Feasibility of endovascular stimulation of the femoral nerve using a stent-mounted electrode array.

Objective.Electrical stimulation of peripheral nerves has long been a treatment option to restore impaired neural functions that cannot be restored by conventional pharmacological therapies. Endovascular neurostimulation with stent-mounted electrode arrays is a promising and less invasive alternative to traditional implanted electrodes, which typically require invasive implantation surgery. In this study, we investigated the feasibility of endovascular stimulation of the femoral nerve using a stent-mounted electrode array and compared its performance to that of a commercially available pacing catheter.Approach.In acute animal experiments, a pacing catheter was implanted unilaterally in the femoral artery to stimulate the femoral nerve in a bipolar configuration. Electromyogram of the quadriceps and electroneurogram of a distal branch of the femoral nerve were recorded. After retrieval of the pacing catheter, a bipolar stent-mounted electrode array was implanted in the same artery and the recording sessions were repeated.Main Results.Stimulation of the femoral nerve was feasible with the stent-electrode array. Although the threshold stimulus intensities required with the stent-mounted electrode array (at 100-500µs increasing pulse width, 2.17 ± 0.87 mA-1.00 ± 0.11 mA) were more than two times higher than the pacing catheter electrodes (1.05 ± 0.48 mA-0.57 ± 0.28 mA), we demonstrated that, by reducing the stimulus pulse width to 100µs, the threshold charge per phase and charge density can be reduced to 0.22 ± 0.09µC and 24.62 ± 9.81µC cm-2, which were below the tissue-damaging limit, as defined by the Shannon criteria.Significance.The present study is the first to reportin vivofeasibility and efficiency of peripheral nerve stimulation using an endovascular stent-mounted electrode array.

Wireless electrostimulation for cancer treatment: An integrated nanoparticle/coaxial fiber mesh platform.

Cancer, namely breast and prostate cancers, is the leading cause of death in many developed countries. Controlled drug delivery systems are key for the development of new cancer treatment strategies, to improve the effectiveness of chemotherapy and tackle off-target effects. In here, we developed a biomaterials-based wireless electrostimulation system with the potential for controlled and on-demand release of anti-cancer drugs. The system is composed of curcumin-loaded poly(3,4-ethylenedioxythiophene) nanoparticles (CUR/PEDOT NPs), encapsulated inside coaxial poly(glycerol sebacate)/poly(caprolactone) (PGS/PCL) electrospun fibers. First, we show that the PGS/PCL nanofibers are biodegradable, which allows the delivery of NPs closer to the tumoral region, and have good mechanical properties, allowing the prolonged storage of the PEDOT NPs before their gradual release. Next, we demonstrate PEDOT/CUR nanoparticles can release CUR on-demand (65 % of release after applying a potential of -1.5 V for 180 s). Finally, a wireless electrostimulation platform using this NP/fiber system was set up to promote in vitro human prostate cancer cell death. We found a decrease of 67 % decrease in cancer cell viability. Overall, our results show the developed NP/fiber system has the potential to effectively deliver CUR in a highly controlled way to breast and prostate cancer in vitro models. We also show the potential of using wireless electrostimulation of drug-loaded NPs for cancer treatment, while using safe voltages for the human body. We believe our work is a stepping stone for the design and development of biomaterial-based future smarter and more effective delivery systems for anti-cancer therapy.

Comparison of Monopolar and Bipolar Stimulator Probes for Intraoperative Nerve Mapping During Thyroidectomy: A Prospective Study.

OBJECTIVES/HYPOTHESIS: During intraoperative neuromonitoring in thyroid surgery, two different kinds of stimulator probes, monopolar and bipolar, are commonly used to stimulate the laryngeal nerves. We explore the unique characteristics of both of these probes as they relate to intraoperative laryngeal nerve mapping. METHODS: Twenty-one patients undergoing neuromonitored thyroidectomy by a single surgeon were enrolled. Electromyography (EMG) amplitude and latency measurements were prospectively recorded concurrently from 1 mA stimulation of vagus nerve (VN) and inferior/superior recurrent laryngeal nerve before (with and without fascia) and after thyroid resection using bipolar and monopolar stimulator probes. RESULTS: Significantly higher amplitudes were obtained with monopolar stimulator probes as compared to bipolar probes, in several stimulation scenarios such as at right VN pre-resection (carotid sheath intact), right VN pre-resection (carotid sheath dissected), right VN post-resection and left VN (carotid sheath dissected). No significant differences were found between amplitudes and latency values in all other stimulation scenarios. CONCLUSIONS: According to this study, both probes are reliable and safe for neural mapping. The kind of probe used during neural monitoring is based on surgical situations and surgeon preference. LEVEL OF EVIDENCE: 3 (According to Oxford Centre for Evidence-Based Medicine 2011 Levels of Evidence) Laryngoscope, 131:E2718-E2726, 2021.

Endoscopic and Surgical Treatments for Gastroparesis: What to Do and Whom to Treat?

Gastroparesis is a complex chronic debilitating condition of gastric motility resulting in the delayed gastric emptying and multiple severe symptoms, which may lead to malnutrition and dehydration. Initial management of patients with gastroparesis focuses on the diet, lifestyle modification and medical therapy. Various endoscopic and surgical interventions are reserved for refractory cases of gastroparesis, not responding to conservative therapy. Pyloric interventions, enteral access tubes, gastric electrical stimulator and gastrectomy have been described in the care of patients with gastroparesis. In this article, the authors review current management, indications, and contraindications to these procedures.

Electric Fields at Breast Cancer and Cancer Cell Collective Galvanotaxis.

Cancer growth interferes with local ionic environments, membrane potentials, and transepithelial potentials, resulting in small electrical changes in the tumor microenvironment. Electrical fields (EFs) have significant effects on cancer cell migration (galvanotaxis/electrotaxis), however, their role as a regulator of cancer progression and metastasis is poorly understood. Here, we employed unique probe systems to characterize the electrical properties of cancer cells and their migratory ability under an EF. Subcutaneous tumors were established from a triple-negative murine breast cancer cell line (4T1), electric currents and potentials of tumors were measured using vibrating probe and glass microelectrodes, respectively. Steady outward and inward currents could be detected at different positions on the tumor surface and magnitudes of the electric currents on the tumor surface strongly correlated with tumor weights. Potential measurements also showed the non-homogeneous intratumor electric potentials. Cancer cell migration was then surveyed in the presence of EFs in vitro. Parental 4T1 cells and metastatic sublines in isolation showed random migration in EFs of physiological strength, whereas cells in monolayer migrated collectively to the anode. Our data contribute to an improved understanding of breast cancer metastasis, providing new evidence in support of an electrical mechanism that promotes this phenomenon.

Neuromonitored Thyroid Surgery: Optimal Stimulation Based on Intraoperative EMG Response Features.

OBJECTIVES: To evaluate/compare normative electrophysiologic electromyography (EMG) response characteristics of recurrent laryngeal, vagus, and external branch of superior laryngeal nerve evoked with different stimulators used in neuromonitored thyroid surgery. STUDY DESIGN: Prospective crossover study METHODS: EMG responses obtained via endotracheal tube surface electrodes in 11 patients undergoing thyroid surgery were recorded when stimulated with four stimulators: two monopolar (Prass standard and ball tip), one bipolar, and one dissecting instrument. Normative mean EMG results including latency, amplitude, threshold, saturation currents, and distance-sensitivity were compared. RESULTS: The Prass standard stimulator had shorter latency time when nerve was not covered with fascia (P = .04). The bipolar, dissecting instrument, and ball tip demonstrated similar latency times with and without nerve fascia. Pooled mean latency increased significantly from 1.86 ms to 2.16 ms when comparing nerves without fascia and nerves with fascia (P < .05). The Prass standard monopolar stimulator had the lowest mean threshold at 0.40 mA, with the dissecting instrument having the highest threshold at 0.89 mA for dissected nerve. Pooled mean threshold and saturation increased from 0.6 mA to 1.7 mA (P < .0001) and 1.57 mA to 4.15 mA (P < .001) with fascia covering nerve, respectively. The mean depolarization rate was 100% for monopolar and bipolar electrodes and 81% for dissecting instrument at 1 mA. Only 9% of monopolar electrodes generated an EMG response when stimulated from 2 mm away. CONCLUSION: Monopolar stimulators are more sensitive for neural mapping, whereas bipolar instruments are more specific, thus reducing false positive stimulation. Dissecting instruments share many features of monopolar stimulators while being more specific, and thus are a viable alternative. LEVEL OF EVIDENCE: 2b Laryngoscope, 2020.

Continuous Neural Monitoring in Endoscopic Thyroidectomy: Feasibility Experimental Study for Transcutaneous Vagal Nerve Stimulation.

Background: Adoption of continuous intraoperative neural monitoring (C-IONM) in endoscopic thyroid surgery is limited due to the uneasy application of C-IONM electrode. Feasibility for transcutaneous vagal nerve stimulation was tested. Materials and Methods: Vagus nerve (VN) and recurrent laryngeal nerve (RLN) were mapped and stimulated in different neck sites by (1) transcutaneous monopolar intermitted stimulation; (2) prototype for continuous transcutaneous stimulating electrodes (TSEs), that is, suction ball C-IONM electrode remodeled; (3) stimulation subsequently to neck CO2 insufflation; (4) direct stimulation of surgical exposed nerves. Electromyographic (EMG) parameters were compared. Results: Six anterior neck locations evoked EMG signals of VNs and RLNs. Location Nos. 3 and 6 according to our scheme were over the VNs, confirmed by ultrasonography and subsequent dissection. Other locations did not correspond to nerves sites. Transcutaneous thresholds were higher than surgical exposed ones to produce a consistent and satisfactory EMG response. TSE recorded solely in location No. 5 with amplitude values 256-9 µV. It was not possible to stimulate and monitor the RLN and VN after neck CO2 insufflation. Conclusion: Transcutaneous C-IONM is unfeasible for endoscopic thyroidectomy.

Stimulating and dissecting instrument for transoral endoscopic thyroidectomy: proof of concept investigation.

OBJECTIVES/HYPOTHESIS: Intraoperative neuromonitoring (IONM) is a useful adjunct for recurrent laryngeal nerve (RLN) mapping and identification in transoral endoscopic thyroidectomy vestibular approach (TOETVA). This experimental study aimed to investigate the feasibility, safety, thresholds required of an endoscopic forceps that combine the function of surgical dissection and nerve stimulation. STUDY DESIGN: Prospective experimental research. METHODS: TOETVA was performed in 12 piglets, i.e., 24 RLNs and 24 vagal nerves (VN). RLNs electromyography (EMG) was recorded via endotracheal surface electrodes. Baseline EMG of VN and RLN were recorded and compared by (a) percutaneously placed monopolar stimulator probe (Group I), (b) adapted Maryland endoscopic dissector applied on nerves at its tip-end (Group II) and (c) endoscopic dissector tip-lateral applied (Group III). EMG profiles, amplitude, latency, waveform, thresholds and supra-maximal stimulation (5 mA) were analyzed. RESULTS: Application of the endoscopic device was feasible in all TOETVA and did not result in any morbidity. 24 RLNs and VNs were detected, stimulated and monitored. With increase of stimulation current, the amplitude of EMG increased, showing a dose-response curve. Mean VN stimulation thresholds were: Group I 0.28 mA, Group II 0.56 mA, Group III 0.58 mA (P1 = 0.00, P2 = 0.00, P3 = 0.11). Minimal current to evoked a maximal VN response was: Group I 0.65 mA, Group II 1.07 mA and Group III 1.14 mA (P1 = 0.00, P2 = 0.00, P3 = 0.48). Minimal current to evoke a RLN maximal response was Group I 0.6 mA, Group II 0.95 mA and Group III 1.05 mA (P1 = 0.00, P2 = 0.00, P3 = 0.31). Latency values were similar to each group. Repetitive (> 10 min) supra-maximal (> 5 mA) electrical stimulation was safe. CONCLUSIONS: The application of endoscopic stimulating dissector is simple, effective and safe way to monitor both VN and RLN function during a TOETVA animal model. It provides surgeons with real-time feedback of EMG response and can be applied as a tool for RLN monitoring. Endoscopic instrument required higher current to evoke EMG response compared to hand probe stimulation. Tip-end required less current to evoke EMG response compared to tip-lateral mode of stimulation.

Photoelectric Cardiac Pacing by Flexible and Degradable Amorphous Si Radial Junction Stimulators.

Implanted pacemakers are usually bulky and rigid electronics that are constraint by limited battery lifetimes, and need to be installed and repaired via surgeries that risk secondary infection and injury. In this work, a flexible self-powered photoelectric cardiac stimulator is demonstrated based on hydrogenated amorphous Si (a-Si:H) radial p-i-n junctions (RJs), constructed upon standing Si nanowires grown directly on aluminum thin foils. The flexible RJ stimulators, with an open-circuit voltage of 0.67 V and short-circuit current density of 12.7 mA cm-2 under standard AM1.5G illumination, can be conformally attached to the uneven tissue surface to pace heart-beating under modulated 650 nm laser illumination. In vivo pacing evaluations on porcine hearts show that the heart rate can be effectively controlled by the external photoelectric stimulations, to increase from the normal rate of 101-128 beating min-1 . Importantly, the a-Si:H RJ units are highly biofriendly and biodegradable, with tunable lifetimes in phosphate-buffered saline environment controlled by surface coating and passivation, catering to the needs of short term or lasting cardiac pacing applications. This implantable a-Si:H RJ photoelectric stimulation strategy has the potential to establish eventually a self-powered, biocompatible, and conformable cardiac pacing technology for clinical therapy.

Continuous vestibular implant stimulation partially restores eye-stabilizing reflexes.

BACKGROUNDBilateral loss of vestibular (inner ear inertial) sensation causes chronically blurred vision during head movement, postural instability, and increased fall risk. Individuals who fail to compensate despite rehabilitation therapy have no adequate treatment options. Analogous to hearing restoration via cochlear implants, prosthetic electrical stimulation of vestibular nerve branches to encode head motion has garnered interest as a potential treatment, but prior studies in humans have not included continuous long-term stimulation or 3D binocular vestibulo-ocular reflex (VOR) oculography, without which one cannot determine whether an implant selectively stimulates the implanted ear's 3 semicircular canals.METHODSWe report binocular 3D VOR responses of 4 human subjects with ototoxic bilateral vestibular loss unilaterally implanted with a Labyrinth Devices Multichannel Vestibular Implant System vestibular implant, which provides continuous, long-term, motion-modulated prosthetic stimulation via electrodes in 3 semicircular canals.RESULTSInitiation of prosthetic stimulation evoked nystagmus that decayed within 30 minutes. Stimulation targeting 1 canal produced 3D VOR responses approximately aligned with that canal's anatomic axis. Targeting multiple canals yielded responses aligned with a vector sum of individual responses. Over 350-812 days of continuous 24 h/d use, modulated electrical stimulation produced stable VOR responses that grew with stimulus intensity and aligned approximately with any specified 3D head rotation axis.CONCLUSIONThese results demonstrate that a vestibular implant can selectively, continuously, and chronically provide artificial sensory input to all 3 implanted semicircular canals in individuals disabled by bilateral vestibular loss, driving reflexive VOR eye movements that approximately align in 3D with the head motion axis encoded by the implant.TRIAL REGISTRATIONClinicalTrials.gov: NCT02725463.FUNDINGNIH/National Institute on Deafness and Other Communication Disorders: R01DC013536 and 2T32DC000023; Labyrinth Devices, LLC; and Med-El GmbH.

Pressure Injuries Treated With Anodal and Cathodal High-voltage Electrical Stimulation: the Effect on Blood Serum Concentration of Cytokines and Growth Factors in Patients With Neurological Injuries. A Randomized Clinical Study.

It remains unclear whether electrical currents can affect biological factors that determine chronic wound healing in humans. PURPOSE: The aim of this study was to determine whether anodal and cathodal high-voltage monophasic pulsed currents (HVMPC) provided to the area of a pressure injury (PI) change the blood level of cytokines (interleukin [IL]-1ß, IL-10, and tumor necrosis factor [TNF]-α) and growth factors (insulin-like growth factor [IGF]-1 and transforming growth factor [TGF]-ß1) in patients with neurological injuries and whether the level of circulatory cytokines and growth factors correlates with PI healing progression. METHODS: This study was part of a randomized clinical trial on the effects of HVMPC on PI healing. All patients with neurological injuries (spinal cord injury, ischemic stroke, and blunt trauma to the head) and a stage 2, stage 3, or stage 4 PI of at least 4 weeks' duration hospitalized in one rehabilitation center were eligible to participate if older than 18 years of age and willing to consent to donating blood samples. Exclusion criteria included local contraindications to electrical stimulation (cancer, electronic implants, osteomyelitis, tunneling, necrotic wounds), PIs requiring surgical intervention, patients with poorly controlled diabetes mellitus (HbA1C > 7%), critical wound infection, and/or allergies to standard wound treatment. Participants were randomly assigned to 1 of 3 groups: anodal (AG) or cathodal (CG) HVMPC treatment (154 µs; 100 Hz; 360 µC/sec; 1.08 C/day) or a placebo (PG, sham) applied for 50 minutes a day, 5 days per week, for 8 weeks. TNF-α, IL-1ß, IL-10, TGF-ß1, and IGF-1 levels in blood serum were assessed using the immunoenzyme method (ELISA) and by chemiluminescence, respectively, at baseline and week 4. Wound surface area measurements were obtained at baseline and week 4 and analyzed using a digitizer connected to a personal computer. Statistical analyses were performed using the maximum-likelihood chi-squared test, the analysis of variance Kruskal-Wallis test, the Kruskal-Wallis post-hoc test, and Spearman's rank order correlation; the level of significance was set at P ≤.05. RESULTS: Among the 43 participants, 15 were randomized to AG (mean age 53.87 ± 13.30 years), 13 to CG (mean age 51.08 ± 20.43 years), and 15 to PG treatment (mean age 51.20 ± 14.47 years). Most PIs were located in the sacral region (12, 74.42%) and were stage 3 (11, 67.44%). Wound surface area baseline size ranged from 1.00 cm2 to 58.04 cm2. At baseline, none of the variables were significantly different. After 4 weeks, the concentration of IL-10 decreased in all groups (AG: 9.8%, CG: 38.54%, PG: 27.42%), but the decrease was smaller in the AG than CG group (P = .0046). The ratio of pro-inflammatory IL-10 to anti-inflammatory TNF-α increased 27.29% in the AG and decreased 26.79% in the CG and 18.56% in the PG groups. Differences between AG and CG and AG and PG were significant (AG compared to CG, P = .0009; AG compared to PG, P = .0054). Other percentage changes in cytokine and growth factor concentration were not statistically significant between groups. In the AG, the decrease of TNF-α and IL-1ß concentrations correlated positively with the decrease of PI size (P <.05). CONCLUSION: Anodal HVMPC elevates IL-10/TNF-α in blood serum. The decrease of TNF-α and IL-1ß concentrations in blood serum correlates with a decrease of PI wound area. More research is needed to determine whether the changes induced by anodal HVMPC improve PI healing and to determine whether and how different electrical currents affect the activity of biological agents responsible for specific wound healing phases, both within wounds and in patients' blood. In clinical practice, anodal HVMPC should be used to increase the ratio of anti-inflammatory IL-10 to pro-inflammatory TNF-α , which may promote healing.

Controlling ERK Activation Dynamics in Mammary Epithelial Cells with Alternating Electric Fields through Microelectrodes.

Amplitude, duration, and frequency of activation of the extracellular-signal-regulated kinase (ERK) pathway code distinct information to instruct cells to migrate, proliferate, or differentiate. Synchronized frequency control of ERK activation would provide a powerful approach to regulate cell behaviors. Here we demonstrated modulation of ERK activities using alternative current (AC) electric fields (EFs) applied through high-k dielectric passivated microelectrodes. Both the amplitude and frequency of ERK activation can be precisely synchronized and modulated. ERK activation in our system is independent of Faradaic currents and electroporation, thus excluding mechanisms of changes in pH, reactive oxygen species, and other electrochemical reaction. Further experiments pinpointed a mechanism of phosphorylation site of epidermal growth factor (EGF) receptor to activate the EGFR-ERK pathway, and independent of EGF. AC EFs thus provide a powerful platform for practical and precise control of EGFR-ERK pathway.

A novel microcurrent dressing for wound healing in a rat skin defect model.

BACKGROUND: The exogenous application of low-intensity electric stimulation (ES) may mimic a natural endogenous bioelectric current and accelerate the repair process of skin wounds. This study designed a novel microcurrent dressing (MCD) and evaluated its potential effects on wound healing in a rat skin defect model. METHODS: First, wireless ES was integrated into a medical cotton cushion to fabricate the MCD, and its electrical property was examined by using a universal power meter. Then, animal experiments were conducted to evaluate the MCD's effect. Forty-five rats were randomized into control (Con) group, Vaseline gauze (VG) group and MCD group. A full-thickness round skin incision 1.5 cm in diameter was made on the back of each animal. Apart from routine disinfection, the Con rats were untreated, whereas the other two groups were treated with VG or MCD. On days 3, 7 and 14 post injury, the wound areas were observed and measured using image analysis software following photography, and the skin samples were harvested from wound tissue. Then, histopathological morphology was observed routinely by hematoxylin and eosin (HE) staining; tumor necrosis factor α (TNF-α) and interleukin (IL)-1ß expression were detected by Western blotting. Vascular endothelial growth factor (VEGF) and epidermal growth factor (EGF) expression were detected with immunohistochemistry. RESULTS: The MCD generated a sf electric potential greater than 0.95 V. Animal experiments showed that the wound-healing rate in the MCD group was significantly increased compared with the Con and VG groups (P < 0.05 or P < 0.01). Histopathological observation revealed an alleviated inflammatory response, induced vascular proliferation and accelerated epithelization in the MCD group. Moreover, samples from the MCD group expressed reduced TNF-α and IL-1ß levels and increased VEGF and EGF levels compared with those of the other two groups (P < 0.05 or P < 0.01). However, no significant difference was noted between the Con and VG groups at each time point. CONCLUSIONS: The MCD generates a stable and lasting ES and significantly promotes wound healing by reducing inflammation duration and increasing growth factors expression. Thus, MCD may act as a promising biomaterial device for skin wound healing.

Enhanced Neurite Outgrowth on a Multiblock Conductive Nerve Scaffold with Self-Powered Electrical Stimulation.

Electrical stimulation (ES) is widely applied to promote nerve regeneration. Currently, metal needles are used to exert external ES, which may cause pain and risk of infection. In this work, a multiblock conductive nerve scaffold with self-powered ES by the consumption of glucose and oxygen is prepared. The conductive substrate is prepared by in situ polymerization of polypyrrole (PPy) on the nanofibers of bacterial cellulose (BC). Platinum nanoparticles are electrodeposited on the anode side for glucose oxidation, while nitrogen-doped carbon nanotubes (N-CNTs) are loaded on the cathode side for oxygen reduction. The scaffold shows good mechanical property, flexibility and conductivity. The scaffold can form a potential difference of above 300 mV between the anode and the cathode in PBS with 5 × 10-3 m glucose. Dorsal root ganglions cultured on the Pt-BC/PPy-N-CNTs scaffold are 55% longer in mean neurite length than those cultured on BC/PPy. In addition, in vivo study indicates that the Pt-BC/PPy-N-CNTs scaffold promotes nerve regeneration compared with the BC/PPy group. This paper presents a novel design of a nerve scaffold with self-powered ES. In the future, it can be combined with other features to promote nerve regeneration.

Polyaniline Functionalized Graphene Nanoelectrodes for the Regeneration of PC12 Cells via Electrical Stimulation.

The regeneration of neurons is an important goal of neuroscience and clinical medicine. The electrical stimulation of cells is a promising technique to meet this goal. However, its efficiency highly depends on the electrochemical properties of the stimulation electrodes used. This work reports on the preparation and use of a highly electroactive and biocompatible nanoelectrode made from a novel polyaniline functionalized graphene composite. This nanocomposite was prepared using a facile and efficient polymerization-enhanced ball-milling method. It was used to stimulate the growth of PC12 cells under various electrical fields. The enhanced growth of axons and improved wound regeneration of PC12 cells were observed after this treatment, suggesting a promising strategy for neuro traumatology.

Brain Mesh: Technical Note.

BACKGROUND: Standard electrostimulation cortical mapping includes application of electrical current to the explored areas through an electrode and marking of functional zones by means of paper tags with different symbols. This approach has several disadvantages. First, the electrode is moved randomly. It leads to overlooking of some zones, which causes mapping deficiency, and restimulation of others, which can trigger epileptic seizures. Second, the tags easily shift and close the marked structures. We describe a new simple device that provides precise cortical mapping without indicated problems and the technique to apply it. METHODS: The device is a flexible polymer mesh with square pores of a certain size. The neurosurgeon applies the mesh onto the brain cortex and sequentially stimulates it through the pores. The functional areas are labeled. Pores corresponding to the lesion are cut out, and the lesion is removed through the cutout without removing the mesh. After operation, the mesh is removed. RESULTS: Using this technique, we operated on a patient with a glioma located near the primary motor cortex. The accessible cortical area was accurately mapped, and the tumor was resected without any complications. The mesh allowed us to significantly streamline the mapping process. CONCLUSIONS: Our case illustrates that the proposed invention can be successfully used in neurosurgical operations for precise electrostimulation mapping of the brain cortex.

Conductive electrospun scaffolds with electrical stimulation for neural differentiation of conjunctiva mesenchymal stem cells.

An electrical stimulus is a new approach to neural differentiation of stem cells. In this work, the neural differentiation of conjunctiva mesenchymal stem cells (CJMSCs) on a new 3D conductive fibrous scaffold of silk fibroin (SF) and reduced graphene oxide (rGo) were examined. rGo (3.5% w/w) was dispersed in SF-acid formic solution (10% w/v) and conductive nanofibrous scaffold was fabricated using the electrospinning method. SEM and TEM microscopies were used for fibrous scaffold characterization. CJMSCs were cultured on the scaffold and 2 electrical impulse models (Current 1:115 V/m, 100-Hz frequency and current 2:115 v/m voltages, 0.1-Hz frequency) were applied for 7 days. Also, the effect of the fibrous scaffold and electrical impulses on cell viability and neural gene expression were examined using MTT assay and qPCR analysis. Fibrous scaffold with the 220 ± 20 nm diameter and good dispersion of graphene nanosheets at the surface of nanofibers were fabricated. The MTT result showed the viability of cells on the scaffold, with current 2 lower than current 1. qPCR analysis confirmed that the expression of ß-tubulin (2.4-fold P ≤ 0.026), MAP-2 (1.48-fold; P ≤ 0.03), and nestin (1.5-fold; P ≤ 0.03) genes were higher in CJMSCs on conductive scaffold with 100-Hz frequency compared to 0.1-Hz frequency. Collectively, we proposed that SF-rGo fibrous scaffolds, as a new conductive fibrous scaffold with electrical stimulation are good strategies for neural differentiation of stem cells and the type of electrical pulses has an influence on neural differentiation and proliferation of CJMSCs.

Photoconductive Micro/Nanoscale Interfaces of a Semiconducting Polymer for Wireless Stimulation of Neuron-Like Cells.

We report multiscale structured fibers and patterned films based on a semiconducting polymer, poly(3-hexylthiophene) (P3HT), as photoconductive biointerfaces to promote neuronal stimulation upon light irradiation. The micro/nanoscale structures of P3HT used for neuronal interfacing and stimulation include nanofibers with an average diameter of 100 nm, microfibers with an average diameter of about 1 µm, and lithographically patterned stripes with width of 3, 25, and 50 µm, respectively. The photoconductive effect of P3HT upon light irradiation provides electrical stimulation for neuronal differentiation and directed growth. Our results demonstrate that neurons on P3HT nanofibers showed a significantly higher total number of branches, while neurons grown on P3HT microfibers had longer and thinner neurites. Such a combination strategy of topographical and photoconductive stimulation can be applied to further enhance neuronal differentiation and directed growth. These photoconductive polymeric micro/nanostructures demonstrated their great potential for neural engineering and development of novel neural regenerative devices.

An electroneurography-based assay for identifying injured nerve segment during surgery: design and in vivo application in the rat.

OBJECTIVE: Nerve injury is the main reason for nerve reconstruction surgery, during which the surgeon must determine the location of the injured nerve segment, resect it, and reconnect the remaining healthy nerve stump ends within a limited time. Given this importance, an assay needed to determine the exact location of the injured nerve segment, but no tool has yet fulfilled this need so that a visual inspection of the nerve is still the primary method of identifying the injured segment. APPROACH: We designed a flexible multi-electrode array sensor that records the electroneurographic signal (ENG) as the action potential elicited by electrical stimulation that propagates along the nerve upon both orthodromic and antidromic stimulation. Its utility was validated by in vivo experiments in injured sciatic nerves of rats. MAIN RESULTS: The results showed that the first post stimulus negative electroneurographic component (N1) is the most valid neural correlate, as its amplitude decreased, and latency increased as the action potential propagated across the injured segment. Gradual recovery of nerve conduction was observed when measured immediately, 7, and 30 d after injury. The locations of the identified injured segments were validated by histological findings. SIGNIFICANCE: The sensor and the algorithm developed in this study are breakthroughs in surgical nerve assessment accomplished by determining the specific nerve segment that should be resected, enabling the optimal surgical outcome.