title: Delivery of chondroitinase ABC and glial cell line-derived neurotrophic factor from silk fibroin conduits enhances peripheral nerve regeneration.
abstract: Nerve conduits are a proven strategy for guiding axon regrowth following injury. This study compares degradable silk-trehalose films containing chondroitinase ABC (ChABC) and/or glial cell line-derived neurotrophic factor (GDNF) loaded within a silk fibroin-based nerve conduit in a rat sciatic nerve defect model. Four groups of silk conduits were prepared, with the following silk-trehalose films inserted into the conduit: (a) empty; (b) 1 µg GDNF; (3) 2 U ChABC; and (4) 1 µg GDNF/2 U ChABC. Drug release studies demonstrated 20% recovery of GDNF and ChABC at 6 weeks and 24 h, respectively. Six conduits of each type were implanted into 15 mm sciatic nerve defects in Lewis rats; conduits were explanted for histological analysis at 6 weeks. Tissues stained with Schwann cell S-100 antibody demonstrated an increased density of cells in both GDNF- and ChABC-treated groups compared to empty control conduits (p < 0.05). Conduits loaded with GDNF and ChABC also demonstrated higher levels of neuron-specific PGP 9.5 protein when compared to controls (p < 0.05). In this study we demonstrated a method to enhance Schwann cell migration and proliferation and also foster axonal regeneration when repairing peripheral nerve gap defects. Silk fibroin-based nerve conduits possess favourable mechanical and degradative properties and are further enhanced when loaded with ChABC and GDNF. Copyright © 2014 John Wiley & Sons, Ltd.
authors.affiliation: Department of Plastic Surgery, University of Pittsburgh, PA, USA.
authors.forename: Wesley N
authors.initials: WN
authors.lastname: Sivak
authors.affiliation: Department of Biomedical Engineering, Tufts University, Boston, MA, USA.
authors.forename: James D
authors.initials: JD
authors.lastname: White
authors.affiliation: Department of Plastic Surgery, University of Pittsburgh, PA, USA.
authors.forename: Jacqueline M
authors.initials: JM
authors.lastname: Bliley
authors.affiliation: Department of Biomedical Engineering, Tufts University, Boston, MA, USA.
authors.forename: Lee W
authors.initials: LW
authors.lastname: Tien
authors.affiliation: Department of Plastic Surgery, University of Pittsburgh, PA, USA.|Department of Plastic and Reconstructive Surgery, Craniofacial Research Centre, Chang Gung Memorial Hospital, College of Medicine, Chang Gung University, Taiwan.
authors.forename: Han Tsung
authors.initials: HT
authors.lastname: Liao
authors.affiliation: Department of Biomedical Engineering, Tufts University, Boston, MA, USA.
authors.forename: David L
authors.initials: DL
authors.lastname: Kaplan
authors.affiliation: Department of Plastic Surgery, University of Pittsburgh, PA, USA.|Department of Bioengineering, University of Pittsburgh, PA, USA.|McGowan Institute for Regenerative Medicine, Pittsburgh, PA, USA.
authors.forename: Kacey G
authors.initials: KG
authors.lastname: Marra
mesh_terms: D000818:Animals; D019765:Chondroitin ABC Lyase / Q000494:pharmacology*; D065546:Drug Liberation; D005349:Fibroins / Q000737:chemistry*; D051100:Glial Cell Line-Derived Neurotrophic Factor / Q000494:pharmacology*; D007150:Immunohistochemistry; D009132:Muscles / Q000187:drug effects; D009416:Nerve Regeneration / Q000187:drug effects*; D009929:Organ Size / Q000187:drug effects; D010525:Peripheral Nerves / Q000187:drug effects / Q000502:physiology*; D011917:Rats, Inbred Lew
chemical_list: D051100:Glial Cell Line-Derived Neurotrophic Factor; D005349:Fibroins; D019765:Chondroitin ABC Lyase
keywords: GDNF; chondroitinase ABC; drug delivery; nerve conduit; peripheral nerve; silk fibroin