A Glial Cell Line Derived Neurotrophic Factor Delivery System Enhances Nerve Regeneration Across Acellular Nerve Allografts
Kasra Tajdaran, MASc1, Matthew D. Wood, PhD2, Molly S. Shoichet, PhD1, Tess Gordon, PhD1, Gregory H. Borschel, MD, FACS, FAAP1.
1University of Toronto, Toronto, ON, Canada, 2University of Washington, Saint Louis, MO, USA.
Acellular nerve allografts (ANA) are used clinically to bridge nerve gaps. We questioned whether the ability of these allografts to support nerve regeneration could be improved by supplementation with key neurotrophic factors. Here we investigated a local drug delivery system (DDS) for glial cell line-derived neurotrophic factor (GDNF) controlled release to implanted ANAs in rats using drug-loaded polymeric microspheres (MS) embedded in a fibrin gel.
In a rat hindlimb nerve gap model, a 10 mm ANA was used to bridge a 5 mm common peroneal (CP) nerve gap. Experimental groups received DDS treatment at both suture sites of the allografts releasing GDNF for either 2 weeks or 4 weeks. In negative control groups, rats received no DDS treatment or empty DDS. Rats receiving nerve isografts served as the positive control group. Eight weeks after repair, nerve regeneration was assessed using retrograde labeling and collecting nerve samples 10 mm distal to the graft for histomorphometric analysis.
The numbers of motor and sensory neurons that regenerated their axons in all the groups with GDNF MS and isograft treatment were indistinguishable. These numbers were significantly higher as compared to the negative control groups. Nerve histology distal to the nerve graft demonstrated increased axon counts. Fiber frequency analysis indicated a shift to larger fiber diameters due to GDNF MS treatment.
The sustained delivery of GDNF to the implanted ANAs achieved in this study demonstrates the promise of this DDS for the management of severe nerve injuries with large nerve defects.
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