Reconstruction of Joint‐Associated Peripheral Nerve Defects Using Novel Piezoelectric Spiral‐Structured Poly(Lactic Acid) Fiber Conduits: Regeneration Efficacy and Mechanistic Insights

Abstract Over a million individuals worldwide suffer from peripheral nerve injury annually, while traditional nerve conduits face challenges like poor mechanical adaptability, insufficient bioactivity, and nerve regeneration efficacy. Herein, based on biodegradable poly(lactic acid) (PLA), hydrazide nucleator (HNA) is introduced into PLA fibers to improve its oriented crystallization degree and piezoelectricity, while PLA‐HNA fiber‐based nerve conduits with spiral structure (SNCs) is constructed via further fiber merging, twisting, and coiling process. The spiral geometry of SNCs is systematically optimized to improve its piezoelectric response, mechanical flexibility, and extensibility, significantly surpassing conventional PLA‐based hollow nerve conduits (HNC). Furthermore, SNCs are demonstrated to remarkably enhance Schwann cell proliferation and migration. In vivo studies confirmed that SNCs markedly promoted nerve regeneration, comparable to autologous nerve grafts and surpassing HNC greatly. Notably, SNCs enabled robust regeneration across complex anatomical sites such as joint‐associated and vessel‐crossing nerve defects, where motion usually induced deformation and unstable microenvironments. SNCs implantation restored nerve conduction and muscle responsiveness, enhanced myelination and fiber alignment, and minimized fibrosis. The potential mechanisms underlying SNC‐mediated nerve regeneration are explored, highlighting the mechanical‐electrical coupling advantage of the spiral structure in adapting to dynamic environments, and offering promising therapeutic strategies for PNI repair.