Acellular Nerve Allografts in Major Peripheral Nerve Repairs: An Analysis of Cases Presenting With Limited Recovery

Abstract

Background: Acellular nerve allografts have been used successfully and with increasing frequency to reconstruct nerve injuries. As their use has been expanded to treat longer gap, larger diameter nerve injuries, some failed cases have been reported. We present the histomorphometry of 5 such cases illustrating these limitations and review the current literature of acellular nerve allografts.

Methods: Between 2014 and 2019, 5 patients with iatrogenic nerve injuries to the median or ulnar nerve reconstructed with an AxoGen AVANCE nerve allograft at an outside hospital were treated in our center with allograft excision and alternative reconstruction. These patients had no clinical or electrophysiological evidence of recovery, and allograft specimens at the time of surgery were sent for histomorphological examination.

Results: Three patients with a median and 2 with ulnar nerve injury were included. Histology demonstrated myelinated axons present in all proximal native nerve specimens. In 2 cases, axons failed to regenerate into the allograft and in 3 cases, axonal regeneration diminished or terminated within the allograft.

Conclusions: The reported cases demonstrate the importance of evaluating the length and the function of nerves undergoing acellular nerve allograft repair. In long length, large-diameter nerves, the use of acellular nerve allografts should be carefully considered.

Keywords: allograft; autograft; basic science; diagnosis; nerve; nerve injury; nerve reconstruction; nerve regeneration.

Figure 1.

Patient 1 with intraoperative findings demonstrating a large proximal neuroma of the median nerve and an 8-cm nerve gap present upon resection of the allograft. Note. The arrows demonstrate the location of the histological sections. Note the abundance of myelinated axons in the median nerve proximal to the coaptation site of the proximal median nerve and the allograft. Note the decrease of myelinated axons across the allograft, as myelinated axons are visible within the midgraft, but only a few myelinated axons present within the distal nerve.

Figure 2.

Patient 2 with intraoperative findings of a large neuroma of the median nerve proximal to the allograft with evidence of thinning of the allograft along its length. Note. The black lines indicate the length of resection, resulting in a 7.5-cm nerve gap. The arrows represent the histological sections. Note an abundance of myelinated axons in the proximal median nerve, with a reduction by the mid-portion of the nerve allograft and no axons within the distal median nerve.

Figure 3.

Patient 4 with intraoperative findings of an extensive area of scarred ulnar nerve at the level of the elbow. Note. The arrows reflect the area of the nerve demonstrated on histology sections below. Note the abundance of myelinated axons in the proximal ulnar nerve just proximal to the allograft. Note the paucity of axons seen both within the allograft and absence in the distal ulnar nerve.

Figure 4.

Schematic of nerve regeneration across a nerve gap. Note. (a) Macrophages accumulate within the scaffold bridging the nerve gap, producing angiogenic factors, including vascular endothelial growth factor (VEGF), resulting in endothelial cell recruitment and vessel formation.^, (b) As blood vessels form, Schwann cells migrate on this vessel network, and in turn, fibroblasts interact with Schwann cells forming cellular cords, similar to Bands of Bungner, for (c) directed axon growth. Reproduced with permission from Pan et al.

Figure 5.

Relationship of motor neuron numbers innervating muscle (x-axis) to muscle function (y-axis). Note. (a) Using the Sunderland and Seddon classifications of nerve injury, severe nerve injuries can reduce motor neurons’ axonal projections to muscle to less than 20% to 30% of original numbers, which are required for adequate muscle function.^, (b) The reconstruction of nerve gaps in rodents using various grafts revealed that allografts, more so than autografts, are sensitive to graft length. Repaired nerve gaps using allografts greater than 4 cm did not facilitate the needed 20% to 30% of axon regeneration across the ANA to downstream muscle to restore function.^, Reproduced with permission from Saheb-Al-Zamani et al. ANA = acellular nerve allograft.