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Berberoglu et al. Plast Aesthet Res 2024;11:14 https://dx.doi.org/10.20517/2347-9264.2023.101 Page 5 of 10

Figure 2. The Dermal Sensory Regenerative Peripheral Nerve Interface (DS-RPNI) construct. (A) Illustrative schematic consisting of
deepithelialized skin graft secured around the sensory nerve; (B) DS-RPNI in vivo in a rat at the time of fabrication.

feedback from various anatomical locations and evoke specific sensations by selective activation of different
sensory fibers .
[9]

In addition to its potential role of restoring natural sensation in individuals with amputations, DS-RPNI is
used in the management of chronic neuropathic pain localized to a specific sensory nerve as an alternative
treatment strategy to traditional neurectomy. Hart and Brown reported two cases, one ankle injury and the
other mastectomy, to highlight the results of DS-RPNI surgery in patients with chronic pain and positive
Tinel’s sign . Visual analog scale pain scores significantly decreased from 9-10 to 1-3, postoperatively .
[28]
[28]
COMPOSITE REGENERATIVE PERIPHERAL NERVE INTERFACE (C-RPNI)
An ideal prosthetic neural interface would be capable of achieving bidirectional motor control and sensory
feedback . Thus, RPNI and DS-RPNI were combined to create the novel construct, the Composite
[29]
Regenerative Peripheral Nerve Interface (C-RPNI). Utilization of both components of this interface
simultaneously has the potential to pave the way for the realization of the ideal prosthetic device control
strategy.

The C-RPNI is composed of a mixed sensorimotor nerve that is implanted into a construct of a free muscle
graft secured to a dermal graft . The central tendinous tissues and a small segment of epimysium are
[30]
removed from the muscle graft. Following the preparation of dermal and muscle grafts and isolation of the
transected nerve, the epineurium of the transected nerve end is secured to the area of the muscle graft where
the epimysium was removed. Next, the dermal graft is positioned on the muscle graft where it fully covers
the nerve and majority of the muscle. Then, proximal and distal parts of the construct are attached to the
[30]
femur periosteum to secure the construct in its place [Figure 3] .

Peripheral nerves show a preference for the type of end organ they reinnervate . Regenerating motor
[30]
neurons have a tendency to reinnervate motor pathways, while sensory neurons preferentially innervate
cutaneous branches of the nerve [30,31] . The C-RPNI relies on the inherent preferential reinnervation principle
of the target nerve itself to facilitate reinnervation. Motor fibers innervate the muscle graft, while the
[30]
sensory fibers innervate the dermal component of the C-RPNI . In more distal extremity amputations,
individual RPNI and DS-RPNI constructs are implanted, since motor and sensory fascicles can be surgically
separated. However, at proximal levels, bundles of motor and sensory axons travel together. Thus, surgical
separation of the intermingled axons is often difficult and does not allow for separate RPNI and DS-RPNI
constructions. Therefore, the C-RPNI would be the preferred RPNI strategy in treating patients who present
[30]
with proximal, transhumeral amputations .