Wireless Acousto-Piezoelectric Conduit with Aligned Nanofibers for Neural Regeneration

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.