Glial-derived neurotrophic factor (
GDNF) promotes both sensory and motor neuron survival. The delivery of
GDNF to the peripheral nervous system has been shown to enhance regeneration following injury. In this study, we evaluated the effect of affinity-based delivery of
GDNF from a
fibrin matrix in a nerve guidance conduit on nerve regeneration in a 13 mm rat sciatic nerve defect. Seven experimental groups were evaluated which received
GDNF or
nerve growth factor (
NGF) with the delivery system within the conduit, control groups excluding one or more components of the delivery system, and nerve isografts. Nerves were harvested 6 weeks
after treatment for analysis by histomorphometry and electron microscopy. The use of the delivery system (DS) with either
GDNF or
NGF resulted in a higher frequency of nerve regeneration vs. control groups, as evidenced by a neural structure spanning the 13 mm gap. The
GDNF DS and
NGF DS groups were also similar to the nerve isograft group in measures of nerve fiber density, percent neural tissue and myelinated area measurements, but not in terms of total fiber counts. In addition, both groups contained a significantly greater percentage of larger diameter fibers, with
GDNF DS having the largest in comparison to all groups, suggesting more mature neural content. The delivery of
GDNF via the affinity-based delivery system can enhance peripheral nerve regeneration through a
silicone conduit across a critical nerve gap and offers insight into potential future alternatives to the treatment of
peripheral nerve injuries.