Decellularized Graft for Repairing Severe Peripheral Nerve Injuries in Sheep

Abstract

BACKGROUND AND OBJECTIVES: Peripheral nerve injuries resulting in a nerve defect require surgical repair. The gold standard of autograft (AG) has several limitations, and therefore, new alternatives must be developed. The main objective of this study was to assess nerve regeneration through a long gap nerve injury (50 mm) in the peroneal nerve of sheep with a decellularized nerve allograft (DCA). METHODS: A 5-cm long nerve gap was made in the peroneal nerve of sheep and repaired using an AG or using a DCA. Functional tests were performed once a month and electrophysiology and echography evaluations at 6.5 and 9 months postsurgery. Nerve grafts were harvested at 9 months for immunohistochemical and morphological analyses. RESULTS: The decellularization protocol completely eliminated the cells while preserving the extracellular matrix of the nerve. No significant differences were observed in functional tests of locomotion and pain response. Reinnervation of the tibialis anterior muscles occurred in all animals, with some delay in the DCA group compared with the AG group. Histology showed a preserved fascicular structure in both AG and DCA; however, the number of axons distal to the nerve graft was higher in AG than in DCA. CONCLUSION: The decellularized graft assayed supported effective axonal regeneration when used to repair a 5-cm long gap in the sheep. As expected, a delay in functional recovery was observed compared with the AG because of the lack of Schwann cells.

Conductive and alignment-optimized porous fiber conduits with electrical stimulation for peripheral nerve regeneration

“…Peripheral nerve injury (PNI) refers to damage occurring in the peripheral nerve plexus, nerve trunk, or its branches, typically resulting from traumatic factors such as lacerations, motor vehicle accidents, compression injuries, and excessive stretching [ 1 ]. The management of long-distance (over 5 cm) nerve defects poses a significant surgical challenge due to the inability to directly suture nerves [ 2 ]. The current treatment for long-distance nerve defects is autologous nerve transplantation (ANT) [ 3 ].…”

Exploring an innovative decellularization protocol for porcine nerve grafts: a translational approach to peripheral nerve repair

“…Among these, an increasing number of strategies proposes the implantation of “decellularized nerve allografts” characterized by the removal of cellular antigens while maintaining the structure of a native nerve made of extracellular matrix (ECM), basal lamina, and endoneurial tubes. These components promote the regenerative process allowing Schwann cell (SC) proliferation, migration, and axonal elongation ( Contreras et al, 2022 , 2023 ). Furthermore, ECM plays a role as a supportive structure through chemical interaction among SCs by soluble signaling, receptor pathways, and mechanotransduction ( Armstrong et al, 2007 ; Urbanski et al, 2016 ; Prest et al, 2018 ; Xu et al, 2020 ).…”

Commentary: Decellularized Graft for Repairing Severe Peripheral Nerve Injuries in Sheep

“…Sheep models have been described in the literature as efficient and clinically relevant models for long nerve injury. 2 In this study, 3 the authors present a long, large diameter nerve injury model in sheep to examine the efficacy of a decellularized nerve allograft compared with autograft in a 5-cm gap of the peroneal nerve. As such, offering a critical evaluation of an alternative allograft to guide future studies in the realm of decellularization and nerve repair in a large animal model.…”