Delivery of chondroitinase ABC and glial cell line-derived neurotrophic factor from silk fibroin conduits enhances peripheral nerve regeneration.
Autor: | Sivak WN; Department of Plastic Surgery, University of Pittsburgh, PA, USA., White JD; Department of Biomedical Engineering, Tufts University, Boston, MA, USA., Bliley JM; Department of Plastic Surgery, University of Pittsburgh, PA, USA., Tien LW; Department of Biomedical Engineering, Tufts University, Boston, MA, USA., Liao HT; 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., Kaplan DL; Department of Biomedical Engineering, Tufts University, Boston, MA, USA., Marra KG; 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. |
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Jazyk: | angličtina |
Zdroj: | Journal of tissue engineering and regenerative medicine [J Tissue Eng Regen Med] 2017 Mar; Vol. 11 (3), pp. 733-742. Date of Electronic Publication: 2014 Nov 25. |
DOI: | 10.1002/term.1970 |
Abstrakt: | 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. (Copyright © 2014 John Wiley & Sons, Ltd.) |
Databáze: | MEDLINE |
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