| Injured peripheral nerves have a limited capacity to regenerate. Surgically, severed nerves are repaired using autografts, but it does not result in full functional recovery. In this study we have proposed the use of chitosan nerve guides to bridge the severed nerve ends. Functional nerve repair was evaluated using gait analysis. A significant improvement in functional recovery was seen with chitosan nerve guides. Histologically, chitosan nerve guides exhibited increased axonal growth; however no difference in myelination was noted when compared to the control groups. Thus chitosan nerve guide provided an enclosed environment to promote axonal growth, but it lacked the trophic factors necessary to support axonal extension and re-myelination. To enhance the mechanical and biological properties of the nerve guide, chitosan was blended with collagen. Functional improvement was noted during the stance phase for the chitosan-collagen nerve guides, however full functional recovery was not attained. Histologically, chitosan collagen nerve guides promoted increased axonal sprouting, but were unsuccessful in supporting axonal extension from the proximal to the distal end. However, the axon diameter did increase from the proximal to distal end, indicating that chitosan collagen nerve guides support the development of regenerating axons into mature axons. Similar to the chitosan nerve guides, the chitosan collagen nerve guides, were unable to support myelination. As a result, to enhance the quality of nerve regeneration, chitosan was blended with neurotrophic factor GDNF (GLC) and laminin (LC). Functional gait analysis from the stance phase concluded that functional recovery occurred over time for both GLC and LC groups, but no difference was noted between the GLC and LC groups. Histologically, GLC group provided excellent trophic guidance cues and supported axon maturation. Increased myelination was noted for the GLC group compared to the LC and control groups. Thus GDNF does play an important role in enhancing the myelination of axons. The results of our study conclude that chitosan can be applied as nerve guide if blended with correct proteins and neurotrophic factors to promote and support axon extension and maturation. |
