Engineering a Biomimetic Poly(l-lactic acid) Nerve Conduit with Dual-Scale Aligned Topography toward Bridging Large-Gap Peripheral Nerve Injuries.

Biodegradable nerve guidance conduits (NGCs) are compelling alternatives to autografts for repairing severe peripheral nerve injuries. However, a major obstacle in developing effective NGCs is their structural and functional mismatch with repair and regeneration, leading to inadequate neuronal guidance and improper axon dispersion. Herein, we report a biomimetic NGC that replicates the multiscale architecture of native nerves. It features aligned microchannels of clinically relevant lengths and nanotextured walls. The biomimetic topology is fabricated in poly(l-lactic acid) (PLLA) via an integrated forming technique that exploits strain-induced crystallization to control crack propagation. Comprehensive in vitro experiments confirm the exceptional thermal stability, mechanical robustness, and structural integrity of PLLA NGCs. Importantly, the synergistic micro- and nanoscale alignment is critical for directing axon growth and minimizing dispersion. By elucidating this novel fabrication mechanism and demonstrating dual-scale bioinspired architecture, our work establishes a new platform with the potential for large-gap peripheral nerve repair.