Experimental Testing of Bionic Peripheral Nerve and Muscle Interfaces: Animal Model Considerations

Abstract

Introduction: Man-machine interfacing remains the main challenge for accurate and reliable control of bionic prostheses. Implantable electrodes in nerves and muscles may overcome some of the limitations by significantly increasing the interface's reliability and bandwidth. Before human application, experimental preclinical testing is essential to assess chronic in-vivo biocompatibility and functionality. Here, we analyze available animal models, their costs and ethical challenges in special regards to simulating a potentially life-long application in a short period of time and in non-biped animals. Methods:We performed a literature analysis following the PRISMA guidelines including all animal models used to record neural or muscular activity via implantable electrodes, evaluating animal models, group size, duration, origin of publication as well as type of interface. Furthermore, behavioral, ethical, and economic considerations of these models were analyzed. Additionally, we discuss experience and surgical approaches with rat, sheep, and primate models and an approach for international standardized testing. Results:Overall, 343 studies matched the search terms, dominantly originating from the US (55%) and Europe (34%), using mainly small animal models (rat: 40%). Electrode placement was dominantly neural (77%) compared to muscular (23%). Large animal models had a mean duration of 135 ± 87.2 days, with a mean of 5.3 ± 3.4 animals per trial. Small animal models had a mean duration of 85 ± 11.2 days, with a mean of 12.4 ± 1.7 animals.Discussion: Only 37% animal models were by definition chronic tests (>3 months) and thus potentially provide information on long-term performance. Costs for large animals were up to 45 times higher than small animals. However, costs are relatively small compared to complication costs in human long-term applications. Overall, we believe a combination of small animals for preliminary primary electrode testing and large animals to investigate long-term biocompatibility, impedance, and tissue regeneration parameters provides sufficient data to ensure long-term human applications.

Dielectric Elastomer Actuators, Neuromuscular Interfaces, and Foreign Body Response in Artificial Neuromuscular Prostheses: A Review of the Literature for an In Vivo Application

“…[30,31,[37][38][39] There are no data in using electroneuronography (ENG) instead of EMG in external prosthesis control; for completely substituting a muscle, ENG could be more useful if the natural muscle must be surgically excised making impossible to have an EMG signal; in this case, ENG sensors should be used. [112,113] As described previously, use of a wireless amplification system to communicate with an external prosthesis (residual muscle activation signal-sensorwireless communication with amplifier-signal amplificationexternal prosthesis controller) can reach a sufficient voltage to actuate the external myoelectric prosthesis. [48][49][50][51] This same approach should be applicable to artificial muscles implants.…”

Tutorial: a guide to techniques for analysing recordings from the peripheral nervous system

“…There are both ethical and scientific reasons for using animal models; however, these models also lead to several associated translational challenges. A recent detailed review of animal models used for peripheral nerve interface development can be found in Aman et al [90].…”

Editorial: Getting Neuroprosthetics Out of the Lab: Improving the Human-Machine Interactions to Restore Sensory-Motor Functions

“…Most of neuroprosthetic development is performed in rodents, often serving as of proof of concept ( Aman et al, 2020 ). Neuroprosthetics with the potential for clinical translation is often tested in larger animals to determine chronic safety and efficacy and ultimately enter human clinical trials.…”