title: Controlled release of glial-derived neurotrophic factor from fibrin matrices containing an affinity-based delivery system.
abstract: 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.
authors.affiliation: Department of Biomedical Engineering, Washington University, St. Louis, Missouri 63130, USA.
authors.forename: Matthew D
authors.initials: MD
authors.lastname: Wood
authors.forename: Gregory H
authors.initials: GH
authors.lastname: Borschel
authors.forename: Shelly E
authors.initials: SE
authors.lastname: Sakiyama-Elbert
mesh_terms: D000818:Animals; D002417:Cattle; D002642:Chick Embryo; D003692:Delayed-Action Preparations; D005337:Fibrin / Q000494:pharmacology*; D005727:Ganglia, Spinal / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D051100:Glial Cell Line-Derived Neurotrophic Factor / Q000494:pharmacology*; D006493:Heparin / Q000494:pharmacology; D006801:Humans; D016501:Neurites / Q000187:drug effects / Q000378:metabolism; D010455:Peptides / Q000494:pharmacology; D013552:Swine
chemical_list: D003692:Delayed-Action Preparations; D051100:Glial Cell Line-Derived Neurotrophic Factor; D010455:Peptides; D005337:Fibrin; D006493:Heparin