Combination of Electrospun Nanofiber Sheet Incorporating Methylcobalamin and PGA-Collagen Tube for Treatment of a Sciatic Nerve Defect in a Rat Model.

Abstract

For peripheral nerve defects, autografting is considered the therapeutic gold-standard treatment. However, this procedure leads to donor-site morbidity. While various artificial conduits have been recently developed, treatment outcome has been demonstrated to be poorer than that with autograft. In our previous study using a rat sciatic nerve crush injury model, we demonstrated that the delivery of electrospun nanofiber sheets incorporating methylcobalamin (MeCbl sheet) to the local site of a peripheral nerve injury promoted peripheral nerve regeneration. In this study, we examined the effects of combination therapy using an MeCbl sheet and a polyglycolic acid tube filled with collagen sponge (PGA-c) in a rat model of a 10-mm sciatic nerve defect. The rats were divided into 4 groups: (1) sham group (n = 10); (2) PGA-c group (n = 9), in which the gap was bridged using a PGA-c; (3) PGA-c/Sheet group (n = 8), in which the gap was bridged using a PGA-c wrapped in an MeCbl sheet; and (4) autograft group (n = 10), in which the gap was bridged using a reversed autograft. Motor and sensory function were evaluated, electrophysiological analysis was performed, and histomorphological findings were analyzed at 12 weeks postoperatively. Compared with the PGA-c group, the PGA-c/Sheet group demonstrated significant improvements in the paw-withdrawal threshold expressed as a ratio relative to the contralateral side (mean difference [MD], -1.51; 95% confidence interval [CI], -2.64 to -0.38), terminal latency (MD, -0.86 ms; 95% CI, -1.56 to -0.16 ms), myelinated axon area (MD, 4.97%; 95% CI, 0.14% to 9.80%), proportion of myelinated axons (MD, 8.453%; 95% CI, 0.001% to 16.905%), and g-ratio (MD, -0.018; 95% CI, -0.035 to -0.001). No significant improvements were observed regarding motor function, electrophysiological findings with the exception of terminal latency, and axon numbers. An MeCbl sheet in combination with a PGA-c significantly accelerated recovery with respect to sensory function, electrophysiology, and histomorphometry. An MeCbl sheet may represent an effective therapeutic strategy for promoting regeneration across a nerve gap bridged with an artificial conduit.