A novel functional electrical stimulation sleeve based on textile-embedded dry electrodes.

BACKGROUND: Functional electrical stimulation (FES) is a rehabilitation technique that enables functional improvements in patients with motor control impairments. This study presents an original design and prototyping method for a smart sleeve for FES applications. The article explains how to integrate a carbon-based dry electrode into a textile structure and ensure an electrical connection between the electrodes and the stimulator for effective delivery of the FES. It also describes the materials and the step-by-step manufacturing processes. RESULTS: The carbon-based dry electrode is integrated into the textile substrate by a thermal compression molding process on an embroidered conductive matrix. This matrix is composed of textile silver-plated conductive yarns and is linked to the stimulator. Besides ensuring the electrical connection, the matrix improves the fixation between the textile substrate and the electrode. The stimulation intensity, the perceived comfort and the muscle torque generated by the smart FES sleeve were compared to hydrogel electrodes. The results show a better average comfort and a higher average stimulation intensity with the smart FES sleeve, while there were no significant differences for the muscle torque generated. CONCLUSIONS: The integration of the proposed dry electrodes into a textile is a viable solution. The wearable FES system does not negatively impact the electrodes' performance, and tends to improve it. Additionally, the proposed prototyping method is applicable to an entire garment in order to target all muscles. Moreover, the process is feasible for industrial production and commercialization since all materials and processes used are already available on the market.

Cryogel-based neurostimulation electrodes to activate endogenous neural precursor cells.

The delivery of electrical pulses to the brain via penetrating electrodes, known as brain stimulation, has been recognized as an effective clinical approach for treating neurological disorders. Resident brain neural precursor cells (NPCs) are electrosensitive cells that respond to electrical stimulation by expanding in number, migrating and differentiating which are important characteristics that support neural repair. Here, we report the design of a conductive cryogel brain stimulation electrode specifically developed for NPC activation. The cryogel electrode has a modulus switching mechanism permitting facile penetration and reducing the mechanical mismatch between brain tissue and the penetrating electrode. The cryogel demonstrated good in vivo biocompatibility and reduced the interfacial impedance to deliver the stimulating electric field with lower voltage under charge-balanced current controlled stimulation. An ex vivo assay reveals that electrical stimulation using the cryogel electrodes results in significant expansion in the size of NPC pool. Hence, the cryogel electrodes have the potential to be used for NPC activation to support endogenous neural repair. STATEMENT OF SIGNIFICANCE: The objective of this study is to develop a cryogel-based stimulation electrode as an alternative to traditional electrode materials to be used in regenerative medicine applications for enhancing neural regeneration in brain. The electrode offers benefits such as adaptive modulus for implantation, high charge storage and injection capacities, and modulus matching with brain tissue, allowing for stable delivery of electric field for long-term neuromodulation. The electrochemical properties of cryogel electrodes were characterized in living tissue with an ex vivo set-up, providing a deeper understanding of stimulation capacity in brain environments. The cryogel electrode is biocompatible and enables low voltage, current-controlled stimulation for effective activation of endogenous neural precursor cells, revealing their potential utility in neural stem cell-mediated brain repair.

Manipulating facial musculature with functional electrical stimulation as an intervention for major depressive disorder: a focused search of literature for a proposal.

BACKGROUND: Major Depressive Disorder (MDD) is associated with interoceptive deficits expressed throughout the body, particularly the facial musculature. According to the facial feedback hypothesis, afferent feedback from the facial muscles suffices to alter the emotional experience. Thus, manipulating the facial muscles could provide a new "mind-body" intervention for MDD. This article provides a conceptual overview of functional electrical stimulation (FES), a novel neuromodulation-based treatment modality that can be potentially used in the treatment of disorders of disrupted brain connectivity, such as MDD. METHODS: A focused literature search was performed for clinical studies of FES as a modulatory treatment for mood symptoms. The literature is reviewed in a narrative format, integrating theories of emotion, facial expression, and MDD. RESULTS: A rich body of literature on FES supports the notion that peripheral muscle manipulation in patients with stroke or spinal cord injury may enhance central neuroplasticity, restoring lost sensorimotor function. These neuroplastic effects suggest that FES may be a promising innovative intervention for psychiatric disorders of disrupted brain connectivity, such as MDD. Recent pilot data on repetitive FES applied to the facial muscles in healthy participants and patients with MDD show early promise, suggesting that FES may attenuate the negative interoceptive bias associated with MDD by enhancing positive facial feedback. Neurobiologically, the amygdala and nodes of the emotion-to-motor transformation loop may serve as potential neural targets for facial FES in MDD, as they integrate proprioceptive and interoceptive inputs from muscles of facial expression and fine-tune their motor output in line with socio-emotional context. CONCLUSIONS: Manipulating facial muscles may represent a mechanistically novel treatment strategy for MDD and other disorders of disrupted brain connectivity that is worthy of investigation in phase II/III trials.

A novel ex vivo assay to define charge-balanced electrical stimulation parameters for neural precursor cell activation in vivo.

Endogenous neural stem cells and their progeny (together termed neural precursor cells (NPCs)) are promising candidates to facilitate neuroregeneration. Charge-balanced biphasic monopolar stimulation (BPMP) is a clinically relevant approach that can activate NPCs both in vitro and in vivo. Herein, we established a novel ex vivo stimulation system to optimize the efficacy of BPMP electric field (EF) application in activating endogenous NPCs. Using the ex vivo system, we discerned that cathodal amplitude of 200 µA resulted in the greatest NPC pool expansion and enhanced cathodal migration. Application of the same stimulation parameters in vivo resulted in the same NPC activation in the mouse brain. The design and implementation of the novel ex vivo model bridges the gap between in vitro and in vivo systems, enabling a moderate throughput stimulation system to explore and optimize EF parameters that can be applied to clinically relevant brain injury/disease models.

The Orthotic Effects of Different Functional Electrical Stimulation Protocols on Walking Performance in Individuals with Incomplete Spinal Cord Injury: A Case Series.

Background: Functional electrical stimulation (FES) of paralyzed muscles can facilitate walking after spinal cord injury (SCI). Objectives: To test the orthotic effects of different FES walking protocols on lower joint kinematics and walking speed. Methods: Three adults with incomplete SCI participated in this study. Their lower extremity motor scores and 10-meter walk test results were as follows: subject A: 50, 1.05 m/s, subject B: 44, 0.29 m/s, and subject C: 32, 0.27 m/s. Participants completed four conditions of over-ground walking including no FES and three bilateral FES-walking protocols as follows: multi-muscle stimulation (stimulation of quadriceps and gastrocnemius in the stance phase, and hamstring and tibialis anterior in the swing phase), drop foot (tibialis anterior stimulation), and flexor withdrawal (common peroneal nerve stimulation). The FES system obtained gait phase information from foot switches located under the individuals' heels. Three-dimensional kinematic analysis was undertaken to measure minimum toe clearance (MTC); ankle, knee, and hip range of motion (ROM); stride length; and stride speed. Results: Compared to no-FES walking, MTC increased during drop foot (all subjects), flexor withdrawal (subjects A and B), and multi-muscle stimulation (subjects B and C) protocols. A significant decrease in ankle ROM was seen with drop foot (all subjects), flexor withdrawal (subjects A), and multi-muscle stimulation (subjects A and C) protocols. Hip ROM increased with drop foot (subjects B and C), flexor withdrawal (subject B), and multi-muscle stimulation (subject C) protocols. Conclusion: Three FES walking protocols induced positive kinematic changes as indicated by increased MTC, decreased ankle ROM, and increased hip ROM during walking in subjects with incomplete SCI.

Facile Fabrication of Injectable Alginate and Poly(3,4-ethylenedioxythiophene)-Based Soft Electrodes toward the Goal of Neuro-Regenerative Applications.

Resident brain neural precursor cells (NPCs) are electrosensitive cells that respond to electric field application by proliferating, differentiating, and undergoing rapid and directed cathodal migration. Harnessing NPC potential is a promising strategy to facilitate neural repair following injury or disease. The use of electric fields to activate NPCs is limited by current electrode designs which are typically made of conductive metals that are stiff and can lead to neuroinflammation following implantation, in part due to the mechanical mismatch between physiological conditions and material. Herein, the design of a novel, injectable biobased soft electrode with properties suitable for electrical stimulation in vivo is explored. The recent interest in using biologically derived polymers which are relatively abundant and afford economic feasibility have been built upon. Sodium alginate is utilized to form soft hydrogels, thereby addressing the issue of mechanical mismatch, and the conductive polymer, poly(3,4-ethylenedioxythiophene) (PEDOT), to generate an innovative new material. It is demonstrated that the optimized alginate PEDOT blend matches the modulus of the brain and is suitable for injection and is not cytotoxic to neural cells. Furthermore, in vivo studies demonstrate minimal activation of inflammatory cells upon implantation in the brain compared to classically used platinum-based electrodes.

Electric Field Application In Vivo Regulates Neural Precursor Cell Behavior in the Adult Mammalian Forebrain.

Deep brain stimulation (DBS), which uses electrical stimulation, is a well-established neurosurgical technique used to treat neurologic disorders. Despite its broad therapeutic use, the effects of electrical stimulation on brain cells is not fully understood. Here, we examine the effects of electrical stimulation on neural stem and progenitor cells (collectively neural precursor cells; NPCs) from the subventricular zone in the adult forebrain of C57BL/6J mice. Previous work has demonstrated that adult-derived NPCs are electro sensitive and undergo rapid and directed migration in response to application of clinically relevant electric fields (EFs). We examine NPC proliferation kinetics and their differentiation profile following EF application using in vitro and in vivo assays. In vitro direct current electrical stimulation of 250 mV/mm is sufficient to elicit a 2-fold increase in the neural stem cell pool and increases neurogenesis and oligogenesis. In vivo, asymmetric biphasic electrical stimulation similarly increases the size of the NPC pool and alters neurogenesis. These findings provide insight into the effects of electrical stimulation on NPCs and suggest its potential use as a regenerative approach to neural repair.

Novel Electrode Designs for Neurostimulation in Regenerative Medicine: Activation of Stem Cells.

Neural stem and progenitor cells (i.e., neural precursors) are found within specific regions in the central nervous system and have great regenerative capacity. These cells are electrosensitive and their behavior can be regulated by the presence of electric fields (EFs). Electrical stimulation is currently used to treat neurological disorders in a clinical setting. Herein we propose that electrical stimulation can be used to enhance neural repair by regulating neural precursor cell (NPC) kinetics and promoting their migration to sites of injury or disease. We discuss how intrinsic and extrinsic factors can affect NPC migration in the presence of an EF and how this impacts electrode design with the goal of enhancing tissue regeneration. We conclude with an outlook on future clinical applications of electrical stimulation and highlight technological advances that would greatly support these applications.

Substrate-Dependent Galvanotaxis of Directly Reprogrammed Human Neural Precursor Cells.

Background: Neural precursor cells (NPCs) hold great promise for neural repair. Endogenous NPCs, found in the subventricular zone of the adult brain, proliferate and migrate toward lesion sites; however, it is not sufficient for neural repair. NPCs are electrosensitive cells that undergo directed migration in an electric field (EF). Here, we examined the EF-induced migration of a clinically relevant human NPC population. Materials & Methods: We examined the effects of different substrates and microenvironments on human NPC galvanotaxis. Results: Human NPCs increased their migration speed in the presence of an EF, and the direction of migration (anodal vs. cathodal) varied between substrates. The secretome and extracellular pH were not significant factors in EF-induced migration; however, our results are consistent with substrate stiffness playing a role in the direction of cell migration. Conclusion: These findings provide insight into the importance of the microenvironment on modulating human NPC migration and highlight substrate-dependent considerations for neurorepair.

Charge-Balanced Electrical Stimulation Can Modulate Neural Precursor Cell Migration in the Presence of Endogenous Electric Fields in Mouse Brains.

Electric fields (EFs) can direct cell migration and are crucial during development and tissue repair. We previously reported neural precursor cells (NPCs) are electrosensitive cells that can undergo rapid and directed migration towards the cathode using charge-balanced electrical stimulation in vitro Here, we investigate the ability of electrical stimulation to direct neural precursor migration in mouse brains in vivo To visualize migration, fluorescent adult murine neural precursors were transplanted onto the corpus callosum of adult male mice and intracortical platinum wire electrodes were implanted medial (cathode) and lateral (anode) to the injection site. We applied a charge-balanced biphasic monopolar stimulation waveform for three sessions per day, for 3 or 6 d. Irrespective of stimulation, the transplanted neural precursors had a propensity to migrate laterally along the corpus callosum, and applied stimulation affected that migration. Further investigation revealed an endogenous EF along the corpus callosum that correlated with the lateral migration, suggesting that the applied EF would need to overcome endogenous cues. There was no difference in transplanted cell differentiation and proliferation, or inflammatory cell numbers near the electrode leads and injection site comparing stimulated and implanted non-stimulated brains. Our results support that endogenous and applied EFs are important considerations for designing cell therapies for tissue repair in vivo.

Skin-derived precursor cells undergo substrate-dependent galvanotaxis that can be modified by neighbouring cells.

Many cell types respond to electric fields (EFs) through cell migration, a process termed galvanotaxis. The galvanotactic response is critical for development and wound healing. Here we investigate whether skin-derived precursor cells (SKPs), which have the potential to differentiate into mesodermal and peripheral neural cell types, undergo directed migration in the presence of an EF. We found that EF application promotes SKP migration towards the anode. The migratory response is substrate-dependent as SKPs undergo directed migration on laminin and Matrigel, but not collagen. The majority of SKPs express the undifferentiated cell markers nestin, fibronectin and Sox2, after both EF application and in sister cultures with no EF application, suggesting that EFs do not promote cell differentiation. Co-cultures of SKPs and brain-derived neural precursor cells (NPCs), a population of cells that undergo rapid, cathode-directed migration, reveal that in the presence of NPCs an increased percentage of SKPs undergo galvanotaxis, providing evidence that cells can provide cues to modify the galvanotactic response. We propose that a better understanding of SKP migration in the presence of EFs may provide insight into improved strategies for wound repair.

Environmental Factors That Influence Stem Cell Migration: An "Electric Field".

Environmental Stimulus of Electric Fields on Stem Cell Migration. The movement of cells in response to electric potential gradients is called galvanotaxis. In vivo galvanotaxis, powered by endogenous electric fields (EFs), plays a critical role during development and wound healing. This review aims to provide a perspective on how stem cells transduce EFs into directed migration and an understanding of the current literature relating to the mechanisms by which cells sense and transduce EFs. We will comment on potential EF-based regenerative medicine therapeutics.