Failed Acellular Nerve Allografts

Abstract

BackgroundAcellular nerve allograft (ANA) occupies an increasingly prominent role in the treatment of peripheral nerve reconstruction. There is demonstrable efficacy; however, some grafts fail to support axonal regrowth and the reasons for this are unclear. This study examines the ANA experience in a specialized peripheral nerve surgery department to discuss the clinical and histological findings in failed cases.MethodFailed ANA grafts were identified from a prospective database using Medical Research Council Classification (MRCC) S3 and M3 as thresholds for success. Cases in which ANA grafting was indicated for nerve related pain and dysesthesia but where no subjective improvement in symptoms occurred were also included. Patients requiring revision surgery after ANA grafting were also considered failures. Cases were then examined in conjunction with a literature review to identify possible mechanisms of failure, including detailed histological analysis in 2 cases.ResultsEight failed procedures were identified from a database of 99 separate allograft records on 74 patients. This included procedures for 2 tibial nerves, 2 superficial radial nerves, 2 median nerves, 1 digital nerve and a lateral cord brachial plexus injury (male/female, 5:3; age range, 24–54 years). Allograft length range 25 to 120 mm. One postoperative infection was identified. Histological findings in 2 cases included adequate vascularization of allograft material without subsequent axonal regeneration, a reduction of large myelinated fibers proximal to a tibial nerve allograft in the setting of a chronic injury, and a preference for small rather than large fiber regeneration.ConclusionsThis article reports instances of ANA graft failure in a variety of contexts, for which the primary reasons for failure remain unclear. The etiology is likely to be multifactorial with both patient, graft and surgeon factors contributing to failure. Further clinical and histological analysis of ANA failures will improve our understanding of the mechanisms of graft failure.

An experimental and numerical study of the microstructural and biomechanical properties of human peripheral nerve endoneurium for the design of tissue scaffolds

“…When ANA is used to repair long or large nerve defects, neural cell necrosis may occur due to insufficient early vascularization, especially when the graft is too thick and revascularization does not reach the center of the graft ( Ray and Mackinnon, 2010 ). Consistent with the results of clinical and fundamental experimental studies, we speculate that ANAs do not form an optimal microenvironment for regeneration ( Thomson et al, 2022 ). The bionic scaffold not only requires sufficient ECM components, but also provide topological guidance by mimicry of microstructure of natural eECM ( Rao et al, 2021 ; Tiwari et al, 2022 ).…”

“…In the literature, another study used allografts to repair nerve defects with gaps of 30–70 mm in the clinic ( Safa and Buncke, 2016 ). Despite these clinical successes, the reason for the limited effectiveness of ANAs in repairing proximal mixed nerve defects remains largely unknown ( Thomson et al, 2022 ).…”

Successful Treatment of a Painful Neuroma Using Fascicular Shifting in the Ulnar Nerve: A Case Report

“…Surgical fascicle ligation has also been described in the treatment of neuroma prevention 2,32 . Nerve defects exceeding several centimeters, which are created upon resection of large neuromas, may be reconstructed using conventional autologous nerve grafts 21 , nerve transfers 22 , nerve conduits 23,24 and processed nerve allografts 5,25,26 . The latter two, in particular, have recently been increasingly used in sensory nerve defects [24][25][26] .…”

“…2 32 Nerve defects exceeding several centimeters, which are created upon resection of large neuromas, may be reconstructed using conventional autologous nerve grafts, 21 nerve transfers, 22 nerve conduits, 23 24 and processed nerve allografts. 5 25 26 The latter two, in particular, have recently been increasingly used in sensory nerve defects. 24 25 26 However, due to the lack of adequate epitopes, nerve conduits are mainly limited to defects of 30 mm, 24 and processed nerve allografts have hardly been applied clinically in nerve defects extending 50 mm.…”

“…24 25 26 However, due to the lack of adequate epitopes, nerve conduits are mainly limited to defects of 30 mm, 24 and processed nerve allografts have hardly been applied clinically in nerve defects extending 50 mm. 25 26 As neuroma treatment does not generally aim for functional restoration, the cost aspect of allografts and conduits also should be considered. Overall, insufficient pain relief and neuroma recurrence are still common findings, 28 keep challenging experts in the field, and novel alternatives are needed.…”