Wireless Acousto‐Piezoelectric Conduit with Aligned Nanofibers for Neural Regeneration

Abstract Peripheral nerve injury (PNI) represents a significant clinical challenge, leading to severe motor and sensory dysfunction, as well as irreversible tissue atrophy. Autograft has been commonly utilized as the clinical gold standard; however, it is limited by donor availability and secondary surgery requirements. Here, an ultrasound‐responsive, highly aligned piezoelectric nanofiber nerve guidance conduit (APNF‐NGC) is introduced for peripheral nerve regeneration. Fabricated from electrospun poly‐ l ‐lactic acid (PLLA) nanofibers, the APNF‐NGC features an anisotropically oriented architecture with shear piezoelectricity, providing both structural support and wireless electrical stimulation. The incorporation of polyethylene glycol (PEG) tailors mechanical properties, increases piezoelectric‐phase crystallinity, and improves the surface hydrophilicity, thereby enhancing both biocompatibility and acousto‐piezoelectric response. Finite element analysis and electrical assessment confirm that ultrasound activation of the APNF‐NGC generates an axially oriented electric field, facilitating directional axon elongation. In vivo studies using an 8‐mm sciatic nerve defect rat model demonstrated that the APNF‐NGC achieved nerve reinnervation comparable to that of autografts, as comprehensively validated by behavioral, motor function, and histological evaluations. This dual‐function platform, combining physical guidance with electrical stimulation, presents a promising strategy for neural tissue engineering, offers a potential breakthrough in treating long‐gap PNIs.