Intraneural fibrosis and loss of microvascular architecture-Key findings investigating failed human nerve allografts

Background: Processed nerve allografts are increasingly used in clinical nerve reconstruction with promising results. However, allograft failure has been reported, leading to chronic pain and persistent loss of function. In the present work, we performed a histological and immunohistochemical analysis of two failed allograft reconstructions of a sensory human nerve one year after primary surgery. Methods: Two patients with a superficial radial nerve injury underwent nerve reconstruction with processed nerve allografts. The clinical follow-up was complicated by severe neuropathic pain and absent sensory reinnervation. Consequently, the failed allografts were excised with subsequent histological and immunohistochemical examinations. For that purpose, the collagen content and neurofilament network as well as the blood and lymphatic vasculature were analysed in the center of the specimens. Results: Histology revealed increased fibrosis, fatty degeneration, and disorganised proliferation of nerve fibres. Moreover, the microvascular network within the allografts was characterised by increased numbers of microvessels, whereas no difference was found concerning the lymphatic vasculature. Conclusion: The herein presented histological and immunohistochemical findings indicate that the failure of human allografts is associated with loss of the physiological microvascular architecture. Future studies elucidating the complex interplay of angiogenesis, lymphangiogenesis and axonal regeneration are required to better understand the mechanisms of human allograft failure. (c) 2021 The Authors. Published by Elsevier GmbH. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

Automated summary

Histological and immunohistochemical analysis of two failed allograft reconstructions indicate that the failure of human allografts may be associated with the loss of physiological microvascular architecture. Further studies are needed to elucidate the complex interplay of angiogenesis, lymphangiogenesis, and axonal regeneration in understanding the mechanisms of human allograft failure.