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efficacy over other methods.

REGENERATIVE PERIPHERAL NERVE INTERFACES
Similar to TMR, the regenerative peripheral nerve interface (RPNI) was designed as a methodology that
could augment and terminate a nerve’s search for reinnervation by providing an alternative target for the
[25]
newly transected nerve . RPNI was originally developed as a bridge for amputated limbs to be able to
communicate with neuro-prosthetic devices, but quickly evolved into a technique to treat symptomatic
[26]
neuromas . This surgical approach introduces an autologous denervated target in the form of a skeletal
muscle graft, which has a high propensity for reinnervation in order to guide the newly transected nerve
into growing and establishing a connection with this target. For prosthetic control, an implantable electrode
is placed within the reinnervated muscle graft which serves as a signal amplifier in order to communicate
with an external prosthetic device. Similar to the TMR approach, the motor neurons of the transected nerve
[2]
grow into and reinnervate the skeletal muscle graft, switching from growth mode back into transmission .
By providing a target for the transected nerve to reinnervate, RPNI provides the regenerating nerve
somewhere to go and something to do, and harnesses the physiology of a regenerating nerve to prevent the
pathologic formation of a future neuroma [Figure 5].

The first stage of RPNI surgery is the same as a simple neuroma excision, with isolation of the neuroma and
proximal transection of the involved nerve to resect the neuroma. Then, the newly transected nerve is
dissected away from its surrounding tissue, and the proximal transection site is made to be a sharp cut with
[27]
all of the nerve’s fascicles exposed . Once the neuroma is excised and the freshly cut nerve-end is isolated,
the nerve is implanted into a free skeletal muscle graft . If the RPNI is done during an amputation
[2]
procedure, the skeletal muscle graft is harvested from the distal amputated limb to preserve healthy tissue. If
the RPNI is done after the amputation procedure, the skeletal muscle graft is most commonly obtained
from a neighboring skeletal muscle (e.g., the vastus lateralis muscle in the case of lower extremity
amputation). Small grafts carefully harvested from the muscle result in an insignificant alteration to the
muscle’s function . Regardless of the harvest site, it is important to note that these skeletal muscle grafts are
[2]
severed from their blood supply and innervation, while the skeletal muscle in the TMR approach maintains
its blood supply. The grafts are harvested as small cubes that are cut parallel to the axis of the muscle fibers
to ensure a maximal number of intact fibers that retain the capacity to be reinnervated . The skeletal
[27]
muscle grafts are created as cubes, typically 30-40 mm long, 15-20 mm wide, and 5-6 mm thick . Larger
[28]
nerves such as a sciatic nerve may need a large number of muscle fibers to provide an adequate number of
reinnervation targets. In these cases, it is appropriate to dissect the large nerve into multiple fascicular
branches and use multiple muscle grafts for RPNIs .
[27]

The second stage of the RPNI surgery is focused on attaching the harvested skeletal muscle graft onto the
newly transected nerve. The skeletal muscle graft is brought to the transected nerve and placed so that the
[27]
nerve is in the center of the graft and parallel to its muscle fibers . The epineurium of the nerve is then
sutured into the graft using 2 6-0 non-absorbable monofilament sutures before the edges of the muscle graft
are then gently wrapped circumferentially around the nerve to encompass the transected end and secured
[27]
using the same monofilament sutures . This nerve-graft bundle is then buried deep into a bluntly dissected
muscle belly that is away from any weight-bearing surface and surgical incision site before closing the
surgical site [Figure 6] .
[27]

Multiple animal studies have shown evidence of angiogenesis and revascularization of the muscle graft, as
well as the formation of new neuromuscular junctions between the transected nerve and muscle fibers [29,30] .
Moreover, compared to simple neuroma excision, these animal studies have shown that there is an absence