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axons regenerating into the graft and reinnervating the CURRENT SURGICAL STRATEGIES FOR
transplanted muscle and skin, so as to establish motor NERVE REPAIR AND REGENERATION
[1]
control and receive sensory input. Nerve damage
is inevitable in the process of transplantation, from Surgical coaptation (tension‑free repair)
peripheral axonal degeneration occurring from the Because additional nerve length can usually be
time of organ harvest to surgical reconnection of the harvested from the donor, tension‑free direct
donor tissue to the host. Host cortical reorganization end‑to‑end neurrorraphy of recipient and donor nerve
plays a paramountrole in the restoration of function, as stumps can typically be achieved. Nerve coaptations
the lack of sensory input from the injured or missing have been and are still widely used for various
body region results in aberrant cortical response to procedures in reconstruction, peripheral nerve injury
restoration of sensory input from, and motor output to, repair, and in VCA. Opening of the donor nerve
the newly innervated tissue following prolonged periods perineurium and induction of deliberate nerve injury
[3]
of denervation. Peripheral nerve regeneration is a slow during end‑to‑side coaptation has been shown to
process, occurring at 1‑3 mm/day, partly depending on increase the regeneration of axons from the host into
the microenvironment surrounding axonal sprouts and the donor axons. In the context of facial transplants,
[7]
caliber of the nerve. [4] tension‑free nerve coaptations have been shown to
Thus, there exists a need for more effective and consistent have the most predictable and reliable results in
[8]
strategies for nerve regeneration in VCA. This area is nerve reconstruction. Performing the neurotomy in
a popular field of study in the context of peripheral the epineurial vs. perineurial layer has not yielded a
neuropathy repair, but the VCA context provides unique definitive determination of which procedure yields the
challenges in the necessity for immunosuppression best postoperative functional results. [9]
and the circumstances in which the transplantation is Nerve transfers are another method by which healthy
performed. axons that traditionally serve one area can be rerouted
and coapted to provide sensory and motor function
PATHOPHYSIOLOGY OF NERVE to another. However, the clinical applicability of this
DAMAGE AND REGENERATION procedure is untested in VCAs, in the context of the
cortical somatosensory reorganization of these redirected
Following transplantation, axons within the graft undergo sensory and motor domains. [10]
Wallerian degeneration. Originally thought to be mediated Nerve autograft
by impaired transport of nutrients to distal axonal Nerve autografting is a surgical procedure that allows
segments and subsequent death, Wallerian degeneration for repair of relatively long lesion gaps with the patient’s
is now considered a product of a self‑destruct program own tissues when nerve coaptation cannot be performed
distinct from that of apoptosis. [5]
without excess tension on the nerve stumps. Although
Although Wallerian degeneration ultimately claims axons the graft can provide the scaffold for regrowth with
distal to the site of organ harvest, the reorganization of Schwann cells and neurotrophic factors, there is obvious
Schwann cells and macrophages around the dying axons secondary morbidity associated with graft harvest. Nerve
fosters an environment that favors axonal regeneration. autografting has primarily been used in a variety of
However, in the context of VCA, this process is affected clinical scenarios requiring nerve repair. Since allografts
[11]
by the presence of widespread axonal damage and by from donor nerve tissue can be supplemented to the
the need for a balance between immunosuppression and existing composite transplantation without any additional
tissue rejection. immunosuppressive burden, nerve autografts have limited
use in the context of VCA. In addition, challenges in
Due to the transplantation process, all cellular nerve large‑caliber nerve revascularization and limited capacity
components distal to the transection point are derived for diffusion‑mediated perfusion of such nerves must be
from donor populations. Regeneration of host peripheral taken into consideration. [12]
nerves requires host‑derived Schwann cells to populate
the distal stump, which in turn requires proliferative and Nerve allograft
migration signals. Induction of these signals seems to While autografts are considered ideal in the case of
require partial rejection of the VCA to eliminate donor peripheral nerve damage since these grafts do not face
Schwann cells. Thus, immunosuppression regimens any immunological mismatch, such is not the case in
should be carefully determined to provide optimal nerve allografts. However, the primary benefit of this
nerve regeneration through optimal host Schwann latter method is that the secondary morbidity associated
cell proliferation and migration while avoiding greater with autograft harvesting, such as sensory loss and
tissue injury during the controlled rejection process. scarring, is avoided. When performed in the context
[13]
The complete lack of a rejection period may potentially of VCA, where immunosuppression is already used to
block host Schwann cell migration, leading to impaired avoid rejection of the primary tissue, use of additional
peripheral nerve growth. If rejection leads to rapid donor nerve allografts from the cadaveric source of the VCA
Schwann cell death, unsupported endoneurium may tissue to ensure tension‑free nerve coaptation does not
degenerate, blocking further regeneration. [6] add new immunological consequences. Furthermore,

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