Pre-degenerated nerve grafts enhance regeneration by shortening the initial delay period

In the present study we tested how nerve grafts with different pre-degeneration periods (1-28 days) influenced the early regenerative response in the rat sciatic nerve. The sciatic nerve on the right side was crushed and after 1-28 days of pre-degeneration, a 10 mm segment was used as an autologous nerve graft and transposed to a freshly made 10 mm long nerve defect on the left side. The regeneration distance was measured by the sensory pinch test 2-10 days after nerve repair. A newly developed mathematical model was used to calculate regeneration rates and initial delay periods from the measured regeneration distances. Pre-degenerated nerve grafts improved nerve regeneration by decreasing the initial delay period as compared to fresh nerve grafts without affecting the regeneration rate. Only one day of pre-degeneration was sufficient to reduce the initial delay period from 3.6 days to 1.7 days. The maximal effect on the initial delay period was achieved after 3 days of pre-degeneration. The initial delay period at later pre-degeneration intervals (7-14 days) was about 1 day. The effect persisted for at least 28 days of pre-degeneration. The regeneration rate was 1.5 mm/day for fresh nerve grafts and between 1.8-2.1 mm/day for pre-degenerated grafts. The results suggest that the effects of pre-degeneration are not only due to the increased cell proliferation in the graft, but that also trophic and/or inflammatory mechanisms may be of importance. Grafts pre-degenerated by crush may have clinical implications since they are easy to perform if an elective nerve grafting procedure is planned.