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Delivery of Chondroitinase ABC and Glial-cell Line Derived Neurotrophic Factor from Silk Fibroin-Conduits Enhances Peripheral Nerve Repair
Sivak WN, Liao HT, Tien LW, White JD, Bliley JM, Kaplan DL, Marra KG
University of Pittsburgh
2014-03-14
Presenter: Wesley Sivak
Affidavit:
The above work represents the original work of the resident and his co-authors in the Plastic Surgery Research Laboratory at the University of Pittsburgh
Director Name: Joseph E Losee, MD
Author Category: Resident Plastic Surgery
Presentation Category: Basic Science Research
Abstract Category: Hand
Background: Repair of peripheral nerve defects remains a challenge; our approach involves the controlled-delivery neurotrophic factors from degradable nerve conduits. The aim of this study was to compare the performance of degradable silk/trehalose films containing chondroitinase ABC (ChABC) and/or glial-cell derived neurotrophic factor (GDNF) loaded within the distal portion of silk fibroin-based nerve conduit in a rat sciatic nerve defect model.
Methods: Four groups of silk conduits were prepared with silk/trehalose films inserted into the distal half of each conduit: (1) empty, (2) 1 microgram GDNF, (3) 2 Units ChABC, and (4) 1 microgram GDNF/2 Units ChABC. Six conduits of each type were implanted in 15mm sciatic nerve defects in Lewis rats. The rats were followed for 6 weeks and the conduits were explanted and fixed for histological analysis.
Results: Conduits stained with Schwann cell S-100 antibody demonstrated a significantly increased density of cells in both GDNF and ChABC treated groups compared to the control group (p<0.05). Conduits loaded with GDNF and ChABC also demonstrated higher levels of neuron-specific PGP 9.5 protein when compared to empty control conduits (p<0.05). No significant differences in gastrocnemius calf muscle weights were observed.
Conclusion: Silk fibroin-based nerve conduits possess favorable mechanical and degradative properties useful for nerve repair. These conduits are further enhanced when loaded with ChABC and GDNF in a controlled, spatial distribution. In this study we demonstrate a viable method to not only enhance Schwann cell migration and proliferation, but also foster axonal regeneration in the repair of long peripheral nerve defects.
