UC San Diego

Brief electrical stimulation (ES) following peripheral nerve repair has emerged as a promising strategy to accelerate axonal regeneration; however, ES may reduce regenerative specificity by increasing axonal mistargeting and inappropriate motor neuron reinnervation. Biomimetic multichannel scaffolds that recapitulate peripheral nerve fascicular architecture provide structural guidance for organized axonal regeneration and may improve the efficacy of ES. This study evaluated whether combining brief ES with a biomimetic multichannel scaffold enhances regeneration following peripheral nerve injury. Thirty-six Fischer 344 rats underwent 1-cm sciatic nerve transection and biomimetic multichannel scaffold implantation. Eighteen animals received intraoperative ES of the proximal nerve stump (6 V, 20 Hz, 110 μs pulses for 10 min). Samples were collected at 1, 3, and 5 weeks for histological and functional analyses. Axons within the proximal nerve, scaffold, and distal nerve were quantified, and gastrocnemius muscle weight was measured as an indicator of target muscle reinnervation. ES significantly increased axonal regeneration within the scaffold at week 1 (124 ± 31 vs. 38 ± 5 axons; p = 0.0141). At week 3, scaffold + ES significantly increased distal nerve axons (117 ± 21 vs. 19 ± 4; p = 0.0010). At week 5, ES treated animals had greater gastrocnemius muscle weight (0.332 ± 0.010 vs. 0.273 ± 0.015 g; p = 0.0155). These findings demonstrate a temporal progression of enhanced regeneration following combined ES and biomimetic multichannel scaffold implantation, with early axonal growth, subsequent distal nerve regeneration, and improved target muscle retention.