Repair of Long Nerve Defects with a New Decellularized Nerve Graft in Rats and in Sheep

Abstract

Decellularized nerve allografts (DC) are an alternative to autografts (AG) for repairing severe peripheral nerve injuries. We have assessed a new DC provided by VERIGRAFT. The decellularization procedure completely removed cellularity while preserving the extracellular matrix. We first assessed the DC in a 15 mm gap in the sciatic nerve of rats, showing slightly delayed but effective regeneration. Then, we assayed the DC in a 70 mm gap in the peroneal nerve of sheep compared with AG. Evaluation of nerve regeneration and functional recovery was performed by clinical, electrophysiology and ultrasound tests. No significant differences were found in functional recovery between groups of sheep. Histology showed a preserved fascicular structure in the AG while in the DC grafts regenerated axons were grouped in small units. In conclusion, the DC was permissive for axonal regeneration and allowed to repair a 70 mm long gap in the sheep nerve.

Decellularized Graft for Repairing Severe Peripheral Nerve Injuries in Sheep

“…19 The only marketed acellular nerve allograft, Avance ® Nerve Graft (Axogen), is indicated for repairing human nerve defects up to 5 cm, but it provides meaningful recovery only in a third of repairs of gaps of 5-7 cm in lower limb nerves. 20 Previous studies in sheep peroneal nerve assaying decellularized allografts in gaps of 3 cm 21 and 7 cm 22 showed effective regeneration, whereas cold-preserved nerve allografts failed to support regeneration along an 8-cm gap. 23 Other assays in sheep used sciatic and tibial nerves repaired with nerve conduits leaving a 6-cm gap 24,25 and with recellularized allografts in a 2-cm gap, 26 with results that were lower but approached those obtained with autologous nerve grafts.…”

Comprehensive ex vivo and in vivo preclinical evaluation of novel chemo enzymatic decellularized peripheral nerve allografts

“…To obtain the sciatic nerves, the animals were deeply anaesthetized by an intraperitoneal injection of acepromazine (Calmo-Neosan ® , Boehringer Ingelheim Animal Health España, S.A.U., Barcelona, Spain, 0.001 mg/g body weight), ketamine (Imalgene 1,000 ® , Merial, Lyon, France, 0.15 mg/g body weight) and atropine (Pfizer, New York, NY, United States, 0.05 μg/g body weight) and then euthanized by an intraperitoneal injection of Eutanex ® solution (0.5 mL/animal). Subsequently, ∼3 cm of both sciatic nerves ( n = 70 nerves) were removed and cryopreserved (10% DMSO in fetal bovine serum at −80°C) until use as previously described ( Chato-Astrain et al, 2020b ; El Soury et al, 2021 ; Garcia-Garcia et al, 2021 ; Contreras et al, 2022 ).…”

“…and atropine (Pfizer, New York, NY, United States, 0.05 μg/g body weight) and then euthanized by an intraperitoneal injection of Eutanex ® solution (0.5 mL/animal). Subsequently, ~3 cm of both sciatic nerves (n = 70 nerves) were removed and cryopreserved (10% DMSO in fetal bovine serum at −80 °C) until use as previously described (Chato-Astrain et al, 2020b;El Soury et al, 2021;Garcia-Garcia et al, 2021;Contreras et al, 2022).…”

“…These tissue-specific 3D natural matrices maintain the complex 3D nerve microarchitecture, the ECM biomolecular composition and the biomechanical integrity of these organs minimizing their immunogenicity ( Gilbert et al, 2006 ; Kneib et al, 2012 ). Moreover DPNAs have several advantages over other tissue-engineered strategies as they can be immediately available for use, they are less expensive than other nerve substitutes, and their use is supported by a growing preclinical and even clinical evidence ( Carriel et al, 2014 ; Lovati et al, 2018 ; Contreras et al, 2022 ; Roballo et al, 2022 ). However, there is variability in the efficacy of the decellularization methods used and currently an ideal procedure does not exist yet.…”

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

“…Previous studies have supported the clinical efficacy of decellularized allografts for peripheral nerve regeneration and repair. 4,5 Thus, this work's contribution to the existing literature is certainly valuable.…”