Potential of an artificial nerve graft containing Schwann cells for the treatment of a 20-mm nerve defect in rats

OBJECTIVE In a previous study, the authors showed that the migration of Schwann cells (SCs) through end-to-side (ETS) neurorrhaphy promotes axonal regrowth within an acellular nerve graft. In the present study, the authors investigated whether a similar strategy using an artificial nerve (AN) would allow reconstruction of a long nerve gap (20 mm) in rats. METHODS Forty-eight 8- to 12-week-old Sprague Dawley rats were divided into control (AN) and experimental (SC migration-induced AN [SCiAN]) groups. Prior to the experiment, the ANs used in the SCiAN group were populated in vivo with SCs over a 4-week period by ETS neurorrhaphy onto the sciatic nerve. In both groups, a 20-mm sciatic nerve defect was reconstructed in an end-to-end fashion using 20-mm ANs. Sections from the nerve graft and distal sciatic nerve in both groups underwent assessments at 4 weeks for SC migration by immunohistochemical analysis and quantitative reverse transcription–polymerase chain reaction. At 16 weeks, axonal elongation was assessed by immunohistochemical analysis, histomorphometry, and electron microscopy. The number of myelinated fibers was counted, the g-ratio was calculated, and myelin sheath thickness and axon diameter were measured. Furthermore, functional recovery was evaluated at 16 weeks using the Von Frey filament test for sensory recovery and by calculating the muscle fiber area for motor recovery. RESULTS The area occupied by SCs at 4 weeks and by axons at 16 weeks was significantly larger in the SCiAN group than in the AN group. Histomorphometric evaluation of the distal sciatic nerve revealed a significantly greater number of axons. At 16 weeks, plantar perception in the SCiAN group was significantly better, demonstrating improvement in sensory function. However, no tibialis anterior muscle motor improvement was observed in either group. CONCLUSIONS The induction of SC migration into an AN by ETS neurorrhaphy is a useful technique for repairing 20-mm nerve defects in rats, with better nerve regeneration and sensory recovery. No motor recovery was observed in either group; however, motor recovery might require a longer period of time than the lifespan of the AN used in this study. Future studies should investigate whether structural and material reinforcement of the AN, to lower its decomposition rate, can improve functional recovery.