TY - JOUR
T1 - Controlled delivery of glial cell line-derived neurotrophic factor enhances motor nerve regeneration
AU - Moore, Amy M.
AU - Wood, Matthew D.
AU - Chenard, Kristopher
AU - Hunter, Daniel A.
AU - MacKinnon, Susan E.
AU - Sakiyama-Elbert, Shelly E.
AU - Borschel, Gregory H.
N1 - Funding Information:
Funding was provided by the American Association of Plastic Surgery , the American Foundation for Surgery of the Hand , and the American Society for Peripheral Nerve . S.E.S.-E. may receive income based on a license for related technology by the University of Zurich/ETH-Zurich to Kuros Therapeutics. Kuros Therapeutics did not support this research.
PY - 2010/12
Y1 - 2010/12
N2 - Purpose To determine the effect of a motor-specific neurotrophic factor, glial-derived neurotrophic factor (GDNF) on motor nerve regeneration. Methods 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. Results 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. Conclusions 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.
AB - Purpose To determine the effect of a motor-specific neurotrophic factor, glial-derived neurotrophic factor (GDNF) on motor nerve regeneration. Methods 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. Results 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. Conclusions 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.
KW - Biomaterial
KW - Drug delivery
KW - Fibrin
KW - Peripheral nerve injury
KW - Tissue engineering
UR - http://www.scopus.com/inward/record.url?scp=78649931846&partnerID=8YFLogxK
U2 - 10.1016/j.jhsa.2010.08.016
DO - 10.1016/j.jhsa.2010.08.016
M3 - Article
C2 - 21035963
AN - SCOPUS:78649931846
VL - 35
SP - 2008
EP - 2017
JO - Journal of Hand Surgery
JF - Journal of Hand Surgery
SN - 0363-5023
IS - 12
ER -