Failed Acellular Nerve Allografts: A Critical Review

Area of Science:

• Regenerative Medicine
• Neurosurgery
• Biomaterials Science

Background:

• Acellular nerve allografts (ANA) are increasingly used for peripheral nerve reconstruction.
• While effective, some ANA grafts fail to promote axonal regrowth, with unclear underlying reasons.
• This study investigates clinical and histological findings in failed ANA cases within a specialized department.

Purpose of the Study:

• To examine the outcomes of acellular nerve allograft (ANA) procedures in a specialized peripheral nerve surgery department.
• To identify and discuss potential mechanisms of failure in ANA grafts.
• To correlate clinical observations with histological findings in failed cases.

Main Methods:

• Identification of failed ANA grafts using Medical Research Council Classification (MRCC) thresholds (S3, M3) and lack of symptom improvement or need for revision surgery.
• Inclusion of cases indicated for nerve pain/dysesthesia without subjective improvement.
• Literature review and detailed histological analysis of two failed cases.

Main Results:

• Eight failed ANA procedures were identified from 99 allograft records (74 patients), involving various nerve types and lengths.
• Histological findings in two cases showed vascularization without axonal regeneration, reduced large myelinated fibers in chronic injuries, and a preference for small fiber regeneration.
• One postoperative infection was noted among the failed cases.

Conclusions:

• The reasons for acellular nerve allograft (ANA) failure in diverse clinical contexts remain unclear.
• Graft failure is likely multifactorial, involving patient, graft, and surgical technique contributions.
• Further clinical and histological investigations of ANA failures are crucial for understanding failure mechanisms.