Filtration-processed biomass nanofiber electrodes for flexible bioelectronics.

An increasing demand for bioelectronics that interface with living systems has driven the development of materials to resolve mismatches between electronic devices and biological tissues. So far, a variety of different polymers have been used as substrates for bioelectronics. Especially, biopolymers have been investigated as next-generation materials for bioelectronics because they possess interesting characteristics such as high biocompatibility, biodegradability, and sustainability. However, their range of applications has been restricted due to the limited compatibility of classical fabrication methods with such biopolymers. Here, we introduce a fabrication process for thin and large-area films of chitosan nanofibers (CSNFs) integrated with conductive materials. To this end, we pattern carbon nanotubes (CNTs), silver nanowires, and poly (3,4-ethylenedioxythiophene):poly (styrenesulfonate) (PEDOT:PSS) by a facile filtration process that uses polyimide masks fabricated via laser ablation. This method yields feedlines of conductive material on nanofiber paper and demonstrates compatibility with conjugated and high-aspect-ratio materials. Furthermore, we fabricate a CNT neural interface electrode by taking advantage of this fabrication process and demonstrate peripheral nerve stimulation to the rapid extensor nerve of a live locust. The presented method might pave the way for future bioelectronic devices based on biopolymer nanofibers.

Translation of an existing implantable cardiac monitoring device for measurement of gastric electrical slow-wave activity.

BACKGROUND: Despite evidence that slow-wave dysrhythmia in the stomach is associated with clinical conditions such as gastroparesis and functional dyspepsia, there is still no widely available device for long-term monitoring of gastric electrical signals. Actionable biomarkers of gastrointestinal health are critically needed, and an implantable slow-wave monitoring device could aid in the establishment of causal relationships between symptoms and gastric electrophysiology. Recent developments in the area of wireless implantable gastric monitors demonstrate potential, but additional work and validation are required before this potential can be realized. METHODS: We hypothesized that translating an existing implantable cardiac monitoring device, the Reveal LINQ™ (Medtronic), would present a more immediate solution. Following ethical approval and laparotomy in anesthetized pigs (n = 7), a Reveal LINQ was placed on the serosal surface of the stomach, immediately adjacent to a validated flexible-printed-circuit (FPC) electrical mapping array. Data were recorded for periods of 7.5 min, and the resultant signal characteristics from the FPC array and Reveal LINQ were compared. KEY RESULTS: The Reveal LINQ device recorded slow waves in 6/7 subjects with a comparable period (p = 0.69), signal-to-noise ratio (p = 0.58), and downstroke width (p = 0.98) to the FPC, but with reduced amplitude (p = 0.024). Qualitatively, the Reveal LINQ slow-wave signal lacked the prolonged repolarization phase present in the FPC signals. CONCLUSIONS & INFERENCES: These findings suggest that existing cardiac monitors may offer an efficient solution for the long-term monitoring of slow waves. Translation toward implantation now awaits.

Annular Conductive Hydrogel-Mediated Wireless Electrical Stimulation for Augmenting Neurogenesis.

Electrical stimulation (ES) has a remarkable capacity to regulate neuronal differentiation and neurogenesis in the treatment of various neurological diseases. However, wired devices connected to the stimulating electrode and the mechanical mismatch between conventional rigid electrodes and soft tissues restrict their motion and cause possible infections, thereby limiting their clinical utility. An approach integrating the advantages of wireless techniques and soft hydrogels provides new insights into ES-induced nerve regeneration. Herein, a flexible and implantable wireless ES-responsive electrode based on an annular gelatin methacrylate-polyaniline (Gel/Pani) hydrogel is fabricated and used as a secondary coil to achieve wireless ES via electromagnetic induction in the presence of a primary coil. The Gel/Pani hydrogels exhibit favorable biocompatibility, biodegradability, conductivity, and compression resistance. The annular electrode of the Gel/Pani conductive hydrogel (AECH) supports neural stem cell growth, while the applied wireless ES facilitates neuronal differentiation and the formation of functional neural networks in vitro. Furthermore, AECH is implanted in vivo in rats with ischemic stroke and the results reveal that AECH-mediated wireless ES significantly ameliorates brain impairment and neurological function by activating endogenous neurogenesis. This novel flexible hydrogel system addresses wireless stimulation and implantable technical challenges, holding great potential for the treatment of neurodegenerative diseases.

[History of the implantable cardioverter-defibrillator in Germany]. / Die Geschichte des implantierbaren Kardioverter-Defibrillators in Deutschland.

The implantable cardioverter-defibrillator (ICD) was a breakthrough in the prevention of sudden cardiac death. After years of technical development in the USA, Michel Mirowski succeeded in proving reliable automatic defibrillation of ventricular tachyarrhythmias through initial human implantations in 1980, despite many obstacles. Nearly 4 years later, the first patients received ICDs at multiple centers in Germany. Subsequently, outside the USA, Germany became the country with highest implantation rates. The absolute number of implantations remained small as long as implantations required epicardial defibrillation electrodes and therefore thoracotomy by cardiac surgeons. Pacemaker-like implantation using a transvenous defibrillation electrode with a pectoral ICD became feasible in the early 1990s pushing implantation rates to the next level. Technical advancements were accompanied by clinical research in Germany, and often, the first-in-human studies were conducted in Germany. In 1991, the first guidelines for indications were established in the USA and Germany. Several randomized studies on indications were published between 1996 and 2009, mostly led by American teams with German participation, but also under German leadership (CASH, CAT, DINAMIT, IRIS). The DANISH study in 2016 questioned the results of these long-standing studies. Instead of providing ICDs to patients using a broad indication, future efforts aim to identify patients who, despite optimal medical therapy, cardiac resynchronization therapy (CRT), and/or catheter ablation, need protection against sudden cardiac death. Risk scores incorporating myocardial scars in magnetic resonance imaging (MRI) and genetic information are expected to contribute to more individualized and effective indications.

Stability of Ti3C2Tx MXene Films and Devices under Clinical Sterilization Processes.

MXenes are being heavily investigated in biomedical research, with applications ranging from regenerative medicine to bioelectronics. To enable the adoption and integration of MXenes into therapeutic platforms and devices, however, their stability under standard sterilization procedures must be established. Here, we present a comprehensive investigation of the electrical, chemical, structural, and mechanical effects of common thermal (autoclave) and chemical (ethylene oxide (EtO) and H2O2 gas plasma) sterilization protocols on both thin-film Ti3C2Tx MXene microelectrodes and mesoscale arrays made from Ti3C2Tx-infused cellulose-elastomer composites. We also evaluate the effectiveness of the sterilization processes in eliminating all pathogens from the Ti3C2Tx films and composites. Post-sterilization analysis revealed that autoclave and EtO did not alter the DC conductivity, electrochemical impedance, surface morphology, or crystallographic structure of Ti3C2Tx and were both effective at eliminating E. coli from both types of Ti3C2Tx-based devices. On the other end, exposure to H2O2 gas plasma sterilization for 45 min induced severe degradation of the structure and properties of Ti3C2Tx films and composites. The stability of the Ti3C2Tx after EtO and autoclave sterilization and the complete removal of pathogens establish the viability of both sterilization processes for Ti3C2Tx-based technologies.

BIMMS: A versatile and portable system for biological tissue and electrode-tissue interface electrical characterization.

The presented design is a low-cost, compact, and open-source USB-controlled platform for biological tissue and electrode-tissue interface electrical measurements, capable of potentiostatic and galvanostatic electrical impedance spectroscopy up to 10 MHz and cyclic voltammetry with voltage compliance of +-8 V and up to 2.4 mA while ensuring tissue-safety conditions. The data acquisition and generation are based on an Analog Discovery 2 platform (Digilent, USA). We provide accuracy analysis and comparisons with a commercially available calibrated impedance analyzer. Impedance measurements are demonstrated on implanted electrodes for neural stimulation and on an isolated ex-vivo calf brain as an example use case of the presented design.

Neurostimulation artifact removal for implantable sensors improves signal clarity and decoding of motor volition.

As the demand for prosthetic limbs with reliable and multi-functional control increases, recent advances in myoelectric pattern recognition and implanted sensors have proven considerably advantageous. Additionally, sensory feedback from the prosthesis can be achieved via stimulation of the residual nerves, enabling closed-loop control over the prosthesis. However, this stimulation can cause interfering artifacts in the electromyographic (EMG) signals which deteriorate the reliability and function of the prosthesis. Here, we implement two real-time stimulation artifact removal algorithms, Template Subtraction (TS) and ε-Normalized Least Mean Squares (ε-NLMS), and investigate their performance in offline and real-time myoelectric pattern recognition in two transhumeral amputees implanted with nerve cuff and EMG electrodes. We show that both algorithms are capable of significantly improving signal-to-noise ratio (SNR) and offline pattern recognition accuracy of artifact-corrupted EMG signals. Furthermore, both algorithms improved real-time decoding of motor intention during active neurostimulation. Although these outcomes are dependent on the user-specific sensor locations and neurostimulation settings, they nonetheless represent progress toward bi-directional neuromusculoskeletal prostheses capable of multifunction control and simultaneous sensory feedback.

Restoring Hand Functions in People with Tetraplegia through Multi-Contact, Fascicular, and Auto-Pilot Stimulation: A Proof-of-Concept Demonstration.

Two multi-contact epineural electrodes were placed around radial and median nerves of two subjects with high tetraplegia C4, American Spinal Injury Association Impairment Scale (AIS) A, group 0 of the International Classification for Surgery of the Hand in Tetraplegia. The purpose was to study the safety and capability of these electrodes to generate synergistic motor activation and functional movements and to test control interfaces that allow subjects to trigger pre-programmed stimulation sequences. The device consists of a pair of neural cuff electrodes and percutaneous cables with two extracorporeal connection cables inserted during a surgical procedure and maintained for 28 days. Continuity tests of the electrodes, selectivity of movements induced, motor capacities for grasping and gripping, conformity of the control order, tolerance, and acceptability were assessed. Neither of the two participants showed general and local comorbidity. Acceptability was optimal. None of the stimulation configurations generated contradictory movements. The success rate in task execution by the electro-stimulated hand exceeded the target of 50% (54% and 51% for patients 1 and 2, respectively). The compliance rate of the control orders in both patients was >90% using motion inertial measurement unit (IMU)-based detection and 100% using electromyography (EMG)-based detection in patient 1. These results support the relevance of neural stimulation of the tetraplegic upper limb with a more selective approach, using multi-contact epineural electrodes with nine and six contact points for the median and radial nerve respectively.

A Stretchable and Transparent Electrode Based on PEGylated Silk Fibroin for In Vivo Dual-Modal Neural-Vascular Activity Probing.

Transparent electrodes that form seamless contact and enable optical interrogation at the electrode-brain interface are potentially of high significance for neuroscience studies. Silk hydrogels can offer an ideal platform for transparent neural interfaces owing to their superior biocompatibility. However, conventional silk hydrogels are too weak and have difficulties integrating with highly conductive and stretchable electronics. Here, a transparent and stretchable hydrogel electrode based on poly(3,4-ethylenedioxythiophene):polystyrene sulfonate (PEDOT:PSS) and PEGylated silk protein is reported. PEGylated silk protein with poly(ethylene glycol) diglycidyl ether (PEGDE) improves the Young's modulus to 1.51-10.73 MPa and the stretchability to ≈400% from conventional silk hydrogels (<10 kPa). The PEGylated silk also helps form a robust interface with PEDOT:PSS thin film, making the hydrogel electrode synergistically incorporate superior stretchability (≈260%), stable electrical performance (≈4 months), and a low sheet resistance (≈160 ± 56 Ω sq-1 ). Finally, the electrode facilitates efficient electrical recording, and stimulation with unobstructed optical interrogation and rat-brain imaging are demonstrated. The highly transparent and stretchable hydrogel electrode offers a practical tool for neuroscience and paves the way for a harmonized tissue-electrode interface.

Graphene-Based Electrode Materials for Neural Activity Detection.

The neural electrode technique is a powerful tool for monitoring and regulating neural activity, which has a wide range of applications in basic neuroscience and the treatment of neurological diseases. Constructing a high-performance electrode-nerve interface is required for the long-term stable detection of neural signals by electrodes. However, conventional neural electrodes are mainly fabricated from rigid materials that do not match the mechanical properties of soft neural tissues, thus limiting the high-quality recording of neuroelectric signals. Meanwhile, graphene-based nanomaterials can form stable electrode-nerve interfaces due to their high conductivity, excellent flexibility, and biocompatibility. In this literature review, we describe various graphene-based electrodes and their potential application in neural activity detection. We also discuss the biological safety of graphene neural electrodes, related challenges, and their prospects.

Merging brain-computer interface and functional electrical stimulation technologies for movement restoration.

BCI (brain-computer interface) and functional electrical stimulation (FES) technologies have advanced significantly over the last several decades. Recent efforts have involved the integration of these technologies with the goal of restoring functional movement in paralyzed patients. Implantable BCIs have provided neural recordings with increased spatial resolution and have been combined with sophisticated neural decoding algorithms and increasingly capable FES systems to advance efforts toward this goal. This chapter reviews historical developments that have occurred as the exciting fields of BCI and FES have evolved and now overlapped to allow new breakthroughs in medicine, targeting restoration of movement and lost function in users with disabilities.

Diamond/Porous Titanium Nitride Electrodes With Superior Electrochemical Performance for Neural Interfacing.

Robust devices for chronic neural stimulation demand electrode materials which exhibit high charge injection (Q inj) capacity and long-term stability. Boron-doped diamond (BDD) electrodes have shown promise for neural stimulation applications, but their practical applications remain limited due to the poor charge transfer capability of diamond. In this work, we present an attractive approach to produce BDD electrodes with exceptionally high surface area using porous titanium nitride (TiN) as interlayer template. The TiN deposition parameters were systematically varied to fabricate a range of porous electrodes, which were subsequently coated by a BDD thin-film. The electrodes were investigated by surface analysis methods and electrochemical techniques before and after BDD deposition. Cyclic voltammetry (CV) measurements showed a wide potential window in saline solution (between -1.3 and 1.2 V vs. Ag/AgCl). Electrodes with the highest thickness and porosity exhibited the lowest impedance magnitude and a charge storage capacity (CSC) of 253 mC/cm2, which largely exceeds the values previously reported for porous BDD electrodes. Electrodes with relatively thinner and less porous coatings displayed the highest pulsing capacitances (C pulse), which would be more favorable for stimulation applications. Although BDD/TiN electrodes displayed a higher impedance magnitude and a lower C pulse as compared to the bare TiN electrodes, the wider potential window likely allows for higher Q inj without reaching unsafe potentials. The remarkable reduction in the impedance and improvement in the charge transfer capacity, together with the known properties of BDD films, makes this type of coating as an ideal candidate for development of reliable devices for chronic neural interfacing.

Biomimetic Intraneural Sensory Feedback Enhances Sensation Naturalness, Tactile Sensitivity, and Manual Dexterity in a Bidirectional Prosthesis.

Peripheral intraneural stimulation can provide tactile information to amputees. However, efforts are still necessary to identify encoding strategy eliciting percepts that are felt as both natural and effective for prosthesis control. Here we compared the naturalness and efficacy of different encoding strategies to deliver neural stimulation to trans-radial amputees implanted with intraneural electrodes. Biomimetic frequency modulation was perceived as more natural, while amplitude modulation enabled better performance in tasks requiring fine identification of the applied force. Notably, the optimal combination of naturalness and sensitivity of the tactile feedback can be achieved with "hybrid" encoding strategies based on simultaneous biomimetic frequency and amplitude neuromodulation. These strategies improved the gross manual dexterity of the subjects during functional task while maintaining high levels of manual accuracy. They also improved prosthesis embodiment, reducing abnormal phantom limb perceptions ("telescoping effect"). Hybrid strategies are able to provide highly sensitive and natural percepts and should be preferred. VIDEO ABSTRACT.

Remoção Percutânea de Eletrodos de Estimulação Cardíaca Artificial em um Único Centro Sul-Americano / Percutaneous Removal of Cardiac Leads in a Single Center in South America

Resumo Fundamento: Nas últimas décadas, o número de dispositivos eletrônicos cardíacos implantáveis (DCEI) aumentou consideravelmente, assim como a necessidade de remoção destes. Neste contexto, a remoção percutânea apresenta-se como uma técnica segura e capaz de evitar uma cirurgia cardíaca convencional. Objetivos: Primário: descrever a taxa de sucesso e complicações da remoção percutânea de DCEI em um hospital público brasileiro. Secundário: estabelecer preditores de sucesso e complicações. Métodos: Serie de casos retrospectiva de todos os pacientes submetidos à remoção de DCEI em um hospital público brasileiro no período de janeiro de 2013 a junho de 2018. Remoção, explante e extração de eletrodos, complicações e desfechos foram definidos conforme a diretriz norte-americana de 2017. Variáveis categóricas foram comparadas pelos testes Qui-quadrado ou Fisher, enquanto variáveis contínuas, por testes não pareados. O nível de significância adotado nas análises estatísticas foi de 5%. Resultados: 61 pacientes foram submetidos à remoção de DCEI, sendo 51 extrações e 10 explantes. No total, 128 eletrodos foram removidos. Taxa de sucesso clínico foi 100% no grupo do explante e 90,2% no da extração (p=0,58). Complicações maiores foram encontradas em 6,6% dos pacientes. Falha do procedimento foi associada a eletrodos de ventrículo (p=0,05) e átrio (p=0,04) direito implantados há mais tempo. Duração do procedimento (p=0,003) e necessidade de transfusão sanguínea (p<0,001) foram associadas a maior índice de complicação. Conclusão: As taxas de complicação e sucesso clínico observadas foram de 11,5% e 91,8%, respectivamente. Remoções de eletrodos atriais e ventriculares mais antigos estiveram associados a menores taxa de sucesso. Procedimentos mais longos e necessidade de transfusão sanguínea foram associados a complicações.

Abstract Background: In the last decade, the number of cardiac electronic devices has risen considerably and consequently the occasional need for their removal. Concurrently, the transvenous lead removal became a safe procedure that could prevent open-heart surgery. Objective: The primary objective of this study was to describe the successful performance and the complication rates of pacemaker removals in a Brazilian public hospital. Our secondary aim was to describe the variables associated to successes and complications. Methods: A retrospective case series was conducted in patients submitted to pacemaker removal in a Brazilian public hospital from January 2013 to June 2018. Removal, explant, extraction, success and complication rates were defined by the 2017 Heart Rhythm Society Guideline. Categorical variables were compared using x2 or Fisher's tests, while continuous variables were compared by unpaired tests. A p-value of 0.05 was considered statistically significant. Results: Cardiac device removals were performed in 61 patients, of which 51 were submitted to lead extractions and 10 to lead explants. In total, 128 leads were removed. Our clinical success rate was 100% in the explant group and 90.2% in the extraction one (p=0.58). Major complications were observed in 6.6% patients. Procedure failure was associated to older right ventricle (p=0.05) and atrial leads (p=0,04). Procedure duration (p=0.003) and need for blood transfusion (p<0,001) were associated to more complications. Conclusion: Complications and clinical success were observed in 11.5% and 91.8% of the population, respectively. Removal of older atrial and ventricular leads were associated with lower success rates. Longer procedures and blood transfusions were associated with complications.

First-in-man demonstration of a fully implanted myoelectric sensors system to control an advanced electromechanical prosthetic hand.

BACKGROUND: Advanced motorized prosthetic devices are currently controlled by EMG signals generated by residual muscles and recorded by surface electrodes on the skin. These surface recordings are often inconsistent and unreliable, leading to high prosthetic abandonment rates for individuals with upper limb amputation. Surface electrodes are limited because of poor skin contact, socket rotation, residual limb sweating, and their ability to only record signals from superficial muscles, whose function frequently does not relate to the intended prosthetic function. More sophisticated prosthetic devices require a stable and reliable interface between the user and robotic hand to improve upper limb prosthetic function. NEW METHOD: Implantable Myoelectric Sensors (IMES(®)) are small electrodes intended to detect and wirelessly transmit EMG signals to an electromechanical prosthetic hand via an electro-magnetic coil built into the prosthetic socket. This system is designed to simultaneously capture EMG signals from multiple residual limb muscles, allowing the natural control of multiple degrees of freedom simultaneously. RESULTS: We report the status of the first FDA-approved clinical trial of the IMES(®) System. This study is currently in progress, limiting reporting to only preliminary results. COMPARISON WITH EXISTING METHODS: Our first subject has reported the ability to accomplish a greater variety and complexity of tasks in his everyday life compared to what could be achieved with his previous myoelectric prosthesis. CONCLUSION: The interim results of this study indicate the feasibility of utilizing IMES(®) technology to reliably sense and wirelessly transmit EMG signals from residual muscles to intuitively control a three degree-of-freedom prosthetic arm.