Multiscale biomimetic design for peripheral nerve repair: Beyond passive bridging

Peripheral nerve injury persists as a formidable clinical challenge, particularly in long-gap and complex lesions where surgical intervention frequently yields suboptimal functional restoration. Current nerve guidance conduits (NGCs) afford limited advantage owing to their passive bridging nature, incapable of recapitulating the native nerve's hierarchical architecture, bioactive microenvironment, or temporally coordinated repair programs. Informed by bibliometric and meta-analytic evidence, this review redefines biomimetic peripheral nerve repair as an orchestrated transition from passive bridging to biologically instructed, adaptive neural interfaces. Departing from a mere enumeration of structural, functional, spatiotemporal, and cross-species biomimicry, each axis is endowed with a specific functional mandate. Structural biomimicry imposes directional and hierarchical guidance, functional biomimicry re-establishes the regenerative niche, spatiotemporal biomimicry synchronizes with stage-dependent repair requirements, and cross-species biomimicry expands the reservoir of transferable design principles. The ways in which these cues converge, compete, or synergize within composite conduits are systematically examined, together with the imperative of prioritizing their configurations for manufacturability, sterilization, regulatory feasibility, and long-gap validation. This synthesis crystallizes a design logic for next-generation NGCs, guiding their evolution from static scaffolds toward adaptive, manufacturable, and clinically translatable regenerative interfaces.