Controlled Delivery of Glial Cell Line–Derived Neurotrophic Factor Enhances Motor Nerve Regeneration

Abstract

To determine the effect of a motor-specific neurotrophic factor, glial-derived neurotrophic factor (GDNF) on motor nerve regeneration. We used a nerve conduit filled with a fibrin-based delivery system that provided controlled release of GDNF during nerve regeneration. The motor branch of the rat femoral nerve was used to assess motor nerve regeneration across a 5-mm gap. Four experimental groups (n = 4 to n = 8) were evaluated. These included GDNF with the fibrin-based delivery system (GDNF-DS), fibrin alone, empty conduit (negative control), and nerve isograft (positive control). Nerves were harvested at 5 weeks for analysis by histomorphometry and electron microscopy. At 5 mm distal to the conduit or isografts, the GDNF-DS group was not significantly different from the nerve isograft group in the following histomorphometric measures: total nerve fibers, percentage of neural tissue, and nerve density. Both the GDNF-DS and isograft groups had significantly more fibers and a higher percentage of neural tissue than fibrin alone and empty conduit groups. There were no differences in fiber width among all groups. By electron microscopy, the GDNF-DS and isograft groups also demonstrated more organized nerve architecture than the fibrin alone and empty conduit groups. The delivery of GDNF from the fibrin-based delivery system promotes motor nerve regeneration at a level similar to an isograft in the femoral motor nerve model. This study gives insight into the potential beneficial role of GDNF in the treatment of motor nerve injuries.