Methods: Regeneration of the sciatic nerve was assessed in C57-black-6 mice. Under general anaesthesia (2-3% Isoflurane) the nerve was sectioned and repaired using 4 epineurial sutures. In five groups (10 animals/group) a scar-reducing agent was injected into and around the proximal and distal nerve stumps; triamcinolone acetonide (1mg/100µL), a Transforming Growth Factor beta inhibitor (TGFßI, Renovo; 5.64 and 16.92mg/100µL), and a scar-reducing peptide (Renovo; 125ng and 500ng/100µL). Another group had 100µL of phosphate buffered saline (PBS) injected alone, and comparisons were also made with a sham-operated control group. After 6 weeks the extent of regeneration was assessed electrophysiologically by determining the ratio of the compound action potential (CAP) modulus evoked by electrical stimulation of the nerve 2mm distal or proximal to the repair site. The percentage area of collagen staining (PAS) at the repair site was analysed using picosirius red and image analysis.
Results: The median CAP ratio in the high dose TGFßI group was 0.44, which was significantly higher than in the PBS carrier group (0.25, p=0.012: Kruskal-Wallis with Conover-Inman multiple comparisons test). None of the other treated groups were different from the carrier, and all had significantly lower ratios than the sham controls (p<0.05). All repair groups had a higher PAS for collagen than sham controls. There was an inverse correlation between the level of scarring and the extent of regeneration.
Conclusions: These results confirm that the extent of regeneration after nerve repair is dependent upon the level of scarring. Administration of a high dose of TGFßI to the repair site appears to result in better regeneration of the damaged axons.