Purpose: Nerve injuries involving the upper extremity are devastating. Despite recent advances in the understanding of nerve injury and regeneration, functional outcomes remain suboptimal.  The specific aim of this project is to improve motor nerve regeneration, and ultimately function, by providing regenerating motor axons with a motor specific neurotrophic factor, glial cell line-derived neurotrophic factor (GDNF).  To this end, we employ the use of a nerve conduit, a known alternative to autograft repairs, filled with a novel fibrin based delivery system that allows regenerating fibers to have cell mediated exposure to GDNF, to investigate the effects of GDNF on motor nerve regeneration.
Methods: The rat femoral motor nerve model was used to examine the direct effects of the controlled delivery of a GDNF on motor nerve regeneration across a 5 mm nerve gap.  Four experimental groups (n = 7-8) were evaluated. These included GDNF with a fibrin based delivery system (DS), fibrin matrix without growth factor, empty conduits (negative control) and nerve isografts (positive control).  Nerves were harvested 5 weeks after treatment for analysis by histomorphometry and electron microscopy.
Results:  At 5 mm distal to the conduit or isografts, the GDNF group was not significantly different from nerve isografts in the parameters of total nerve fibers, percent neural tissue, and nerve density.  Both the GDNF and isograft groups had significantly more fibers and percent neural tissue than the fibrin matrix alone and empty conduit control groups.  The GDNF group also was significantly more dense than the empty conduit group.  There were no differences among all groups in the parameters of fiber width or myelin width.  On electron microscopy, the GDNF group demonstrated more organized nerve architecture than the control groups. 
Conclusion:  The delivery of GDNF with the fibrin based delivery system enhances nerve regeneration in a femoral motor nerve model.  By optimizing the regenerating microenvironment, this study gives insight into the potential beneficial role of GDNF in the treatment of nerve injuries