Abstract

Engineered nerve guidance conduits (NGCs) have emerged as promising and advanced solutions for severe peripheral nerve transection; however, their clinical values are often limited by the failure to integrate critical regenerative cues, such as topographical guidance, inflammatory modulation, and electrical stimulation in a synergistic manner. Herein, we present a hierarchically structured NGC, engineered by incorporating α -lipoic acid (ALA)-functionalized carbon nanotubes (CNT@A) within a biodegradable poly (D, L-lactide-co-caprolactone) (PLCL) matrix. This ‘all-in-one’ conduit features a unique lumen filled with aligned, dual-sided micropatterned filaments, which provide superior contact guidance and electrical conductivity while establishing a sustained antioxidative niche. In vitro, the micropatterned surfaces promoted the directional migration of Schwann cells and enhanced the polarization of anti-inflammatory macrophages. Transcriptomic profiling revealed the activation of the PI3K-Akt and focal adhesion pathways. In vivo, this innovative conduit exhibited remarkable efficacy in promoting vascularized axonal regeneration, remyelination, and functional recovery in rat models with long sciatic nerve defects, highlighting its clinical potential for nerve repair and offering a scalable, multi-functional platform for broader tissue engineering applications.