive scaffolds transduce or autonomously generate localized electrical cues to modulate ion channel kinetics and activate neurogenic cascades across brain, spinal cord, and peripheral nerve injury models. Finally, we critically examine translational barriers—including interfacial impedance mismatch, asynchronous biodegradation, and neuroimmune reactivity—that currently impede clinical deployment. This synthesis identifies key design imperatives for next-generation bioelectronic therapies capable of dynamically restoring electrophysiological homeostasis to promote meaningful neural recovery.