A clinically relevant mouse model for traumatic peripheral nerve injury and repair

In contrast to axons of the central nervous system, peripheral nerve fibers regenerate after traumatic injury, but often not to a clinically satisfactory extent, as only a small proportion of axons achieve long-distance regrowth. While autologous nerve transplantation remains the gold standard for tension-free repair, advances in biomaterials have led to increasing clinical use of synthetic nerve guidance conduits. Despite these developments, experimental research on traumatic peripheral nerve injury (PNI) continues to rely on crush lesions and direct end-to-end repair models, both of which have limited clinical relevance. Here, we present a mouse model of traumatic PNI that closely mimics clinical conditions and enables translationally relevant investigations. Our model combines sciatic nerve transection with conduit-based repair using a commercially available, standardized chitosan nerve guidance conduit that is longitudinally opened prior to implantation. This design allows for the direct application of soluble bioactive compounds to the lesion site. We further detail methods for visualizing and quantifying axonal regeneration at single-fiber resolution within the conduit and provide a time-course analysis of axonal regrowth and macrophage dynamics during Wallerian degeneration by making use of transgenic reporter mice. Functional recovery is assessed using sensory and motor performance tests, and time windows for applying bioactive compounds are defined. Together, this model recapitulates key features of clinical nerve injury and repair, and provides a platform for preclinical testing of regenerative therapies. We propose it as a standardized reference model for experimental PNI research.