Repair of Long Peripheral Nerve Defects in Sheep: A Translational Model for Nerve Regeneration

Abstract

Despite advances in microsurgery, full functional recovery of severe peripheral nerve injuries is not commonly attained. The sheep appears as a good preclinical model since it presents nerves with similar characteristics to humans. In this study, we induced 5 or 7 cm resection in the peroneal nerve and repaired with an autograft. Functional evaluation was performed monthly. Electromyographic and ultrasound tests were performed at 6.5 and 9 months postoperation (mpo). No significant differences were found between groups with respect to functional tests, although slow improvements were seen from 5 mpo. Electrophysiological tests showed compound muscle action potentials (CMAP) of small amplitude at 6.5 mpo that increased at 9 mpo, although they were significantly lower than the contralateral side. Ultrasound tests showed significantly reduced size of tibialis anterior (TA) muscle at 6.5 mpo and partially recovered size at 9 mpo. Histological evaluation of the grafts showed good axonal regeneration in all except one sheep from autograft 7 cm (AG7) group, while distal to the graft there was a higher number of axons than in control nerves. The results indicate that sheep nerve repair is a useful model for investigating long-gap peripheral nerve injuries.

Decellularized Graft for Repairing Severe Peripheral Nerve Injuries in Sheep

“…17,18 Moreover, they are mixed nerves, causing both motor and sensory deficits after injury that can be assessed over time with techniques commonly used in humans. 14,15…”

“…At monthly intervals until 9 months postsurgery (mps), sheep were tested for motor and sensory functional deficits of the operated hindlimb as previously described in detail. 15 Parameters assessed focused on locomotion and foot drop during walking and withdrawal reflex to pinching the skin of the dorsum of the hoof. Each test was scored on a scale from 0 (normal), −1 (partial loss), to −2 (complete loss).…”

“…Sheep are an adequate model to study nerve regeneration because their nerves are more similar to humans than rat nerves, 13 and long gap injuries can be induced and repaired similar to humans. 14,15 In this study, we assessed a novel decellularized nerve graft to repair a 5-cm long gap in the peroneal nerve of sheep compared with the gold standard AG.…”

“…Sheep are an adequate model to study nerve regeneration because their nerves are more similar to humans than rat nerves, 13 and long gap injuries can be induced and repaired similar to humans. 14,15…”

Mesenchymal Stem Cells in Nerve Tissue Engineering: Bridging Nerve Gap Injuries in Large Animals

“…Within this context, several approaches involving various artificial or natural NGCs in combination with different sources of support cells, particularly MSCs, have been reported in the literature. The outcome measurements were evaluated using different types of animal models [33][34][35][36][37][38][39]. As opposed to small animal models, large animal experimental models provide a critical and comparable microenvironment to that of human nerve injuries and the associated regeneration process.…”