Advances in applications of head mounted devices (HMDs): Physical techniques for drug delivery and neuromodulation.

Head-mounted medical devices (HMDs) are disruptive inventions representing laboratories and clinical institutions worldwide are climbing the apexes of brain science. These complex devices are inextricably linked with a wide range knowledge containing the Physics, Imaging, Biomedical engineering, Biology and Pharmacology, particularly could be specifically designed for individuals, and finally exerting integrated bio-effect. The salient characteristics of them are non-invasive intervening in human brain's physiological structures, and alterating the biological process, such as thermal ablating the tumor, opening the BBB to deliver drugs and neuromodulating to enhance cognitive performance or manipulate prosthetic. The increasing demand and universally accepted of them have set off a dramatic upsurge in HMDs' studies, seminal applications of them span from clinical use to psychiatric disorders and neurological modulation. With subsequent pre-clinical studies and human trials emerging, the mechanisms of transcranial stimulation methods of them were widely studied, and could be basically came down to three notable approach: magnetic, electrical and ultrasonic stimulation. This review provides a comprehensive overviews of their stimulating mechanisms, and recent advances in clinic and military. We described the potential impact of HMDs on brain science, and current challenges to extensively adopt them as promising alternative treating tools.

Self-Powered Electrical Impulse Chemotherapy for Oral Squamous Cell Carcinoma.

Oral squamous cell carcinoma (OSCC) is a common oral cancer of the head and neck, which causes tremendous physical and mental pain to people. Traditional chemotherapy usually results in drug resistance and side effects, affecting the therapy process. In this study, a self-powered electrical impulse chemotherapy (EIC) method based on a portable triboelectric nanogenerator (TENG) was established for OSCC therapy. A common chemotherapeutic drug, doxorubicin (DOX), was used in the experiment. The TENG designed with zigzag structure had a small size of 6 cm × 6 cm, which could controllably generate the fixed output of 200 V, 400 V and 600 V. The electrical impulses generated by the TENG increased the cell endocytosis of DOX remarkably. Besides, a simply and ingeniously designed microneedle electrode increased the intensity of electric field (EF) between two adjacent microneedle tips compared with the most used planar interdigital electrode at the same height, which was more suitable for three-dimensional (3D) cells or tissues. Based on the TENG, microneedle electrode and DOX, the self-powered EIC system demonstrated a maximal apoptotic cell ratio of 22.47% and a minimum relative 3D multicellular tumor sphere (MCTS) volume of 160% with the drug dosage of 1 µg mL-1.

Neurophysiological aspects of electrical pulse stimulation in patients with urolithiasis.

Stimulation of the peristaltic activity of the ureter is a pathogenetically substantiated component of the lithokinetic effect. AIM: The aim of the work was to study the effects of electrical impulse stimulation on ureteral motility in patients with urolithiasis. MATERIALS AND METHODS: 47 patients with urolithiasis, aged 27-59 years, with unilateral ureteral stones, up to 5 mm in size, were studied. The patients underwent translumbar electrical impulse stimulation according to the original method. The results were assessed by the change in the frequency of ureteral emissions and the duration of the interval between two consecutive ureteral emissions. RESULTS: As a result of the method used, there is an increase in the average frequency of ureteral ejections from 1.38±0.49 to 2.20±0.84 minutes (p<0.05), a decrease in the average duration of the interval between two consecutive ureteral ejections from 44.48 ±7 .89 to 27.96±3.89 seconds (p<0.05). The impact was well tolerated by patients. There were no changes in hemodynamic parameters. CONCLUSIONS: Transdermal exposure to single electric stimuli of a rectangular shape has significant effect in patients with urolithiasis as electric pulse stimulation helps to increase the peristaltic activity of the ureter by initiating additional peristaltic waves. To achieve this effect, it is advisable to apply range of 15-30 mA at a time moment corresponding to the last third of the interval between ureteral emissions, when applying stimulating electrodes in the lumbar region, in the area of the projection of the renal pelvis and the proximal ureter.

Types of Vascular Response to Direct Intraoperative Electrical Stimulation of the Sciatic Nerve after Autoneuroplasty and Their Effect on Limb Function Recovery.

We studied different types of the vascular response to direct intraoperative low-frequency electrical stimulation of the sciatic nerve after autoneuroplasty of its tibial portion and analyzed their effects on the limb function recovery. Rats (n=20) underwent 40-min intraoperative electrical stimulation, and hemodynamics in the leg was recorded by photoplethysmography. Functional recovery of the tibial nerve was assessed using a walking path analysis within 12 weeks after surgery. Three types of the vascular response to electrical stimulation were identified: the absence of pronounced hemodynamic changes during the electrostimulation session, hyperkinetic type of hemodynamics, and venous outflow disturbances. In rats demonstrating vascular responses of types I and II during the postoperative period, the functional index of the tibial nerve partially recovered within 12 weeks; in type III, no recovery was observed. It was concluded that the type of hemodynamics during intraoperative electrical stimulation of the damaged nerve subjected to autoneuroplasty affects further restoration of the motor function of the limb.

A conductive cell-delivery construct as a bioengineered patch that can improve electrical propagation and synchronize cardiomyocyte contraction for heart repair.

Cardiac tissue engineering is of particular importance in the combination of contracting cells with a biomaterial scaffold, which serves as a cell-delivery construct, to replace cardiomyocytes (CMs) that are lost as a result of an infarction, to restore heart function. However, most biomaterial scaffolds are nonconductive and may delay regional conduction, potentially causing arrhythmias. In this study, a conductive CM-delivery construct that consists of a gelatin-based gelfoam that is conjugated with a self-doped conductive polymer (poly-3-amino-4-methoxybenzoic acid, PAMB) is proposed as a cardiac patch (PAMB-Gel patch) to repair an infarcted heart. A nonconductive plain gelfoam (Gel patch) is used as a control. The electrical conductivity of the PAMB-Gel patch is approximately 30 times higher than that of the Gel patch; as a result, the conductive PAMB-Gel patch can substantially increase electrical conduction between distinct clusters of beating CMs, facilitating their synchronous contraction. In vivo epicardial implantation of the PAMB-Gel patch that is seeded with CMs (the bioengineered patch) in infarcted rat hearts can significantly enhance electrical activity in the fibrotic tissue, improving electrical impulse propagation and synchronizing CM contraction across the scar region, markedly reducing its susceptibility to cardiac arrhythmias. Echocardiography shows that the bioengineered conductive patch has an important role in the restoration of cardiac function, perhaps owing to the synergistic effects of its conductive construct and the synchronously beating CMs. These experimental results reveal that the as-proposed bioengineered conductive patch has great potential for repairing injured cardiac tissues.

A self-doping conductive polymer hydrogel that can restore electrical impulse propagation at myocardial infarct to prevent cardiac arrhythmia and preserve ventricular function.

Following myocardial infarction (MI), necrotic cardiomyocytes (CMs) are replaced by fibroblasts and collagen tissue, causing abnormal electrical signal propagation, desynchronizing cardiac contraction, resulting in cardiac arrhythmia. In this work, a conductive polymer, poly-3-amino-4-methoxybenzoic acid (PAMB), is synthesized and grafted onto non-conductive gelatin. The as-synthesized PAMB-G copolymer is self-doped in physiological pH environments, making it an electrically active material in biological tissues. This copolymer is cross-linked by carbodiimide to form an injectable conductive hydrogel (PAMB-G hydrogel). The un-grafted gelatin hydrogel is prepared in a similar manner as a control. Both test hydrogels not only provide an optimal matrix for CM adhesion and growth but also maintain CM morphology and functional proteins. The conductivity of PAMB-G hydrogel is ca. 12 times higher than that of gelatin hydrogel. Microelectrode array analyses reveal that a heart placed on the PAMB-G hydrogel has a higher field potential amplitude than that placed on the gelatin hydrogel and can pass current from one heart to excite another heart at a distance. The injection of PAMB-G hydrogel into the scar zone following an MI in a rat heart improves electrical impulse propagation over that in a heart that has been treated with gelatin hydrogel, and synchronizes heart contraction, leading to preservation of the ventricular function and reduction of cardiac arrhythmia, demonstrating its potential for use in treating MI.

A method to deliver patterned electrical impulses to Schwann cells cultured on an artificial axon.

Information from the brain travels back and forth along peripheral nerves in the form of electrical impulses generated by neurons and these impulses have repetitive patterns. Schwann cells in peripheral nerves receive molecular signals from axons to coordinate the process of myelination. There is evidence, however, that non-molecular signals play an important role in myelination in the form of patterned electrical impulses generated by neuronal activity. The role of patterned electrical impulses has been investigated in the literature using co-cultures of neurons and myelinating cells. The co-culturing method, however, prevents the uncoupling of the direct effect of patterned electrical impulses on myelinating cells from the indirect effect mediated by neurons. To uncouple these effects and focus on the direct response of Schwann cells, we developed an in vitro model where an electroconductive carbon fiber acts as an artificial axon. The fiber provides only the biophysical characteristics of an axon but does not contribute any molecular signaling. In our "suspended wire model", the carbon fiber is suspended in a liquid media supported by a 3D printed scaffold. Patterned electrical impulses are generated by an Arduino 101 microcontroller. In this study, we describe the technology needed to set-up and eventually replicate this model. We also report on our initial in vitro tests where we were able to document the adherence and ensheath of human Schwann cells to the carbon fiber in the presence of patterned electrical impulses (hSCs were purchased from ScienCell Research Laboratories, Carlsbad, CA, USA; ScienCell fulfills the ethic requirements, including donor's consent). This technology will likely make feasible to investigate the response of Schwann cells to patterned electrical impulses in the future.

Polypyrrole-chitosan conductive biomaterial synchronizes cardiomyocyte contraction and improves myocardial electrical impulse propagation.

Background: The post-myocardial infarction (MI) scar interrupts electrical impulse propagation and delays regional contraction, which contributes to ventricular dysfunction. We investigated the potential of an injectable conductive biomaterial to restore scar tissue conductivity and re-establish synchronous ventricular contraction. Methods: A conductive biomaterial was generated by conjugating conductive polypyrrole (PPY) onto chitosan (CHI) backbones. Trypan blue staining of neonatal rat cardiomyocytes (CMs) cultured on biomaterials was used to evaluate the biocompatibility of the conductive biomaterials. Ca2+ imaging was used to visualize beating CMs. A cryoablation injury rat model was used to investigate the ability of PPY:CHI to improve cardiac electrical propagation in the injured heart in vivo. Electromyography was used to evaluate conductivity of scar tissue ex vivo. Results: Cell survival and morphology were similar between cells cultured on biomaterials-coated and uncoated-control dishes. PPY:CHI established synchronous contraction of two distinct clusters of spontaneously-beating CMs. Intramyocardial PPY:CHI injection into the cryoablation-induced injured region improved electrical impulse propagation across the scarred tissue and decreased the QRS interval, whereas saline- or CHI-injected hearts continued to have delayed propagation patterns and significantly reduced conduction velocity compared to healthy controls. Ex vivo evaluation found that scar tissue from PPY:CHI-treated rat hearts had higher signal amplitude compared to those from saline- or CHI-treated rat heart tissue. Conclusions: The PPY:CHI biomaterial is electrically conductive, biocompatible and injectable. It improved synchronous contraction between physically separated beating CM clusters in vitro. Intra-myocardial injection of PPY:CHI following cardiac injury improved electrical impulse propagation of scar tissue in vivo.

16-Channel Flexible System to Measure Electrophysiological Properties of Bioengineered Hearts.

As tissue engineering continues to mature, it is necessary to develop new technologies that bring insight into current paradigms and guide improvements for future experiments. To this end, we have developed a system to characterize our bioartificial heart model and compare them to functional native structures. In the present study, the hearts of adult Sprague-Dawley were decellularized resulting in a natural three-dimensional cardiac scaffold. Neonatal rat primary cardiac cells were then cultured within a complex 3D fibrin gel, forming a 3-dimensional cardiac construct, which was sutured to the acellular scaffold and suspended in media for 24-48 h. The resulting bioartificial hearts (BAHs) were then affixed with 16 electrodes, in different configurations to evaluate not only the electrocardiographic characteristics of the cultured tissues, but to also test the system's consistency. Histological evaluation showed cellularization and cardiac tissue formation. The BAHs and native hearts were then evaluated with our 16-channel flexible system to acquire the metrics associated with their respective electrophysiological properties. Time delays between the native signals were in the range of 0-95 ms. As well, color maps revealed a trend in impulse propagation throughout the native hearts. After evaluation of the normal rat QRS complex we found the average amplitude of the R-wave to be 5351.48 ± 44.92 µV and the average QRS duration was found to be 10.61 ± 0.18 ms. In contrast, BAHs exhibited more erratic and non-uniform activity that garnered no appreciable quantification. The data collected in this study proves our system's efficacy for EKG data procurement.

Enhanced Cardiac Differentiation of Human Cardiovascular Disease Patient-Specific Induced Pluripotent Stem Cells by Applying Unidirectional Electrical Pulses Using Aligned Electroactive Nanofibrous Scaffolds.

In the embryonic heart, electrical impulses propagate in a unidirectional manner from the sinus venosus and appear to be involved in cardiogenesis. In this work, aligned and random polyaniline/polyetersulfone (PANI/PES) nanofibrous scaffolds doped by Camphor-10-sulfonic acid (ß) (CPSA) were fabricated via electrospinning and used to conduct electrical impulses in a unidirectional and multidirectional fashion, respectively. A bioreactor was subsequently engineered to apply electrical impulses to cells cultured on PANI/PES scaffolds. We established cardiovascular disease-specific induced pluripotent stem cells (CVD-iPSCs) from the fibroblasts of patients undergoing cardiothoracic surgeries. The CVD-iPSCs were seeded onto the scaffolds, cultured in cardiomyocyte-inducing factors, and exposed to electrical impulses for 1 h/day, over a 15-day time period in the bioreactor. The application of the unidirectional electrical stimulation to the cells significantly increased the number of cardiac Troponin T (cTnT+) cells in comparison to multidirectional electrical stimulation using random fibrous scaffolds. This was confirmed by real-time polymerase chain reaction for cardiac-related transcription factors (NKX2.5, GATA4, and NPPA) and a cardiac-specific structural gene (TNNT2). Here we report for the first time that applying electrical pulses in a unidirectional manner mimicking the unidirectional wave of electrical stimulation in the heart, could increase the derivation of cardiomyocytes from CVD-iPSCs.

Estudo comparativo da eletrocardiografia convencional e computadorizada em equinos das raças Quarto de Milha e Mangalarga Marchador / Comparative study of computerized and conventional electrocardiography in Quarter Horse and Mangalarga Marchador

A eletrocardiografia computadorizada é mais precisa e prática quando comparada à convencional e por essa razão vem ganhando espaço na rotina clínica. No entanto os valores de referência devem diferir para os dois métodos. O objetivo desse trabalho foi analisar e comparar o exame eletrocardiográfico computadorizado com o exame obtido pelo método convencional em equinos. O estudo demonstrou diferenças na amplitude da onda P (P<0,0001) com valor médio de 0,21 mV para o método convencional e 0,17 mV para o computadorizado; duração do intervalo PR (p=0,0005), tendo o valor médio de 260,49 ms para o método convencional e 242,37 ms para o informatizado e duração do complexo QRS (p=0,0003), sendo a média de valores para o método convencional de 75,61ms e 84,83 ms para o computadorizado. Essas diferenças devem ser levadas em consideração com o intuito de evitar equívocos na interpretação da eletrocardiografia na espécie equina.

Computerized electrocardiography has been gaining space in clinic routines because it is more practical and precise when compared to the conventional method. However, their reference values may differ from each other. The aim of this paper was to analyze and compare computerized and conventional electrocardiography in horses. Differences were observed between P wave amplitude (P<0001) with a mean of 0.21mV in the conventional method and 0.17mV in the computerized method, PR interval duration (p=0.0005) with a mean of 260.49 ms and 242.37 ms in the conventional and computerized methods respectively, and QRS complex duration (p=0.0003) with a mean of 75.61 ms in the conventional method and 84.83 ms in the computerized method. These differences should be taken into consideration in order to avoid misunderstandings in the interpretation of the electrocardiogram in equine species.

Macroscopic electrical propagation in the guinea pig urinary bladder.

There is little knowledge about macroscopic electrical propagation in the wall of the urinary bladder. Recording simultaneously from a large number of extracellular electrodes is one technology that could be used to study the patterns of macroscopic electrical propagations. The urinary bladders from 14 guinea pigs were isolated and placed in an organ bath. A 16 × 4-electrode array was positioned at various sites on the serosal bladder surface, and recordings were performed at different intravesical volumes. In four experiments, carbachol (CCH; 10(-6) M), nifedipine (10 mM), or tetrodotoxin (TTX; 10(-6) M) was added to the superfusing fluid. After the experiments, the extracellular signals were analyzed and propagation maps were constructed. Electrical waves were detected at all sites on the bladder surface and propagated for a limited distance before terminating spontaneously. The majority of waves (>90%) propagated in the axial direction (i.e., from dome to base or vice versa). An increase in vesicle volume significantly decreased the conduction velocity (from 4.9 ± 1.5 to 2.7 ± 0.7 cm/s; P < 0.05). CCH increased, nifedipine decreased, while TTX had little effect on electrical activities. In addition, a new electrical phenomenon, termed a "patch," was discovered whereby a simultaneous electrical deflection was detected across an area of the bladder surface. Two types of electrical activities were detected on the bladder surface: 1) electrical waves propagating preferentially in the axial direction and 2) electrical patches. The propagating electrical waves could form the basis for local spontaneous contractions in the bladder during the filling phase.