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Buncke. Plast Aesthet Res 2022;9:38 https://dx.doi.org/10.20517/2347-9264.2022.08 Page 7 of 17

Table 2. Nerve conduits cleared by the FDA [31,49]
Device name Material FDA clearance date
NervAlign Porcine pericardium 02/10/2022
NeuroShield Chitosan 05/21/2019
Nerbridge Polyglycolic acid and porcine dermis-derived collagen 01/22/2016
Reaxon Chitosan 12/02/2015
NeuraGen 3D Bovine type-1 collagen with inner matrix collagen/chondroitin-6 sulfate 4/24/2014
Neurolac nerve guide Poly (DL-lactide-co-ε-caprolactone) 10/10/2003
Surgisis nerve cuff Porcine small intestine submucosa 05/15/2003
(Axoguard nerve connector)
Collagen nerve cuff Collagen 09/21/2001
NeuroGen nerve guide Collagen 07/22/2001
Salumedica nerve cuff Polyvinyl alcohol hydrogel 11/24/2000
Neurotube Polyglycolic acid 03/22/1999
Fastube nerve regeneration device Unknown 07/10/1985

Nerve allograft
Nerve allografts were sought as an alternative to autografts, as nerve allografts can be prepared and stored in
tissue banks, do not lead to a secondary donor surgical site and provide the proper structural guidance
needed for peripheral nerve regeneration . Engineered nerve allografts were first noted in the literature in
[18]
the 1960s, which were pre-treated by freezing and irradiation [18,27,28] . However, the initial success of
engineered nerve allografts faced limitations during early surgical use, as grafts were noted to show delayed
axonal outgrowth, elicited an immunologic response and resulted in nerve graft rejection [50-53] . Research to
improve nerve allograft outcomes continued, including major histocompatibility complex (MHC)
matching, patient immunosuppression and nerve graft processing methods. In 1985, Mackinnon et al.
attempted MHC matching in rats and found good regeneration in MHC matched allografts and poor
regeneration in the MHC unmatched grafts .
[30]

In 2001, Mackinnon evaluated the clinical use of donor allograft nerve that was blood-type (ABO) matched
to patient recipients . These ABO-matched nerve allografts showed good sensory and motor outcomes in
[34]
[34]
patients . The immunologic response in cellular allogenic nerve grafts was noted to decrease over time as
the donor Schwann cells were replaced by host Schwann cells , but immunosuppressive treatments,
[54]
including Cyclosporin-A and tacrolimus (FK506), were still required . Alternative areas of research, such
[18]
as nerve allograft pre-treatments, were investigated to circumvent the need for immunosuppressives.
Research in engineered nerve allograft pretreatment development has included cryopreservation,
lyophilization , freeze/thaw cycling , cold storage, chemical treatments to extract cellular debris or pre-
[56]
[55]
degenerate the graft [33,35,36,57,58] , and irradiation . The most prolific engineered nerve allograft pre-treatment
[27]
[33]
protocol used in literature was proposed by Sondell et al. in 1998, which used Triton X-100 and sodium
deoxycholate solution to chemically lyse cells . This pre-treatment protocol resulted in the removal of the
[59]
myelin sheath and cells from engineered nerve allografts, resulting in a satisfactory nerve regeneration
response in vivo . Later research was conducted in 2001 by Krekoski et al. showing that chondroitin sulfate
[33]
proteoglycan glycosaminoglycan side chains, known to inhibit axonal growth by functional blockade of
laminin, could be removed from the nerve by treatment with a chondroitinase ABC enzyme . The
[35]
methods proposed by Krekoski et al. showed that chondroitinase pre-treated engineered nerve allografts
improved the growth-promoting properties of the nerve allografts and resulted in more axons growing at
longer lengths through the chondroitinase treated allografts compared to grafts that were not treated with
[35]
chondroitinase . Several years later, in 2004, Hudson et al. proposed an engineered nerve allograft pre-