Biologic scaffolds composed of naturally occurring extracellular matrix (ECM) can provide a microenvironmental niche that alters the default healing response toward a constructive and functional outcome. The present study showed similarities in the remodeling characteristics of xenogeneic ECM scaffolds when used as a surgical treatment for volumetric muscle loss in both a preclinical rodent model and five male patients. Porcine urinary bladder ECM scaffold implantation was associated with perivascular stem cell mobilization and accumulation within the site of injury, and de novo formation of skeletal muscle cells. The ECM-mediated constructive remodeling was associated with stimulus-responsive skeletal muscle in rodents and functional improvement in three of the five human patients.

Restoring somatosensory feedback to people with limb amputations is crucial to improve prosthetic control. Multiple studies have demonstrated that peripheral nerve stimulation and targeted reinnervation can provide somatotopically relevant sensory feedback. While effective, the surgical procedures required for these techniques remain a major barrier to translatability. Here, we demonstrate in four people with upper-limb amputation that epidural spinal cord stimulation (SCS), a common clinical technique to treat pain, evoked somatosensory percepts that were perceived as emanating from the missing arm and hand. Over up to 29 days, stimulation evoked sensory percepts in consistent locations in the missing hand regardless of time since amputation or level of amputation. Evoked sensations were occasionally described as naturalistic (e.g. touch or pressure), but were often paresthesias. Increasing stimulus amplitude increased the perceived intensity linearly, without increasing area of the sensations. These results demonstrate the potential of SCS as a tool to restore somatosensation after amputations.

Autonomic nerves are attractive targets for medical therapies using electroceutical devices because of the potential for selective control and few side effects. These devices use novel materials, electrode configurations, stimulation patterns, and closed-loop control to treat heart failure, hypertension, gastrointestinal and bladder diseases, obesity/diabetes, and inflammatory disorders. Critical to progress is a mechanistic understanding of multi-level controls of target organs, disease adaptation, and impact of neuromodulation to restore organ function.

This study describes the stability and selectivity of four-contact spiral nerve-cuff electrodes implanted bilaterally on distal branches of the femoral nerves of a human volunteer with spinal cord injury as part of a neuroprosthesis for standing and transfers. Stimulation charge threshold, the minimum charge required to elicit a visible muscle contraction, was consistent and low (mean threshold charge at 63 weeks post-implantation: 23.3 ± 8.5 nC) for all nerve-cuff electrode contacts over 63 weeks after implantation, indicating a stable interface with the peripheral nervous system. The ability of individual nerve-cuff electrode contacts to selectively stimulate separate components of the femoral nerve to activate individual heads of the quadriceps was assessed with fine-wire intramuscular electromyography while measuring isometric twitch knee extension moment. Six of eight electrode contacts could selectively activate one head of the quadriceps while selectively excluding others to produce maximum twitch responses of between 3.8 and 8.1 Nm. The relationship between isometric twitch and tetanic knee extension moment was quantified, and selective twitch muscle responses scaled to between 15 and 35 Nm in tetanic response to pulse trains with similar stimulation parameters. These results suggest that this nerve-cuff electrode can be an effective and chronically stable tool for selectively stimulating distal nerve branches in the lower extremities for neuroprosthetic applications.

This report describes the performance of a 16-channel implanted neuroprosthesis for standing and transfers after spinal cord injury including four-contact nerve-cuff electrodes stimulating the femoral nerve for knee extension. Responses of the nerve-cuffs were stable and standing times increased by 600% over time-matched values with a similar 8-channel neuroprosthesis utilizing muscle-based electrodes on vastus lateralis for knee extension.

Minimally invasive neuromodulation technologies seek to marry the neural selectivity of implantable devices with the low-cost and non-invasive nature of transcutaneous electrical stimulation (TES). The Injectrode® is a needle-delivered electrode that is injected onto neural structures under image guidance. Power is then transcutaneously delivered to the Injectrode using surface electrodes. The Injectrode serves as a low-impedance conduit to guide current to the deep on-target nerve, reducing activation thresholds by an order of magnitude compared to using only surface stimulation electrodes. To minimize off-target recruitment of cutaneous fibers, the energy transfer efficiency from the surface electrodes to the Injectrode must be optimized. TES energy is transferred to the Injectrode through both capacitive and resistive mechanisms. Electrostatic finite element models generally used in TES research consider only the resistive means of energy transfer by defining tissue conductivities. Here, we present an electroquasistatic model, taking into consideration both the conductivity and permittivity of tissue, to understand transcutaneous power delivery to the Injectrode. The model was validated with measurements taken from (n = 4) swine cadavers. We used the validated model to investigate system and anatomic parameters that influence the coupling efficiency of the Injectrode energy delivery system. Our work suggests the relevance of electroquasistatic models to account for capacitive charge transfer mechanisms when studying TES, particularly when high-frequency voltage components are present, such as those used for voltage-controlled pulses and sinusoidal nerve blocks.

Hydrogel-based electronics are ideally suited for neural interfaces because they exhibit ultracompliant mechanical properties that match that of excitable tissue in the brain and peripheral nerve. Hydrogel-based multielectrode arrays (MEA) can conformably interface with tissues to minimize inflammation and improve the reliability to enhance signal transduction.However, MEA substrates composed of swollen hydrogels exhibit low toughness and low adhesion stability when laminated on the tissue surface and also present technical challenges for processes commonly employed in MEA fabrication. Here, we describe a new strategy to fabricate ultracompliant MEA based on aqueous-phase transfer printing. This technique employs redox active adhesive motifs in hygroscopic polymer precursors that simultaneously form hydrogels through sol-gel phase transitions and bond to underlying microelectronic structures. Specifically, in situ gelation of 4-arm-polyethylene glycol-grafted catechol [PEG-Dopa]4 hydrogels induced by oxidation using Fe 3+ produces conformal adhesive contact with the underlying MEA, robust adhesion to electronic structures, and rapid dissolution of watersoluble sacrificial release layers. MEA are then integrated on hydrogel-based substrates to produce free standing ultracompliant neural probes, which are then laminated to the surface of the dorsal root ganglia in feline subjects to record single-unit neural activity.

A large proportion of cerebral strokes disrupt descending commands from motor cortical areas to the spinal cord which can results in permanent motor de cits of the arm and hand1,2. However, below the lesion, the spinal circuits that control movement5 remain intact and could be targeted by neurotechnologies to restore movement6-9. Here we demonstrate that by engaging spinal circuits with targeted electrical stimulation we immediately improved voluntary motor control in two participants with chronic post-stroke hemiparesis. We implanted a pair of 8-contact percutaneous epidural leads on the lateral aspect of the cervical spinal cord to selectively target the dorsal roots that provide excitatory inputs to motoneurons controlling the arm and hand10,11. With this strategy, we obtained independent activation of shoulder, elbow and hand muscles. Continuous stimulation through selected contacts at speci c frequencies enabled participants to perform movements that they had been unable to perform for many years. Overall, stimulation improved strength, kinematics, and functional performance.Unexpectedly, both participants retained some of these improvements even without stimulation, suggesting that spinal cord stimulation could be a restorative as well as an assistive approach for upper limb recovery after stroke.