Electroactive scaffolds for spinal cord injury repair: Modulating the electrophysiological homeostasis

Spinal cord injury (SCI) is a devastating neurological disorder characterized by neuronal loss, glial activation, disruption of electrophysiological homeostasis, and disconnection of neural circuits. Increasing evidence indicates that endogenous bioelectrical signaling is a fundamental regulator of neural development, tissue homeostasis, and functional regeneration. Accordingly, reconstruction of the electrophysiological microenvironment has emerged as a promising therapeutic strategy for SCI repair. This review systematically summarizes the dynamic alterations in electrophysiological homeostasis following SCI and discusses how disrupted bioelectrical signaling contributes to impaired neural regeneration. We further provide a comprehensive overview of recent advances in electroactive scaffolds, including conductive, piezoelectric, and magnetoelectric platforms, with emphasis on their electrical activation mechanisms, material characteristics, biological functions, and translational potential. Although conductive, piezoelectric, and magnetoelectric scaffolds employ distinct mechanisms to generate electrical cues, they converge on a common therapeutic strategy of restoring electrophysiological homeostasis through modulation of membrane potential, ion channel activity, and bioelectrical signaling. This coordinated regulation establishes a favorable microenvironment for neural regeneration, ultimately promoting neural circuit reconstruction and functional recovery. Current preclinical studies consistently demonstrate the considerable therapeutic potential of electroactive scaffolds, whereas important challenges remain regarding long-term biosafety, degradation behavior, optimization of stimulation protocols, and clinical translation. Finally, future perspectives are discussed from the standpoint of mechanism-guided scaffold design, intelligent bioelectrical regulation, standardized preclinical evaluation, and multidisciplinary integration. Collectively, this review provides a unified framework for understanding how electroactive scaffolds reconstruct the electrophysiological microenvironment to restore electrophysiological homeostasis, offering new insights into their future clinical translation for SCI repair.