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Page 8 of 17 Buncke. Plast Aesthet Res 2022;9:38 https://dx.doi.org/10.20517/2347-9264.2022.08

treatment protocol using Sulfobetaine-16, Triton X-200, and Sulfobetaine-10 to improve cell lysis while
[36]
maintaining the extracellular matrix . The Hudson et al. study showed that engineered nerve allograft pre-
treatment with mild detergents resulted in axon densities that were comparable to nerve isografts
[36]
(considered to be the equivalent of nerve autografts in pre-clinical studies) . Furthermore, these Hudson
pre-treated engineered nerve allografts also showed 910% more axon density than thermally treated
engineered neve allografts and 401% more axon density than the pre-treatment process proposed by
Sondell . Pre-treating engineered nerve allografts with both the Hudson pre-treatment and the Krekoski
[33]
pre-treatment has been found to be the most effective pre-treatment for engineered nerve allografts, when
compared among other well-established nerve allograft pre-treatment protocols . Avance nerve graft was
®
[59]
[35]
[37]
developed using both pre-treatment methods outlined by Hudson et al. and Krekoski et al. .
[36]
The effort to develop an engineered nerve allograft utilizing these two protocols involved over 20 years of
research by two research groups, and came to fruition in 2007 when Avance nerve graft was made available
as an off-the-shelf engineered nerve allograft for clinical use . To date, Avance nerve graft is the only
[37]
engineered nerve allograft commercially available in the United States for clinical use. The initial pre-
clinical studies showed that Avance nerve allografts did not show an immunogenic reaction and maintained
the native extracellular matrix structure of the nerve, including laminin, a protein critical to neurite
[60]
outgrowth .

CLINICAL USE OF AVANCE NERVE GRAFT
The first clinical report of Avance nerve graft use was published in 2009 and involved 8 patients with 10
sensory nerve repairs [Table 3]. The average gap length was 2.23 cm (range 0.5-3 cm), and all patients had
[61]
[61]
sensory improvement by 9 months . Through 2016, several clinical publications demonstrated that
adequate sensation was achieved in sensory nerve gap repair using Avance nerve graft in gaps up to 30 mm
in the upper and lower extremity, providing an alternative to autografts [64,65,76-79] . Engineered nerve allografts,
such as Avance nerve graft, provided advantages over nerve autografts, including circumventing donor-site
morbidity, off-the-shelf availability, easy to use, and reduced operative time [61,64,65,76-78] . Further research
expanded the gap length and nerve type repaired with Avance nerve graft.

In 2012, Brooks et al. published the first results of nerve gaps repaired with Avance nerve graft up to 50 mm
in length, which included 76 nerve gaps averaging 22 mm (range, 5-50 mm) in sensory, mixed, and motor
nerves located in the upper and lower extremity . Brooks and colleagues showed meaningful recovery in
[62]
87.3% of nerve gaps repaired with Avance nerve graft, where meaningful recovery was defined as a return of
motor recovery to M3 or greater and sensory recovery to S3 or greater using the Medical Research Council
Classification (MRCC) scale . Additionally, there were no significant differences in sensory and motor
[62]
[62]
outcomes between sensory, mixed, or motor nerve repairs . In late 2012, Cho et al. published on 51
sensory, mixed, and motor nerve gaps repaired with Avance nerve graft in the upper extremity only . Cho
[63]
et al. and colleagues showed in nerve gaps averaging 23 mm (range, 5-50 mm), 86% of repairs achieved S3
or M4 and above recovery . The adoption of engineered nerve allograft into clinical use and early
[63]
publications led to the development of an evidence-based algorithm.

In 2012, Ducic et al. discussed that direct repair should be used in nerve gaps less than 5 mm, nerve
conduits should be used in gaps 5 mm to 15 mm, engineered nerve allografts should be used in nerve gaps 5
[47]
mm to 50 mm, and nerve autografts should be used in nerve gaps 5 mm to greater than 50 mm . This
suggested that both engineered nerve allograft and nerve autograft could be used in similar gap sizes. By
2014, it was proposed by Rinker et al. that engineered nerve allografts, such as Avance nerve graft, were the
most significant development in peripheral nerve surgery since the introduction of microsurgery .
[80]