Use of Modality-Matched Autogenous Nerve Material in Peripheral Nerve Repair with Conduits

Autologous sensory nerve grafts are often used to repair motor nerve defects, but the impact of these mismatched grafts on regeneration is unclear. Prior work has shown that motor nerve defects repaired with appropriately matched motor nerve grafts are associated with improved regeneration. However, motor nerve sacrifice is likely to be more morbid than sensory nerve loss, so only small motor nerves would be candidates for autologous nerve grafting. Use of nerve conduits is a potential strategy for minimizing the quantity of donor tissue required to successfully incorporate motor nerve elements into motor nerve defects. This study investigated whether modality-matched nerve tissue would improve regeneration through nerve guidance conduits. Forty Lewis rats were randomized to five nerve recontruction groups: 1) reversed tibial nerve autograft (positive control); 2) saline-filled conduit (negative control); 3) conduit containing morselized motor nerve; 4) conduit containing morselized sensory nerve; or 5) conduit containing morselized tibial nerve. At the beginning of the experiment, the motor and sensory branches of femoral and tibial nerves were harvested from isogeneic donor animals for use in conduits. Nerve reconstructions were then performed, and animals were harvested at serial timepoints of 6, 9, and 12 weeks. Results were evaluated by histomorphometric analysis and serial walking-track analysis. It was hypothesized that modality-matching of nerve tissue would optimize regeneration in a conduit-based model. At a 6-week endpoint, regeneration was observed in 25% of saline-filled conduits, 70% of conduits containing nerve fragments, and 100% of isografts. Among the conduits containing nerve fragments, regeneration was observed in 40% of conduits with sensory nerve tissue, 83% of conduits with motor nerve tissue, and 83% of conduits with mixed nerve tissue derived from the tibial nerve. Histomorphometry showed a trend toward improved regeneration at 6 weeks for the groups with motor and mixed nerve fragments. Data from 9 and 12-week endpoints were pending, with further analysis to include motor neuron labeling and serial walking-track analysis. The data suggested that nerve regeneration is significantly enhanced by the inclusion of neural tissue that serves as a “stepping stone” for nerve regeneration through the conduit. This neural tissue potentially simulates the neurotrophic environment of a nerve graft through the contribution of Schwann cells and other neural elements. Further benefit may be associated with the modality-matching of nerve grafts.