Repair of nerve injury using biological conduit rich in nerve growth factor and nerve fragments

Abstract

Objective To investigate the role of biological conduit containing nerve growth factor (NGF) and nerve fragments in the regeneration and repair process of peripheral nerve injury, in order to provide a theoretical basis for clinical peripheral nerve repair. Methods A rat model of peripheral nerve injury was established. The experimental animals were randomly divided into four groups: control group (A), autogenous adventitial small gap anastomosis plus autologous nerve fragment group (B), autogenous adventitial small gap anastomosis plus NGF and autologous nerve fragment group (C), and biological conduit plus NGF and autogenous nerve fragment group (D). Gross morphology observation, microscopic observation at the anatomical site, and histological observation were conducted. Measurement data are expressed as mean±standard deviation, and analysis of variance was performed to compare myelinated nerve fibers, Schwann cell number, and motor nerve conduction velocity (MNCV) values among the three groups, followed by pairwise comparisons using the LSD-t test. P<0.05 was considered statistically significant. Results In group A, at the 8th week, the sole ulcer appeared to heal spontaneously, and the right lower limb started to show voluntary activity. The rats with plantar ulcer of the lower limb still did not show significant self-healing at the 12th week, and there was no limb activity. The lower limbs of rats in the other groups showed significant self-healing at the 6th week, with spontaneous activity in the right lower limb. At the 12th week, the toe of the right lower extremity of group A rats was still contracted and could not move freely, while most of those in the remaining three groups had activities. In the longitudinal sections, regenerated nerve fibers were observed in the small gap lumens constructed in groups B, C, and D. At 12 weeks after operation, the numbers of myelinated nerve fibers in groups A-D were 22.30±4.66 (per visual field at ×400 magnification), 51.60±4.45, 56.20±4.66, and 59.20±5.81, respectively, and the difference among the four groups was significant (F=298.48, P<0.001). The numbers of Schwann cells in groups A-D were 16.00±2.24 (per visual field at ×400 magnification), 21.00±3.40, 30.20±3.03, and 34.80±3.35, respectively, and the difference among the four groups was significant (F=197.63, P<0.001). At the 12th week after surgery, the MNCV values in groups A-D were 7.57±1.79 (m/s), 11.49±1.12, 13.86±2.03, and 20.16±2.48, respectively, and the difference among the four groups was significant (F=188.80, P<0.001). The number of myelinated nerve fibers, the number of Schwann cells, and MNCV were significantly higher in group D than in groups A-C (t=26.55, 5.45, 2.15, P<0.001, < 0.001, =0.034; t=21.87, 16.05, 5.35, P<0.001; t=23.19, 15.97, 11.60, P<0.001). Conclusion Combined use of autologous nerve fragments and NGF significantly improves the repair of nerve injury in the peripheral nerve regeneration microenvironment, and this finding provides a theoretical basis for clinical repair of peripheral nerve injury. Key words: Biological conduit; Nerve growth factor; Autologous nerve fragment; Peripheral nerve