Piezoelectric-hydrogen synergy in electrospun oriented fibrous scaffold enables multimodal repair of long-distance peripheral nerve defect.

Functional recovery after long-distance peripheral nerve injury is limited by a poor regenerative microenvironment and slow axonal growth. This study introduces a multifunctional neural scaffold combining topographical, piezoelectric and hydrogen-release strategies. Fabricated via stable jet electrospinning from poly-L-lactic acid, poly(ethylene oxide) and siliconized magnesium (PLLA/PEO/Mg2Si), the oriented fiber scaffold mimics aligned microstructures, provides controllable piezoelectric signals and enables sustained hydrogen delivery. In vitro, it scavenged reactive oxygen species, supported aligned Schwann cell extension and promoted pro-regenerative M2 macrophage polarization. In a rat model with 15 mm sciatic nerve defects, early implantation reduced inflammation, accelerated axonal regeneration and myelination, improved electrophysiological recovery and reduced muscle atrophy. Mechanistically, piezoelectric modulation of the local electrical microenvironment contributed to these effects. By integrating electro-morpho-chemical signaling, this 'piezoelectric-orientation-hydrogen' scaffold offers a promising strategy for repairing long-segment peripheral nerve injuries.