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Toyoda et al. Plast Aesthet Res 2022;9:17 https://dx.doi.org/10.20517/2347-9264.2021.118 Page 11 of 17

[65]
primary TMR had significantly less frequent and less intense neuroma symptoms . Another multi-
institutional cohort study of major limb amputees (due to any reason) compared 51 patients who had
[66]
[66]
primary TMR to 438 amputees who did not have TMR . Evaluation by Valerio et al. at a median follow-
up of 330 days demonstrated that those with primary TMR had significantly less residual limb and phantom
limb pain than the control group. These results were corroborated by a recent cohort study of primary TMR
patients. In a single surgeon, single-institution study, vasculopathic patients undergoing BKA were treated
with primary TMR or traction neurectomy with muscle implantation . One hundred primary TMR
[67]
patients underwent TMR of the superficial peroneal nerve and tibial nerve and traction neurectomy with
muscle implantation of the remaining major nerves. They were compared to one hundred patients who
underwent only traction neurectomy and muscle implantation of all nerves. Baseline patient characteristics
were similar, and at nearly 10-month follow-up of the primary TMR group and 18.5-month follow-up for
the traction neurectomy group, pain, as defined by residual limb pain and phantom limb pain as well as
represented by opioid use, was significantly better in the primary TMR group. In addition, ambulatory rates
were significantly higher in the primary TMR group . These results have supported multidisciplinary
[67]
collaboration between plastic surgeons and surgical groups such as orthopedists and vascular surgeons who
perform primary amputations at the time of the index operation. Ideally, this would reduce the need for
subsequent operations and reduce total operative time and costs. At the authors’ institution, this
multidisciplinary discussion has resulted in routine consult of the plastic surgeon to perform reconstructive
lower extremity amputations in collaboration with the vascular or orthopedic teams, if not as the primary
surgeon.

REGENERATIVE PERIPHERAL NERVE INTERFACE
History of RPNI
RPNI, similar to TMR, was also originally conceived as a biological interface to harness residual peripheral
nerve signal to control neuroprosthetic devices, but was found incidentally to help with symptomatic
neuroma pain treatment . The RPNI construct consists of a residual peripheral nerve implanted into a
[68]
free, autologous muscle graft after excision of the terminal neuroma bulb. The regenerating axons on the
proximal nerve ending form new neuromuscular junctions on the denervated muscle graft . Kung et al.
[69]
[68]
demonstrated this with both histology and EMG studies on a rat model in which the extensor digitorum
longus (EDL) muscle was removed and used as free muscle grafts. These muscle transfers were later found
[69]
to be successfully revascularized as well as reinnervated . In another study, some rats underwent sham
surgeries of exposure of the soleus muscle while others underwent division of the peroneal nerve and RPNI
[70]
with or without neurotization . At three months, the neurotized RPNI approached sham subjects in
[70]
muscle action potential amplitude and area as well as motor unit numbers . Another rat EDL model study
[71]
by Frost et al. demonstrated that EMG signals could be acquired from RPNIs and translated into real-
time, proportional control of neuroprosthetic hands with reduced signal contamination compared to
control groups. Implantation of microscale electrodes either within the nerves themselves or within the
[72]
[73]
RPNI muscle grafts were both biocompatible with minimal signal noise in rat hind limb models. In these
ways, RPNI bridges the signaling gap between a living peripheral nerve and a mechanical device and
[47]
facilitates motor function and sensory feedback in prosthetic limbs .
Surgical technique of RPNI
Symptomatic neuromas are diagnosed in the usual fashion with history and exams. Intraoperatively, the
neuroma is identified and excised. Larger caliber nerves such as the sciatic nerve may require intraneural
dissection to isolate individual fascicles. Autologous muscle grafts are harvested from the amputated limb or
nearby donor muscles. Grafts are harvested from healthy muscle in the direction of the fibers. Ideally, these
grafts are 5-6 mm thick, and they should be without any atrophy, scar, tendons, or signs of infection. The
proximal end of the transected nerve is placed parallel to the muscle fibers and secured typically with 6-0