Decellularized Graft for Repairing Severe Peripheral Nerve Injuries in Sheep.

Publisher: Lippincott Williams & Wilkins, Inc Country of Publication: United States NLM ID: 7802914 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1524-4040 (Electronic) Linking ISSN: 0148396X NLM ISO Abbreviation: Neurosurgery Subsets: MEDLINE

Publication: 2022- : [Philadelphia] : Lippincott Williams & Wilkins, Inc.
Original Publication: Baltimore, Williams & Wilkins.

Peripheral Nerve Injuries*/surgery ; Peripheral Nerve Injuries*/pathology; Sheep ; Animals ; Peroneal Nerve/injuries ; Schwann Cells ; Transplantation, Autologous/methods ; Muscle, Skeletal/innervation ; Nerve Regeneration/physiology ; Sciatic Nerve/pathology ; Peripheral Nerves/physiology

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.
(Copyright © Congress of Neurological Surgeons 2023. All rights reserved.)

Comment in: Neurosurgery. 2023 Dec 1;93(6):e149-e150. (PMID: 37409799)

Kasper M, Deister C, Beck F, Schmidt CE. Bench-to-bedside lessons learned: commercialization of an acellular nerve graft. Adv Healthc Mater. 2020;9(16):e2000174.
Forden J, Xu QG, Khu KJ, Midha R. A long peripheral nerve autograft model in the sheep forelimb. Neurosurgery. 2011;68(5):1354-1362.
Cai J, Peng X, Nelson KD, Eberhart R, Smith GM. Synergistic improvements in cell and axonal migration across sciatic nerve lesion gaps using bioresorbable filaments and heregulin-beta1. J Biomed Mater Res A. 2004;69(2):247-258.
Moore AM, MacEwan M, Santosa KB, et al. Acellular nerve allografts in peripheral nerve regeneration: a comparative study. Muscle Nerve. 2011;44(2):221-234.
Hundepool CA, Nijhuis TH, Kotsougiani D, Friedrich PF, Bishop AT, Shin AY. Optimizing decellularization techniques to create a new nerve allograft: an in vitro study using rodent nerve segments. Neurosurg Focus. 2017;42(3):e4.
Lovati AB, D'Arrigo D, Odella S, Tos P, Geuna S, Raimondo S. Nerve repair using decellularized nerve grafts in rat models. A review of the literature. Front Cell Neurosci. 2018;12:427.
Philips C, Campos F, Roosens A, Sánchez-Quevedo MDC, Declercq H, Carriel V. Qualitative and quantitative evaluation of a novel detergent-based method for decellularization of peripheral nerves. Ann Biomed Eng. 2018;46(11):1921-1937.
Szynkaruk M, Kemp SW, Wood MD, Gordon T, Borschel GH. Experimental and clinical evidence for use of decellularized nerve allografts in peripheral nerve gap reconstruction. Tissue Eng B Rev. 2013;19(1):83-96.
Nieto-Nicolau N, López-Chicón P, Fariñas O, et al. Effective decellularization of human nerve matrix for regenerative medicine with a novel protocol. Cell Tissue Res. 2021;384(1):167-177.
Immerman I. Allograft nerve reconstruction: the new gold standard?: Commentary on an article by Peter Tang et al.: “No difference in outcomes detected between decellular nerve allograft and cable autograft in rat sciatic nerve defects”. J Bone Joint Surg Am. 2019;101(10):e48.
Atchabahian A, Genden EM, MacKinnon SE, Doolabh VB, Hunter DA. Regeneration through long nerve grafts in the swine model. Microsurgery. 1998;18(6):379-382.
Tos P, Ronchi G, Papalia I, et al. Chapter 4: Methods and protocols in peripheral nerve regeneration experimental research: part I-experimental models. Int Rev Neurobiol. 2009;87:47-79.
Matsuyama T, Midha R, Mackinnon SE, Munro CA, Wong PY, Ang LC. Long nerve allografts in sheep with Cyclosporin A immunosuppression. J Reconstr Microsurg. 2000;16(3):219-225.
Alvites RD, Branquinho MV, Sousa AC, et al. Establishment of a sheep model for hind limb peripheral nerve injury: common peroneal nerve. Int J Mol Sci. 2021;22(3):1401.
Contreras E, Traserra S, Bolívar S, et al. Repair of long peripheral nerve defects in sheep: a translational model for nerve regeneration. Int J Mol Sci. 2023;24(2):1333.
Contreras E, Bolívar S, Nieto-Nicolau N, et al. A novel decellularized nerve graft for repairing peripheral nerve long gap injury in the rat. Cell Tissue Res. 2022a;390(3):355-366.
Kornfeld T, Vogt PM, Radtke C. Nerve grafting for peripheral nerve injuries with extended defect sizes. Wien Med Wochenschr. 2019;169(9-10):240-251.
Roballo KCS, Burns DT, Ghnenis AB, Osimanjiang W, Bushman JS. Long-term neural regeneration following injury to the peroneal branch of the sciatic nerve in sheep. Eur J Neurosci. 2020;52(10):4385-4394.
Herman ZJ, Ilyas AM. Sensory outcomes in digital nerve repair techniques: an updated meta-analysis and systematic review. Hand (N Y). 2020;15(2):157-164.
Safa B, Jain S, Desai MJ, et al. Peripheral nerve repair throughout the body with processed nerve allografts: results from a large multicenter study. Microsurgery. 2020;40(5):527-537.
Tamez-Mata Y, Pedroza-Montoya FE, Martínez-Rodríguez HG, et al. Nerve gaps repaired with acellular nerve allografts recellularized with Schwann-like cells: preclinical trial. J Plast Reconstr Aesthet Surg. 2022;75(1):296-306.
Contreras E, Traserra S, Bolívar S, et al. Repair of long nerve defects with a new decellularized nerve graft in rats and in sheep. Cells. 2022b;11(24):4074.
Strasberg SR, Mackinnon SE, Genden EM, et al. Long-segment nerve allograft regeneration in the sheep model: experimental study and review of the literature. J Reconstr Microsurg. 1996;12(8):529-537.
Radtke C, Allmeling C, Waldmann KH, et al. Spider silk constructs enhance axonal regeneration and remyelination in long nerve defects in sheep. PLoS One. 2011;25:e16990.
Kornfeld T, Nessler J, Helmer C, et al. Spider silk nerve graft promotes axonal regeneration on long distance nerve defect in a sheep model. Biomaterials. 2021;271:120692.
Pedroza-Montoya FE, Tamez-Mata YA, Simental-Mendía M, et al. Repair of ovine peripheral nerve injuries with xenogeneic human acellular sciatic nerves prerecellularized with allogeneic Schwann-like cells: an innovative and promising approach. Regen Ther. 2022;19:131-143.
Hall SM. Regeneration in cellular and acellular autografts in the peripheral nervous system. Neuropathol Appl Neurobiol. 1986;12(1):27-46.
Rodríguez FJ, Verdú E, Ceballos D, Navarro X. Nerve guides seeded with autologous Schwann cells improve nerve regeneration. Exp Neurol. 2000;161(2):571-584.
Gómez N, Cuadras J, Butí M, Navarro X. Histologic assessment of sciatic nerve regeneration following resection and graft or tube repair in the mouse. Restor Neurol Neurosci. 1996;10(4):187-196.
Evans PJ, MacKinnon SE, Midha R, et al. Regeneration across cold preserved peripheral nerve allografts. Microsurgery. 1999;19(3):115-127.

Date Created: 20230615 Date Completed: 20231127 Latest Revision: 20240222

20240222

10.1227/neu.0000000000002572

37319401