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Berberoglu et al. Plast Aesthet Res 2024;11:14 https://dx.doi.org/10.20517/2347-9264.2023.101 Page 7 of 10

Figure 4. The Muscle Cuff Regenerative Peripheral Nerve Interface (MC-RPNI). (A) Illustrative schematic of the MC-RPNI. The
peripheral nerve in continuity innervating its distal target can be seen in yellow within the surrounding muscle graft; (B) MC-RPNI in
vivo immediately following fabrication in a rat. Muscle tissue (M) and common peroneal nerve (N).

simultaneous control of multiple degrees of freedom can be achieved with the MC-RPNI, as distally
dissected nerves can be implanted into individual muscles without significant signal contamination [32,33] .
Given its biogenic origin and strategic placement, the MC-RPNI avoids detriment to distally innervated
targets, and preclinical rodent studies have demonstrated the lack of downstream muscle compromise [32,33] .
Thus, the MC-RPNI has substantial promise for the widespread utilization of safe, accurate, and reliable
exoskeleton devices in those living with extremity weakness.

DISCUSSION
Innovative approaches to human-prosthetic interfacing are continuously advancing neural interface
technology and enabling the development of next-generation sophisticated prosthetic limbs. In this review,
we provided a detailed description of RPNI technology that takes advantage of the basic muscle and nerve
physiology for real-time control of myoelectric prostheses. One of the other promising current approaches
to provide intuitive control of advanced myoelectric prostheses is Targeted Muscle Reinnervation (TMR).
[39]
TMR is a surgical technique developed in the early 2000s for individuals with amputations . In this
procedure, residual mixed peripheral nerves from the amputated limb are transferred to small intact motor
[39]
nerves . Distinct from RPNI, TMR relies on surgical denervation of functional muscle targets so that the
newly transferred nerve can reinnervate successfully [39,40] . Following reinnervation, neural signals from
transferred nerves cause target muscles to contract, which provides additional EMG signal sites for
prosthetic control. TMR has been performed in more than 100 patients at various amputation levels to
provide improved degrees of prosthetic control . However, barriers remain to getting intuitive control of
[41]
the prosthetic limb and more widespread implementation of these surgical techniques. Skin electrodes used
in TMR to record sEMG signals demonstrate limitations that impede the precise measurement of muscle
contractions [40,42] . Recording electrical activity from the body surface may alter the signal characteristics due
to positional and physiological changes [40,42] . In addition, sEMG recordings are prone to crosstalk and
interference from adjacent muscles (or other electrodes), which necessitates advanced signal processing
systems for the neural interface to be effective . Furthermore, reinnervation of the target muscle by
[43]
multiple large peripheral nerves results in a limited number of EMG recording sites and overlapping signals,
which requires the implementation of complex pattern recognition algorithms to assign the signals to the
intended control targets . Thus, TMR demands more technical and scientific proficiency compared to
[40]
RPNI. In addition to its use as a mechanoneural interface for intuitive prosthetic control, patients may also
experience attenuated residual limb pain (RLP) and PLP following TMR . Mioton et al. showed significant
[41]
reductions in RLP (from 6.4 ± 2.6 to 3.6 ± 2.2) and PLP (from 6.0 ± 3.1 to 3.6 ± 2.9) following TMR
surgery . Dumanian et al. conducted the first randomized clinical trial and assigned patients with chronic
[44]
[45]
pain to TMR or standard care with traditional neurectomy . Although they reported a greater
improvement in PLP and RLP in the TMR cohort, pain score reduction failed to reach statistical
significance .
[45]