Page 19 - Read Online

Page 12 of 17 Buncke. Plast Aesthet Res 2022;9:38 https://dx.doi.org/10.20517/2347-9264.2022.08

[43]
chronic sensory deficits . The acute and chronic comorbidities related to nerve autograft harvest should be
a consideration for the surgical algorithm of surgeons performing peripheral nerve repair. Furthermore,
alternatives to nerve autografts should be considered by evaluating evidence-based outcomes. The advent of
engineered nerve allografts has provided one such alternative to nerve autografts that circumvent the
associated donor-site morbidities associated with nerve autografts and offer promising outcomes.

The development of engineered nerve allografts has required decades of research, but has been proven to
achieve successful clinical outcomes. The early use of pre-treated engineered nerve allografts showed limited
[85]
successful outcomes [50-53] or required immunosuppression . With later advancements in the field, the
advent of an optimized nerve allograft pre-treatment method allowed for the successful implantation of
engineered nerve allografts without the use of immunosuppressives and with outcomes that are comparable
to autograft [62,63] . The development and clinical use of this off-the-shelf engineered nerve allograft, Avance
nerve graft, has finally driven changes in the peripheral nerve repair surgical algorithm. Initial clinical
research supported the use of engineered nerve allografts in nerve gaps up to 30 mm, with a later expansion
of successful clinical use for nerve gap repair up to 50 mm. However, a recent clinical study supports the use
of engineered nerve allografts for both sensory and mixed/motor nerve repair in gaps up to 70 mm in
length . With this recent publication, the application of engineered nerve allografts can be confidently
[74]
used clinically in nerve gaps up to 70 mm in length.

The successful outcomes of peripheral nerve repair with engineered nerve allograft are promising; however,
limitations exist in the literature, including the lack of randomized controlled clinical trials comparing
engineered nerve allograft to autograft. While retrospective clinical trials lack stringent controls seen in
randomized clinical trials, the retrospective studies reviewed in this manuscript provide the best
comparative data available to date in the repair of peripheral nerve gaps. By evaluating the clinical data
chronologically, it is clear that technological advancements in peripheral nerve repair support the use of
engineered nerve grafts with increasing gap lengths over time. This method of chronological presentation
serves to present the data as it has been shared with the field, ensuring a balanced presentation of
meaningful studies to the clinical community. It is expected that technology will continue to improve, thus
changing the future surgical algorithm for peripheral nerve repair.

The clinical application of materials and techniques currently in early-phase research will continue to
change the landscape of peripheral nerve repair. Some notable early-phase research includes engineered
nerve allografts, engineered nerve conduits with and without fillers, and cellular and non-cellular graft
additives. Engineered nerve allografts have included various processing techniques, including cold
preservation , freeze thawing , detergents , and irradiation . While various engineered nerve allografts
[87]
[86]
[51]
[36]
have been researched, only Avance has been made available commercially as an off-the-shelf engineered
nerve allograft. This limits the ability to evaluate the clinical efficacy of different engineered nerve allografts.
Engineered nerve conduits have been investigated using various synthetic and natural materials, which may
be either resorbable or non-resorbable.
A recent meta-analysis found that autograft vein conduits, autograft muscle-vein conduits, engineered
collagen tubes (e.g., NeuroMatrix, Neuroflex, NeuraGen® nerve guide), and Neurolac™ (a bioresorbable
synthetic material) were the most studied and best nerve conduit options . New materials for conduit
[88]
fillers and additives have been explored to enhance conduit efficacy and increase the application length of
these materials. Research on new conduit filler materials includes fibrin, laminin, collagen, and synthetic
aligned matrices . Furthermore, additives have been investigated with various nerve graft materials,
[89]
including cellular (e.g., Schwann cells, fibroblasts, and bone stromal cells) and non-cellular (e.g.,