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Page 2 of 10 Berberoglu et al. Plast Aesthet Res 2024;11:14 https://dx.doi.org/10.20517/2347-9264.2023.101

these patients experience complications including severe neuropathic pain and limited participation in
[3]
physical and occupational activities . Unfortunately, this often results in psychological stress and poor
[4]
quality of life . Prosthesis use allows patients to restore independence and reintegrate into social and
occupational activities. Myoelectric prostheses demonstrate advanced capabilities compared with body-
powered prosthetic limbs, such as precise hand, wrist, and finger movements and greater degrees of
freedom . However, patients abandon these prosthetic devices at varying rates (0%-75%), due to the lack of
[5]
comfort of the socket, neuroma pain, and the lack of realistic sensory feedback . Current prosthetic
[6,7]
technologies mostly acquire discrete control signals from the limited number of available sites through
surface electrodes, which limits signal fidelity, reliability, and multifunctionality . In addition, the lack of
[8]
meaningful sensory and proprioceptive feedback, the necessity for frequent recalibration, and the amount of
training result in dissatisfaction with these devices . Thus, despite the immense developments in
[8,9]
prosthetics technology, there is still a need for an interface that can provide a natural experience with
optimal activity and control. Allowing a patient to intuitively control more than a single movement at a
time is ideal, but this requires separate and independent motor and sensory signals captured from the
residual peripheral nerves .
[8]
Rehabilitation for individuals with amputations is often limited by postamputation pain, including
symptomatic neuromas and phantom limb pain (PLP) . This often results in debilitating chronic
[10]
neuropathic pain that significantly limits prosthetic use and interferes with activities of daily living
(ADLs) [11,12] . Current therapeutic interventions are often inadequate, as there is no identified clinical “gold
standard” for the surgical treatment of neuromas [13,14] . Therefore, there is a need to develop a robust and
reliable technique to address postamputation pain.

The Regenerative Peripheral Nerve Interface (RPNI) has been developed to overcome these problems. The
RPNI is a simple and safe technique that serves as a stable, biological nerve interface [15-18] . By leveraging the
physiologic processes of nerve regeneration, muscle regeneration, and reinnervation, RPNIs have a dual
purpose of providing enhanced motor control of prosthetic devices and reducing postamputation pain . It
[18]
can be performed after neuroma excision or prophylactically at the time of amputation . Building from
[19]
experience with the initial RPNI construct, the Dermal Sensory Regenerative Peripheral Nerve Interface
(DS-RPNI), Composite Regenerative Peripheral Nerve Interface (C-RPNI), and the Muscle Cuff
Regenerative Peripheral Nerve Interface (MC-RPNI) have also been designed. This article reviews current
concepts of RPNIs and focuses on the multiple applications of its novel modifications to enhance the
functionality of myoelectric prostheses and exoskeleton devices.

REGENERATIVE PERIPHERAL NERVE INTERFACE (RPNI)
The RPNI is a biological interface composed of a transected peripheral nerve implanted into an autologous
free skeletal muscle graft [15,16,18] . Initially, all transected peripheral nerves in the residual limb are identified,
[18]
isolated, and dissected from the surrounding soft tissues . Dissection of large proximal nerves, such as the
sciatic nerve, into three or four fascicles is recommended to improve axon-to-muscle fiber ratio [18,20] . For
each of the isolated nerves, healthy muscle grafts are harvested parallel to the muscle fibers either directly
from the amputated limb or at a distal site with a separate incision [18,20] . The most commonly used graft size
to optimize revascularization is 30 to 40 mm long, 15 to 20 mm wide, and 5 to 6 mm thick [18,20] . Finally,
transected peripheral nerves are implanted into the center of the muscle graft [Figure 1]. RPNIs should be
created in a proximal area, remote from the surgical incision site and weight-bearing surfaces of the residual
limb. The time required to implant a single RPNI construct is 7 to 10 min .
[20]