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Page 2 of 15 Gunderson et al. Plast Aesthet Res 2023;10:50 https://dx.doi.org/10.20517/2347-9264.2023.42

(± 2.00) and 5.05 mm (± 1.06), respectively. Pelvic limb nerves consisted of two dorsal and one ventral nerve with
an average circumference of 6.27 mm (± 1.79) and 5.40 mm (± 0.53), respectively.

Conclusions: These anatomic data inform the surgical approach and manufacture of a sensory ONI for chronic
testing in awake, freely ambulating animals for future clinical translation.

Keywords: Amputation, prosthesis, prostheses, neural interface, clinical translation, large animal, osseointegration,
neuroprosthesis

INTRODUCTION
The use of large animals as preclinical models is a key step in the translation of biomedical research towards
their ultimate application in human patients. Robust, long-term simulation in large animal models is
essential to adequately assess the safety and function of any device or intervention prior to human testing.
There have been recent technological advances in methods of neural interfacing, such as the
Osseointegrated Neural Interface (ONI), which have profound implications for the human amputee
population. These interfaces, in combination with advanced prostheses, hold the promise of bi-directional
communication in the form of intuitive motor control and sensory feedback between an amputee and their
prosthesis; the validity of these new technologies to provide chronic and stable communication between
native nerves and advanced prosthetics is required . Dingle et al. have demonstrated the durability of ONI
[1-3]
in a rabbit model, but furthering this objective requires longitudinal studies in a clinically translatable large
animal model .
[3-4]

Analysis of currently available animal models in neural prosthetic interfacing was recently performed by
Aman et al. This article identified that many pilot studies utilize the rat model and rabbit model. Many
limitations to these smaller animal models were discussed, including biological differences between rats and
humans as well as high infection and self-mutilation rates in rabbit models. Most importantly, though, more
comparable anatomy is required to test human-sized devices in a model over time to prove their safety,
longevity, and efficacy, which is not possible in small animal models. This article identified a relative dearth
of large animal models for the chronic evaluation of peripheral neural interfacing, with no published large
animal models for the evaluation of Osseointegrated Neural Interfacing .
[5]

One ungulate model has been published. Clites et al. demonstrated the utility of a caprine (goat) transtibial
and transfemoral hindlimb amputation model for the evaluation of agonist-antagonist myoneural
interfacing for prosthetic control. This study demonstrated the chronic stability and safety of an
osseointegrated prosthetic device up to day 190 in transfemoral amputation, showing promise for this
model in the field of ONI . Similarly, ovine (sheep) models are well established for osseointegrated
[6]
prosthetics (OI) research [7-10] . Adult sheep share a similar size, weight, and bone structure to adult humans,
and thus are an accepted large-animal model for bone and implant biomechanics . The standard ovine
[11]
model for osseointegration consists of a metacarpal amputation of the thoracic limb as an analogy for
transtibial amputation in humans. The ovine model has become the gold standard for long-term large
animal OI evaluation, with studies showing stability of at least two years . It follows, then, that the gold
[7]
standard for ONI using OI prostheses should be this same clinically robust model: the sheep.

Existing OI ovine models do not consider the implications for neural control of the advanced prosthesis.
While there are generalized topographical maps of the nerves of the thoracic and pelvic limbs of sheep,
more granular information, particularly distal to the carpal and tarsal joints where the amputation is
performed, is lacking. The data are crucial for creating a suitable osseointegrated prosthesis with sensory