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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.

Author information

1
Department of Plastic Surgery, University of Pittsburgh, PA, USA.
2
Department of Biomedical Engineering, Tufts University, Boston, MA, USA.
3
Department of Plastic and Reconstructive Surgery, Craniofacial Research Centre, Chang Gung Memorial Hospital, College of Medicine, Chang Gung University, Taiwan.
4
Department of Bioengineering, University of Pittsburgh, PA, USA.
5
McGowan Institute for Regenerative Medicine, Pittsburgh, PA, USA.

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.

KEYWORDS:

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

PMID:
25424415
DOI:
10.1002/term.1970
[Indexed for MEDLINE]

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