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J Tissue Eng Regen Med. 2017 Mar;11(3):733-742. doi: 10.1002/term.1970. Epub 2014 Nov 25.

Delivery of chondroitinase ABC and glial cell line-derived neurotrophic factor from silk fibroin conduits enhances peripheral nerve regeneration.

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Department of Plastic Surgery, University of Pittsburgh, PA, USA.
Department of Biomedical Engineering, Tufts University, Boston, MA, USA.
Department of Plastic and Reconstructive Surgery, Craniofacial Research Centre, Chang Gung Memorial Hospital, College of Medicine, Chang Gung University, Taiwan.
Department of Bioengineering, University of Pittsburgh, PA, USA.
McGowan Institute for Regenerative Medicine, Pittsburgh, PA, USA.


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.


GDNF; chondroitinase ABC; drug delivery; nerve conduit; peripheral nerve; silk fibroin

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