Preclinical evaluation of a novel bilayer collagen nanofiber nerve wrap for accelerating axonal regrowth and myelination in a canine peripheral nerve injury model.

Peripheral nerve injury remains a major clinical challenge due to unsatisfactory functional recovery after severe nerve damage. Although nerve wraps have emerged as a promising strategy for clinical peripheral nerve repair, conventional nerve wraps still exhibit insufficient topographical guidance during regeneration. In this study, we developed a bilayer collagen nanofiber nerve wrap via blow-spinning technology, consisting of an outer random fibrous layer for structural support and an inner aligned nanofibrous layer for longitudinal neural guidance. To further evaluate its regenerative efficacy and translational potential, a canine neurorrhaphy-assisted peripheral nerve repair model was established. The bilayer nanofiber wraps accelerated organized neural tissue remodeling, aligned axonal regeneration, Schwann-cell-associated remodeling and progressive remyelination throughout the regenerative process. Electrophysiological assessment further demonstrated favorable motor nerve conduction recovery, accompanied by improved locomotor restoration and muscle reinnervation. Importantly, the regenerative performance of the bilayer nanofiber wraps was comparable to, and partially superior to, that of a commercially available sponge-like nerve wrap, particularly in promoting oriented neural regeneration and accelerating myelination. These findings highlight the advantages of aligned topographical guidance in promoting organized peripheral nerve regeneration and support the translational potential of the bilayer collagen nerve wrap as a clinically applicable platform for peripheral nerve repair.