Controlled release of nerve growth factor enhances sciatic nerve regeneration

• Published in: Experimental neurology 2003-11, Vol.184 (1), p.295-303
• Main Authors: Lee, Annie C, Yu, Vivian M, Lowe, James B, Brenner, Michael J, Hunter, Daniel A, Mackinnon, Susan E, Sakiyama-Elbert, Shelly E
• Format: Article
• Language: English
• Subjects: Animals; Biological and medical sciences; Brain-Derived Neurotrophic Factor - pharmacology; Cell Count; Cell Size; Delayed-Action Preparations; Dose-Response Relationship, Drug; Drug delivery; Drug Implants; Fibrin; Fibrin - chemistry; Fibroblast Growth Factor 2 - pharmacology; Heparin; Male; Medical sciences; Nerve Fibers - drug effects; Nerve Fibers - ultrastructure; Nerve Growth Factor - administration & dosage; Nerve Growth Factor - pharmacology; Nerve guide conduit; Nerve Regeneration - drug effects; Neurology; Neurotrophin 3 - pharmacology; Peripheral nerve; Rats; Rats, Wistar; Sciatic Nerve - drug effects; Sciatic Nerve - physiology; Tissue Engineering
• ISSN: 0014-4886; 1090-2430
• DOI: 10.1016/S0014-4886(03)00258-9

Based on previous studies demonstrating the potential of growth factors to enhance peripheral nerve regeneration, we developed a novel growth factor delivery system to provide sustained delivery of nerve growth factor (NGF). This delivery system uses heparin to immobilize NGF and slow its diffusion from a fibrin matrix. This system has been previously shown to enhance neurite outgrowth in vitro, and in this study, we evaluated the ability of this delivery system to enhance nerve regeneration through conduits. We tested the effect of controlled NGF delivery on peripheral nerve regeneration in a 13-mm rat sciatic nerve defect. The heparin-containing delivery system was studied in combination with three doses of NGF (5, 20, or 50 ng/mL) and the results were compared with positive controls (isografts) and negative controls (fibrin alone, NGF alone, and empty conduits). Nerves were harvested at 6 weeks postoperatively for histomorphometric analysis. Axonal regeneration in the delivery system groups revealed a marked dose-dependent effect. The total number of nerve fibers at both the mid-conduit level and in the distal nerve showed no statistical difference for NGF doses at 20 and 50 ng/mL from the isograft (positive control). The results of this study demonstrate that the incorporation of a novel delivery system providing controlled release of growth factors enhances peripheral nerve regeneration and represents a significant contribution toward enhancing nerve regeneration across short nerve gaps.