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Controlled release of glial‐derived neurotrophic factor from fibrin matrices containing an affinity‐based delivery system
Author(s) -
Wood Matthew D.,
Borschel Gregory H.,
SakiyamaElbert Shelly E.
Publication year - 2008
Publication title -
journal of biomedical materials research part a
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.849
H-Index - 150
eISSN - 1552-4965
pISSN - 1549-3296
DOI - 10.1002/jbm.a.32043
Subject(s) - glial cell line derived neurotrophic factor , neurite , fibrin , biophysics , heparin , materials science , neurotrophic factors , biochemistry , in vitro , pharmacology , chemistry , receptor , biology , immunology
This research evaluated the controlled release of glial‐derived neurotrophic factor (GDNF) from an affinity‐based delivery system (ABDS) as potential treatment for peripheral nerve injury. The ABDS consisted of a bidomain peptide containing a transglutaminase substrate, allowing crosslinking into fibrin matrices, and a heparin‐binding domain based on the antithrombin‐III heparin‐binding domain, heparin, and GDNF, which was sequestered based on its heparin‐binding affinity. The objective of this research was to determine the release rate and biological activity of GDNF released from the ABDS in vitro . The ratio of peptide to heparin was found to modulate the rate of GDNF release. The biological activity of GDNF released from the ABDS was assayed using chick dorsal root ganglia (DRGs) neurite extension. Neurite extension was equivalent for fibrin matrices containing the ABDS for all concentrations of GDNF tested versus DRGs grown with GDNF in the media. Furthermore, neurite extension was enhanced in fibrin matrices containing 100 ng/mL of GDNF with the ABDS versus matrices with GDNF at a simliar dose but no ABDS. These results suggest that GDNF can be retained and released in a biologically activity form from the ABDS, and thus this approach may prove useful for the treatment of peripheral nerve injury. © 2008 Wiley Periodicals, Inc. J Biomed Mater Res, 2009