Experimental testing of bionic peripheral nerve and muscle interfaces: animal model considerations

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

Decoding motor neuron activity from epimysial thin-film electrode recordings following targeted muscle reinnervation

Objective. Surface electromyography (EMG) is currently used as a control signal for active prostheses in amputees who underwent targeted muscle reinnervation (TMR) surgery. Recent research has shown that it is possible to access the spiking activity of spinal motor neurons from multi-channel surface EMG. In this study, we propose the use of multi-channel epimysial EMG electrodes as an interface for decoding motor neurons activity following TMR. Approach. We tested multi-channel epimysial electrodes (48 detection sites) built with thin-film technology in an animal model of TMR. Eight animals were tested 12 weeks after reinnervation of the biceps brachii lateral head by the ulnar nerve. We identified the position of the innervation zone and the muscle fiber conduction velocity of motor units decoded from the multi-channel epimysial recordings. Moreover, we characterized the pick-up volume by the distribution of the motor unit action potential amplitude over the epimysium surface. Main results. The electrodes provided high quality signals with average signal-to-noise ratio  >30 dB across 95 identified motor units. The motor unit action potential amplitude decreased with increasing distance of the electrode from the muscle fibers (P 0.001). The decrease was more pronounced for bipolar compared to monopolar derivations. The average muscle fiber conduction velocity was 2.46  ±  0.83 m s−1. Most of the neuromuscular junctions were close to the region where the nerve was neurotized, as observed from the EMG recordings and imaging data. Significance. These results show that epimysial electrodes can be used for selective recordings of motor unit activities with a pick-up volume that included the entire muscle in the rat hindlimb. Epimysial electrodes can thus be used for detecting motor unit activity in muscles with specific fascicular territories associated to different functions following TMR surgery

Proof of concept for multiple nerve transfers to a single target muscle

Surgical nerve transfers are used to efficiently treat peripheral nerve injuries, neuromas, phantom limb pain, or improve bionic prosthetic control. Commonly, one donor nerve is transferred to one target muscle. However, the transfer of multiple nerves onto a single target muscle may increase the number of muscle signals for myoelectric prosthetic control and facilitate the treatment of multiple neuromas. Currently, no experimental models are available. This study describes a novel experimental model to investigate the neurophysiological effects of peripheral double nerve transfers to a common target muscle. In 62 male Sprague-Dawley rats, the ulnar nerve of the antebrachium alone (n=30) or together with the anterior interosseus nerve (n=32) was transferred to reinnervate the long head of the biceps brachii. Before neurotization, the motor branch to the biceps’ long head was transected at the motor entry point. Twelve weeks after surgery, muscle response to neurotomy, behavioral testing, retrograde labeling, and structural analyses were performed to assess reinnervation. These analyses indicated that all nerves successfully reinnervated the target muscle. No aberrant reinnervation was observed by the originally innervating nerve. Our observations suggest a minimal burden for the animal with no signs of functional deficit in daily activities or auto-mutilation in both procedures. Furthermore, standard neurophysiological analyses for nerve and muscle regeneration were applicable. This newly developed nerve transfer model allows for the reliable and standardized investigation of neural and functional changes following the transfer of multiple donor nerves to one target muscle

Motor unit characteristics after selective nerve transfers

Selective nerve transfers are used in biological and bionic extremity reconstruction to restore and improve extremity function. Here, peripheral nerves are rerouted to various target muscles, and thereby the structural composition of motor units is surgically altered. Previous studies have shown a high success rate of successful reinnervation of above 90% after these nerve transfers. In targeted muscle reinnervation, nerve transfers are applied to reroute amputated nerves to more proximal muscles in the stump and thereby increase the number of prosthetic control signals. Because donor nerves physiologically supply multiple muscles but are transferred to a single target muscle, the innervation ratio between donor and recipient is substantially altered. This changes the characteristics of the motor unit of the target muscles that we extensively investigated in a novel nerve transfer animal model. In this chapter, we illustrate this model, the effect of nerve transfers on motor unit physiology, as well as the implications on improving the interface between man and machine in prosthetic extremity reconstruction. In addition, first results on the effect of targeted muscle reinnervation on human motor unit physiology are described