Leveraging Oriented Lateral Walls of Nerve Guidance Conduit with Core–Shell MWCNTs Fibers for Peripheral Nerve Regeneration

Abstract Peripheral nerve regeneration and functional recovery rely on the chemical, physical, and structural properties of nerve guidance conduits (NGCs). However, the limited support for long‐distance nerve regeneration and axonal guidance has hindered the widespread use of NGCs. This study introduces a novel nerve guidance conduit with oriented lateral walls, incorporating multi‐walled carbon nanotubes (MWCNTs) within core‐shell fibers prepared in a single step using a modified electrohydrodynamic (EHD) printing technique to promote peripheral nerve regeneration. The structured conduit demonstrated exceptional stability, mechanical properties, and biocompatibility, significantly enhancing the functionality of NGCs. In vitro cell studies revealed that RSC96 cells adhered and proliferated effectively along the oriented fibers, demonstrating a favorable response to the distinctive architectures and properties. Subsequently, a rat sciatic nerve injury model demonstrated effective efficacy in promoting peripheral nerve regeneration and functional recovery. Tissue analysis and functional testing highlighted the significant impact of MWCNT concentration in enhancing peripheral nerve regeneration and confirming well‐matured aligned axonal growth, muscle recovery, and higher densities of myelinated axons. These findings demonstrate the potential of oriented lateral architectures with coaxial MWCNT fibers as a promising approach to support long‐distance regeneration and encourage directional nerve growth for peripheral nerve repair in clinical applications.