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

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


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.

Keywords: GDNF; chondroitinase ABC; drug delivery; nerve conduit; peripheral nerve; silk fibroin.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Chondroitin ABC Lyase / pharmacology*
  • Drug Liberation
  • Fibroins / chemistry*
  • Glial Cell Line-Derived Neurotrophic Factor / pharmacology*
  • Immunohistochemistry
  • Muscles / drug effects
  • Nerve Regeneration / drug effects*
  • Organ Size / drug effects
  • Peripheral Nerves / drug effects
  • Peripheral Nerves / physiology*
  • Rats, Inbred Lew


  • Glial Cell Line-Derived Neurotrophic Factor
  • Fibroins
  • Chondroitin ABC Lyase