Nanofiber-Based Electroactive Interfaces Enabling Coordinated Neuromodulation and Peripheral Nerve Regeneration

Electrical modulation and repair of peripheral nerves rely on high-quality tissue-material bioelectronic interfaces. However, current conductive materials often exhibit unstable conductivity, mechanical mismatch, and limited processability, which compromise their ability to support both structural regeneration and long-term neuromodulation. Here, we fabricate flexible electroactive core-shell nanofibers via a one-step coaxial electrospinning process, consisting of a poly(ε-caprolactone) (PCL) core and a bi-continuous conductive PEDOT:PSS/polyurethane (PEDOT:PSS/PU) shell. This design integrates mechanical compliance, continuous conductivity, and long-term operational stability. The nanofibers can be assembled into flexible bioelectrodes that provide effective stimulation and high-fidelity neural recording in rat sciatic and rhesus median nerves, while minimizing tissue damage typically caused by rigid metal electrodes. When processed into nerve guidance conduits, they bridge nerve gaps and promote axonal elongation, remyelination, and motor functional recovery in a rat sciatic nerve defect model. Overall, this platform enables synergistic structural repair and electrical modulation, offering a promising strategy for developing bioelectronic interfaces for tissue regeneration.