Objective Spinal cord injury causes a drastic loss of motor, sensory and autonomic function. The goal of this project was to investigate the use of intraspinal microstimulation (ISMS) for producing long distances of walking over ground. ISMS is an electrical stimulation method developed for restoring motor function by activating spinal networks below the level of an injury. It produces movements of the legs by stimulating the ventral horn of the lumbar enlargement using fine penetrating electrodes (≤ 50µm diameter). Approach In each of five adult cats (4.2–5.5kg), ISMS was applied through 16 electrodes implanted with tips targeting lamina IX in the ventral horn bilaterally. A desktop system implemented a physiologically-based control strategy that delivered different stimulation patterns through groups of electrodes to evoke walking movements with appropriate limb kinematics and forces corresponding to swing and stance. Each cat walked over an instrumented 2.9m walkway and limb kinematics and forces were recorded. Main Results Both propulsive and supportive forces were required for over-ground walking. Cumulative walking distances ranging from 609m to 835m (longest tested) were achieved in three animals. In these three cats, the mean peak supportive force was 3.5±0.6N corresponding to full-weight-support of the hind legs, while the angular range of the hip, knee, and ankle joints were 23.1±2.0°, 29.1±0.2°, and 60.3±5.2°, respectively. To further demonstrate the viability of ISMS for future clinical use, a prototype implantable module was successfully implemented in a subset of trials and produced comparable walking performance. Significance By activating inherent locomotor networks within the lumbosacral spinal cord, ISMS was capable of producing bilaterally coordinated and functional over-ground walking with current amplitudes <100 µA. These exciting results suggest that ISMS may be an effective intervention for restoring functional walking after spinal cord injury.

The overall goal of this work was to create a high-resolution MRI atlas of the lumbosacral enlargement of the spinal cord of the rat (Sprague–Dawley), cat, domestic pig, rhesus monkey, and human. These species were chosen because they are commonly used in basic and translational research in spinal cord injuries and diseases. Six spinal cord specimens from each of the studied species (total of 30 specimens) were fixed, extracted, and imaged. Sizes of the spinal cord segments, cross-sectional dimensions, and locations of the spinal cord gray and white matter were quantified and compared across species. The lumbar enlargement spans spinal cord levels L3-S1 in rats, L4-S1 in cats, L3-S1 in pigs, L2/L3-L7/S1 in monkeys, and T12/L1-S1/S2 in humans. The enlargements in pigs and humans are largest and most similar in size (length and cross-sectional area); followed by monkeys and cats; and followed by rats. The obtained atlas establishes a neuroanatomical reference for the intact lumbosacral spinal cord in these species. It can also be used to guide the planning of surgical procedures of the spinal cord and technology design and development of spinal cord neuroprostheses, as well as precise delivery of cells/drugs into target regions within the spinal cord parenchyma.

Spinal cord injury (SCI) leads to chronic and multifaceted disability, which severely impacts the physical and mental health as well as the socio-economic status of affected individuals. Permanent disabilities following SCI result from the failure of injured neurons to regenerate and rebuild functional connections with their original targets. Inhibitory factors present in the SCI microenvironment and the poor intrinsic regenerative capacity of adult spinal cord neurons are obstacles for regeneration and functional recovery. Considerable progress has been made in recent years in developing cell and molecular approaches to enable the regeneration of damaged spinal cord tissue. In this review, we highlight several potent cell-based approaches and genetic manipulation strategies (gene therapy) that are being investigated to reconstruct damaged or lost spinal neural circuits and explore emerging novel combinatorial approaches for enhancing recovery from SCI.

Implantable spinal-cord-neuroprostheses aiming to restore standing and walking after paralysis have been extensively studied in animal models (mainly cats) and have shown promising outcomes. This study aimed to take a critical step along the clinical translation path of these neuroprostheses, and investigated the organization of the neural networks targeted by these implants in a non-human primate. This was accomplished by advancing a microelectrode into various locations of the lumbar enlargement of the spinal cord, targeting the ventral horn of the gray matter. Microstimulation in these locations produced a variety of functional movements in the hindlimb. The resulting functional map of the spinal cord in monkeys was found to have a similar overall organization along the length of the spinal cord to that in cats. This suggests that the human spinal cord may also be organized similarly. The obtained spinal cord maps in monkeys provide important knowledge that will guide the very first testing of these implants in humans.

The goal of this study was to develop stable intraspinal microstimulation (ISMS) implants for use in humans to restore standing and walking after spinal cord injury. ISMS electrically activates locomotor networks within the lumbar region of the spinal cord. In animals, ISMS produced better functional outcomes than those obtained by other interventions, and recent efforts have focused on translating this approach to humans. This study used domestic pigs to: (1) quantify the movements and length changes of the implant region of the spinal cord during spine flexion and extension movements; and (2) measure the forces leading to the dislodgement of the ISMS electrodes. The displacement of the spinal cord implant region was 5.66 ± 0.57 mm relative to the implant fixation point on the spine. The overall length change of the spinal cord implant region was 5.64 ± 0.59 mm. The electrode dislodgment forces were 60.9 ± 35.5 mN. Based on these results, six different coil types were fabricated and their strain relief capacity assessed. When interposed between the electrodes and the stimulator, five coil types successfully prevented the dislodgement of the electrodes. The results of this study will guide the design of mechanically stable ISMS implants for ultimate human use.

OBJECTIVEThe overall goal of this study was to develop an image-guided spinal stereotactic setup for intraoperative intraspinal microstimulation (ISMS). System requirements were as follows: 1) ability to place implants in various segments of the spinal cord, targeting the gray matter with a < 0.5-mm error; 2) modularity; and 3) compatibility with standard surgical tools.METHODSA spine-mounted stereotactic system was developed, optimized, and tested in pigs. The system consists of a platform supporting a micromanipulator with 6 degrees of freedom. It is modular and flexible in design and can be applied to various regions of the spine. An intraoperative ultrasound imaging technique was also developed and assessed for guidance of electrode alignment prior to and after electrode insertion into the spinal cord. Performance of the ultrasound-guided stereotactic system was assessed both in pigs (1 live and 6 fresh cadaveric pigs) and on the bench using four gelatin-based surrogate spinal cords. Pig experiments were conducted to evaluate the performance of ultrasound imaging in aligning the electrode trajectory using three techniques and under two conditions. Benchtop experiments were performed to assess the performance of ultrasound-guided targeting more directly. These experiments were used to quantify the accuracy of electrode alignment as well as assess the accuracy of the implantation depth and the error in spatial targeting within the gray matter of the spinal cord. As proof of concept, an intraoperative ISMS experiment was also conducted in an additional live pig using the stereotactic system, and the resulting movements and electromyographic responses were recorded.RESULTSThe stereotactic system was quick to set up (< 10 minutes) and provided sufficient stability and range of motion to reach the ISMS targets reliably in the pigs. Transverse ultrasound images with the probe angled at 25°–45° provided acceptable contrast between the gray and white matter of the spinal cord. In pigs, the largest electrode alignment error using ultrasound guidance, relative to the minor axis of the spinal cord, was ≤ 3.57° (upper bound of the 95% confidence interval). The targeting error with ultrasound guidance in bench testing for targets 4 mm deep into the surrogate spinal cords was 0.2 ± 0.02 mm (mean ± standard deviation).CONCLUSIONSThe authors developed and evaluated an ultrasound-guided spinal stereotactic system for precise insertion of intraspinal implants. The system is compatible with existing spinal instrumentation. Intraoperative ultrasound imaging of the spinal cord aids in alignment of the implants before insertion and provides feedback during and after implantation. The ability of ultrasound imaging to distinguish between spinal cord gray and white matter also improves confidence in the localization of targets within the gray matter. This system would be suitable for accurate guidance of intraspinal electrodes and drug or cell injections.

Recent advances in telemedicine and personalized healthcare have motivated new developments in wearable technologies targeting continuous monitoring of biosignals. Common limitations of wearables for continuous monitoring include durability and breathability of their biopotential electrodes. This paper tackles this challenge by proposing flexible, breathable, and washable dry textile electrodes made of conductive elastomeric filaments (CEFs). First, candidate CEF fibers are characterized. Using an industrial knitting machine, CEF fibers are then directly knitted into textile electrodes. To assess their performance in more realistic circumstances, smart garments with textile electrodes are knitted. Electrocardiograms (ECGs) are acquired using an underwear garment and electrooculograms (EOGs) are acquired using a headband. ECGs and EOGs with textile electrodes are found to have comparable fidelity to that of the gold standard gel electrodes. CEF electrodes are also resistant to repeated wash and dry cycles (30×) and continue to acquire high‐fidelity biosignals. Smart underwear garments are also used to perform continuous ECG measurements in five participants over 24 h of unrestricted daily activities. Results demonstrate the success of these garments in performing high fidelity continuous ECG monitoring. Collectively, these results present CEF electrodes as a promising scalable solution to the challenges of wearable technologies for long‐term continuous electrophysiological monitoring applications.

In this paper, a novel low-cost, rapid substrate-bonding technique is successfully applied to polymethyl methacrylate (PMMA) microfluidics bonding for the first time. This technique uses a thin intermediate metallic microwave susceptor layer at the interface of the bonding site (microchannels) which produces localized heating required for bonding during microwave irradiation. The metallic susceptor pattern is designed using a multiphysics simulation model developed in ANSYS Multiphysics software (high-frequency structural simulation (HFSS) coupled with ANSYS-Thermal). In our experiments, the required microwave energy for bonding is delivered using a relatively inexpensive, widely accessible commercial microwave oven. Using this technique, simple PMMA microfluidics prototypes are successfully bonded and sealed in less than 35 seconds with a minimum measured bond strength of 1.375 MPa.