Figure 4.

Five different phases of nerve regeneration inside a hollow NGC. The phase corresponds to the sequenced phases of Wallerian degeneration and resulting regeneration mechanism. Phase I corresponds to the fluid phase, where the conduit is filled with plasma exudate containing neurotrophic factors and ECM molecules. This phase takes place a few hours after injury. Phase II corresponds to the matrix formation, where fibrin cables are formed along the gap around 1 week after injury. Phase III is the cellular phase, where Schwann cells invade the gap, migrate and proliferate. They tend to align along the fibrin cable, forming the Bands of Bungner. Phase IV is axonal phase, which occurs around 2 weeks after injury. The re-growing immature axons use the biological cues provided by Schwann cells to reach their distal targets. Phase V corresponds to the myelin phase. At this time, around 3 weeks post-injury, Schwann cells shift to a myelinating phenotype and produce myelin which is wrapped around each axon, forming the mature myelinated axons.