Regenerative peripheral nerve interfaces for real-time, proportional control of a Neuroprosthetic hand.

INTRODUCTION: Regenerative peripheral nerve interfaces (RPNIs) are biological constructs which amplify neural signals and have shown long-term stability in rat models. Real-time control of a neuroprosthesis in rat models has not yet been demonstrated. The purpose of this study was to: a) design and validate a system for translating electromyography (EMG) signals from an RPNI in a rat model into real-time control of a neuroprosthetic hand, and; b) use the system to demonstrate RPNI proportional neuroprosthesis control. METHODS: Animals were randomly assigned to three experimental groups: (1) Control; (2) Denervated, and; (3) RPNI. In the RPNI group, the extensor digitorum longus (EDL) muscle was dissected free, denervated, transferred to the lateral thigh and neurotized with the residual end of the transected common peroneal nerve. Rats received tactile stimuli to the hind-limb via monofilaments, and electrodes were used to record EMG. Signals were filtered, rectified and integrated using a moving sample window. Processed EMG signals (iEMG) from RPNIs were validated against Control and Denervated group outputs. RESULTS: Voluntary reflexive rat movements produced signaling that activated the prosthesis in both the Control and RPNI groups, but produced no activation in the Denervated group. Signal-to-Noise ratio between hind-limb movement and resting iEMG was 3.55 for Controls and 3.81 for RPNIs. Both Control and RPNI groups exhibited a logarithmic iEMG increase with increased monofilament pressure, allowing graded prosthetic hand speed control (R2 = 0.758 and R2 = 0.802, respectively). CONCLUSION: EMG signals were successfully acquired from RPNIs and translated into real-time neuroprosthetic control. Signal contamination from muscles adjacent to the RPNI was minimal. RPNI constructs provided reliable proportional prosthetic hand control.

Selective Thumb Carpometacarpal Joint Denervation for Painful Arthritis: Follow-Up of Long-Term Clinical Outcomes.

Purpose: Thumb carpometacarpal (CMC) joint osteoarthritis is a common problem affecting up to 85% of patients over the age of 70. The most common presenting symptom for patients with CMC arthritis is pain with joint loading. Loss of function due to subluxation or joint destruction is comparatively rare. Carpometacarpal joint denervation is a relatively novel method for managing CMC arthritis, treating the most impactful symptom: pain. Methods: In this paper, we present a 4- to 6-year follow-up case series on patients who underwent CMC denervation between 2015 and 2017. Results: Denervation was safe, with less downtime than trapeziectomy with ligament reconstruction with tendon interposition and provided durable complete or partial relief of pain after 5 years in 5 of 9 patients. Four of 9 patients had recurrence of pain by 5 years. Of those with recurrent pain, 3 of 5 eventually underwent trapeziectomy with ligament reconstruction and tendon interposition; the secondary surgery occurred between 17 and 66 months after denervation. Conclusion: Thumb CMC denervation provides effective relief of arthritis pain that was durable at 5+ years after surgery in more than half of our initial cohort of patients treated. Prospective studies with validated patient-reported and objective outcome measures between distinct treatment arms, such as denervation versus ligament reconstruction with tendon interposition, are needed to firmly establish the role of CMC denervation for patients with symptomatic thumb CMC osteoarthritis. Type of study/level of evidence: Therapeutic/Level IV.

Latissimus Dorsi Myocutaneous Flap Procedure in a Swine Model.

BACKGROUND: As surgical research expands in both breadth and scope, translational models become increasingly important. The accessibility, reproducibility, and clinical applicability of translational models is of vital importance to ensure adequate and accurate research. Though different flap models have been described, the literature lacks an in-depth, technical description of an easy large-animal preclinical model. We here describe the procedure for elevation of a latissimus dorsi flap in a swine. This flap contains muscle and skin that can be isolated on a vascular pedicle, transferred as a free flap, perfused, or innervated/denervated as dictated by the needs of the experiment. METHODS: Five different latissimus dorsi flaps were elevated in miniature swine. Careful attention was paid to anatomical landmarks and optimal placement of incision, dissection, and retraction. Temporary ischemia with vascular clamping was performed along with serial digital and infrared imaging both intra- and postoperatively. In three of the flaps with induced ischemia, the animal was observed for a 30-day follow up with daily photodocumentation and intermittent biopsy. RESULTS: A reproducible latissimus flap model was designed with optimized conditions. In the animals in which flaps were followed postoperatively, complete healing was seen within 30 days without evidence of procedure-related ischemia or loss of motor function. CONCLUSION: We have identified and described a pre-clinical large animal flap model that can be easily reproduced for translational studies of multiple scientific areas including flap-based repair, ischemia, ischemia reperfusion, and operative technique. This provides an important model for ready replication in preclinical studies of many varieties.

Resident workload, pager communications, and quality of care.

With the recent regulations limiting resident work hours, it has become more important to understand how residents spend their time. The volume and content of the pages they receive provide a valuable source of information that give insight into their workload and help identify inefficiencies in hospital communication. We hypothesized that above a certain workload threshold, paging data would suggest breakdowns in communication and implications for quality of care. All pages sent to six general surgery interns at the University of Michigan over the course of one academic year (7/1/2008-6/30/2009) were retrospectively categorized by sender type, message type, message modifier, and message quality. Census, discharge, and admission information for each intern service were also collected, and intern duties were further analyzed with respect to schedule. "On-call" days were defined as days on which the intern bore responsibility for care of all admitted floor patients. The interns received a total of 9,843 pages during the study period. During on-call shifts, each intern was paged an average of 57 ± 3 times, and those on non-call shifts received an average of 12 ± 3 pages. Floor/intensive care unit (ICU) nurses represented 32% of the page volume received by interns. Interestingly, as patient volume increased, there was a decrease in the number of pages received per patient. By contrast, at higher patient volumes, there was a trend toward an increasing percentage of urgent pages per patient. At high intern workloads, our data suggest no major communication breakdowns but reveal the potential for inferior quality of care.

Development of a Regenerative Peripheral Nerve Interface for Control of a Neuroprosthetic Limb.

Background. The purpose of this experiment was to develop a peripheral nerve interface using cultured myoblasts within a scaffold to provide a biologically stable interface while providing signal amplification for neuroprosthetic control and preventing neuroma formation. Methods. A Regenerative Peripheral Nerve Interface (RPNI) composed of a scaffold and cultured myoblasts was implanted on the end of a divided peroneal nerve in rats (n = 25). The scaffold material consisted of either silicone mesh, acellular muscle, or acellular muscle with chemically polymerized poly(3,4-ethylenedioxythiophene) conductive polymer. Average implantation time was 93 days. Electrophysiological tests were performed at endpoint to determine RPNI viability and ability to transduce neural signals. Tissue samples were examined using both light microscopy and immunohistochemistry. Results. All implanted RPNIs, regardless of scaffold type, remained viable and displayed robust vascularity. Electromyographic activity and stimulated compound muscle action potentials were successfully recorded from all RPNIs. Physiologic efferent motor action potentials were detected from RPNIs in response to sensory foot stimulation. Histology and transmission electron microscopy revealed mature muscle fibers, axonal regeneration without neuroma formation, neovascularization, and synaptogenesis. Desmin staining confirmed the preservation and maturation of myoblasts within the RPNIs. Conclusions. RPNI demonstrates significant myoblast maturation, innervation, and vascularization without neuroma formation.

Decellular biological scaffold polymerized with PEDOT for improving peripheral nerve interface charge transfer.

Regenerative peripheral nerve interfaces (RPNIs) are for signal transfer between peripheral nerves inside the body to controllers for motorized prosthetics external to the body. Within the residual limb of an amputee, surgical construction of a RPNI connects a remaining peripheral nerve and spare muscle. Nerve signals become concentrated within the RPNI. Currently metal electrodes implanted on the RPNI muscle transfer signals but scarring around metal electrodes progressively diminishes charge transfer. Engineered materials may benefit RPNI signal transfer across the neural interface if they lower the power and charge density of the biologically meaningful signals. Poly3,4-ethylenedioxythiophene (PEDOT) is known to mediate ionic potentials allowing excitation across a critical nerve gap. We hypothesize that the capacity of an interface material to conduct electron mediated current is significantly increased by polymerized coating of PEDOT. SIS was either used plain or after PEDOT coating by electrochemical polymerization. Muscle forces are a direct representation of stimulating current distribution within an RPNI. In situ muscle forces were measured for the same muscle by electrically stimulating: a) the muscle's innervating nerve, b) directly on the muscle, c) on plain SIS laid on the muscle, and d) on SIS polymerized with PEDOT laid on the muscle. Electro-chemically coating PEDOT on SIS resulted in a thin, flexible material. PEDOT coated SIS distributed electrical stimulation more efficiently than SIS alone. Conductive polymer containing biological material allowed ionic signal distribution within the RPNI like muscle at lower charge density.

PEDOT electrochemical polymerization improves electrode fidelity and sensitivity.

BACKGROUND: The goal of the authors is to restore fine motor control and sensation for high-arm amputees. They developed a regenerative peripheral nerve interface with the aim of attaining closed loop neural control by integrating directly with the amputee's residual motor and sensory peripheral nerves. PEDOT, poly(3,4-ethylenedioxythiophene), has both electrical and ionic conduction characteristics. This hybrid character could help bridge the salutatory conduction of the nervous system to an electrode. The purpose of this study was to determine whether electrodes polymerized with PEDOT have improved ability to both record and stimulate peripheral nerve action potentials. METHODS: Impedance spectroscopy and cyclic voltammetry were performed on electrodes before and after polymerization to measure electrode impedance and charge capacity. Both recording needle and bipolar stimulating electrodes were polymerized with PEDOT. Plain and PEDOT electrodes were tested using rat (n = 18) in situ nerve conduction studies. The peroneal nerve was stimulated using a bipolar electrode at multiple locations along the nerve. Action potentials were measured in the extensor digitorum longus muscle. RESULTS: Bench testing showed PEDOT electrodes had a higher charge capacity and lower impedance than plain electrodes, indicating significantly improved electrode fidelity. Nerve conduction testing indicated a significant reduction in the stimulus threshold for both PEDOT recording and PEDOT stimulatory electrodes when compared with plain electrodes, indicating an increase in sensitivity. CONCLUSIONS: PEDOT electrochemical polymerization improves electrode fidelity. Electrodes that have been electropolymerized with PEDOT show improved sensitivity when recording or stimulating action potentials at the tissue-electrode interface.