Advancing Cardiomyocyte Maturation: Current Strategies and Promising Conductive Polymer-Based Approaches.

Cardiovascular diseases are a leading cause of mortality and pose a significant burden on healthcare systems worldwide. Despite remarkable progress in medical research, the development of effective cardiovascular drugs has been hindered by high failure rates and escalating costs. One contributing factor is the limited availability of mature cardiomyocytes (CMs) for accurate disease modeling and drug screening. Human induced pluripotent stem cell-derived CMs offer a promising source of CMs; however, their immature phenotype presents challenges in translational applications. This review focuses on the road to achieving mature CMs by summarizing the major differences between immature and mature CMs, discussing the importance of adult-like CMs for drug discovery, highlighting the limitations of current strategies, and exploring potential solutions using electro-mechano active polymer-based scaffolds based on conductive polymers. However, critical considerations such as the trade-off between 3D systems and nutrient exchange, biocompatibility, degradation, cell adhesion, longevity, and integration into wider systems must be carefully evaluated. Continued advancements in these areas will contribute to a better understanding of cardiac diseases, improved drug discovery, and the development of personalized treatment strategies for patients with cardiovascular disorders.

Highly Stable Low-Strain Flexible Sensors Based on Gold Nanoparticles/Silica Nanohelices.

Flexible strain sensors based on nanoparticle (NP) arrays show great potential for future applications such as electronic skin, flexible touchscreens, healthcare sensors, and robotics. However, even though these sensors can exhibit high sensitivity, they are usually not very stable under mechanical cycling and often exhibit large hysteresis, making them unsuitable for practical applications. In this work, strain sensors based on silica nanohelix (NH) arrays grafted with gold nanoparticles (AuNPs) can overcome these critical aspects. These 10 nm AuNPs are functionalized with mercaptopropionic acid (MPA) and different ratios of thiol-polyethylene glycol-carboxylic acid (HS-PEG7-COOH) to optimize the colloidal stability of the resulting NH@AuNPs nanocomposite suspensions, control their aggregation state, and tune the thickness of the insulating layer. They are then grafted covalently onto the surface of the NHs by chemical coupling. These nanomaterials exhibit a well-defined arrangement of AuNPs, which follows the helicity of the silica template. The modified NHs are then aligned by dielectrophoresis (DEP) between interdigitated electrodes on a flexible substrate. The flexibility, stability, and especially sensitivity of these sensors are then characterized by electromechanical measurements and scanning electron microscopy observations. These strain sensors based on NH@AuNPs nanocomposites are much more stable than those containing only nanoparticles and exhibit significantly reduced hysteresis and high sensitivity at very slight strains. They can retain their sensitivity even after 2 million consecutive cycles with virtually unchanged responsiveness. These improved performances come from their mechanical stability and the use of nanohelices as stable mechanical templates.

Hollow ring-like flexible electrode architecture enabling subcellular multi-directional neural interfacing.

Implantable neural microelectrodes for recording and stimulating neural activity are critical for research in neuroscience and clinical neuroprosthetic applications. A current need exists for developing new technological solutions for obtaining highly selective and stealthy electrodes that provide reliable neural integration and maintain neuronal viability. This paper reports a novel Hollow Ring-like type electrode to sense and/or stimulate neural activity from three-dimensional neural networks. Due to its unique design, the ring electrode architecture enables easy and reliable access of the electrode to three-dimensional neural networks with reduced mechanical contact on the biological tissue, while providing improved electrical interface with cells. The Hollow Ring electrodes, particularly when coated with the conducting polymer poly(3,4-ethylenedioxythiophene) polystyrene sulfonate (PEDOT:PSS), show improved electrical properties with extremely low impedance (7 MΩ µm2) and high charge injection capabilities (15 mC/cm2), when compared to traditional planar disk-type electrodes. The ring design also serves as an optimal architecture for cell growth to create an optimal subcellular electrical-neural interface. In addition, we showed that neural signals recorded by the ring electrode were better resolved than recordings from a traditional disk-type electrode improving the signal-to-noise ratio (SNR) and the burst detection from 3D neuronal networks in vitro. Overall, our results suggest the great potential of the hollow ring design for developing next-generation microelectrodes for applications in neural interfaces used in physiological studies and neuromodulation applications.

Scalable batch fabrication of ultrathin flexible neural probes using a bioresorbable silk layer.

Flexible intracerebral probes for neural recording and electrical stimulation have been the focus of many research works to achieve better compliance with the surrounding tissue while minimizing rejection. Strategies have been explored to find the best way to insert flexible probes into the brain while maintaining their flexibility once positioned. Here, we present a novel and versatile scalable batch fabrication approach to deliver ultrathin and flexible probes consisting of a silk-parylene bilayer. The biodegradable silk layer, whose degradation time is programmable, provides a temporary and programmable stiffener to allow the insertion of ultrathin parylene-based flexible devices. Our innovative and robust batch fabrication technology allows complete freedom over probe design in terms of materials, size, shape, and thickness. We demonstrate successful ex vivo insertion of the probe with acute high-fidelity recordings of epileptic seizures in field potentials as well as single-unit action potentials in mouse brain slices. Our novel technological solution for implanting ultraflexible devices in the brain while minimizing rejection risks shows high potential for use in both brain research and clinical therapies.

Nanofibrous PEDOT-Carbon Composite on Flexible Probes for Soft Neural Interfacing.

In this study, we report a flexible implantable 4-channel microelectrode probe coated with highly porous and robust nanocomposite of poly (3,4-ethylenedioxythiophene) (PEDOT) and carbon nanofiber (CNF) as a solid doping template for high-performance in vivo neuronal recording and stimulation. A simple yet well-controlled deposition strategy was developed via in situ electrochemical polymerization technique to create a porous network of PEDOT and CNFs on a flexible 4-channel gold microelectrode probe. Different morphological and electrochemical characterizations showed that they exhibit remarkable and superior electrochemical properties, yielding microelectrodes combining high surface area, low impedance (16.8 ± 2 MΩ µm2 at 1 kHz) and elevated charge injection capabilities (7.6 ± 1.3 mC/cm2) that exceed those of pure and composite PEDOT layers. In addition, the PEDOT-CNF composite electrode exhibited extended biphasic charge cycle endurance and excellent performance under accelerated lifetime testing, resulting in a negligible physical delamination and/or degradation for long periods of electrical stimulation. In vitro testing on mouse brain slices showed that they can record spontaneous oscillatory field potentials as well as single-unit action potentials and allow to safely deliver electrical stimulation for evoking field potentials. The combined superior electrical properties, durability and 3D microstructure topology of the PEDOT-CNF composite electrodes demonstrate outstanding potential for developing future neural surface interfacing applications.

Microelectrodes from PEDOT-carbon nanofiber composite for high performance neural recording, stimulation and neurochemical sensing.

This present method describes a versatile approach for the electrochemical synthesis of a composite material of Poly (3,4-ethylenedioxythiophene) (PEDOT) and Carbon Nanofibers (CNFs) for neural interfaces and biosensing applications. Oxidized CNFs were utilized as dopants of PEDOT to prepare the composite coating through electrochemical deposition on microelectrodes arrays (MEA). The experimental results of this study showed that PEDOT:CNF microelectrodes exhibit remarkable electrochemical properties, combining low impedance, high surface area, high charge injection capability and reliable neurotransmitters monitoring using amperometric techniques. Taken together, these results suggest the great potential of PEDOT:CNF composite for developing next-generation multifunctional microelectrodes for applications in neural therapies.•A simple approach for the electrochemical synthesis of PEDOT:CNF composite material on microelectrodes for neural interfaces and neurochemical sensing.•PEDOT:CNF microelectrodes exhibit remarkable electrochemical properties, combining low impedance and high charge injection capabilities.•PEDOT:CNF microelectrodes allowed the reliable detection of neurotransmitters with improved sensitivity.

Carbon nanofiber-PEDOT composite films as novel microelectrode for neural interfaces and biosensing.

A clear need exists for novel nanostructured materials that are capable to meet the performance criteria of a number of neuronal therapies including neural recording, stimulation and sensing of bioactive molecules at the electrode-tissue interface. By combining Poly (3,4-ethylenedioxythiophene) (PEDOT), with Carbon Nanofibers (CNFs), we demonstrate a versatile approach for the synthesis of a novel composite material PEDOT:CNF with remarkable electrochemical properties, combining low impedance, high surface area, high charge injection capability and reliable neurotransmitters monitoring using amperometric techniques. The oxidized CNFs were utilized as dopants of PEDOT to prepare the composite coatings through electrochemical deposition on neural microelectrodes arrays (MEA). The PEDOT:CNF modified microelectrodes demonstrated the low specific impedance of 1.28 MΩ µm2 at 1 kHz and results in unrivalled charge injection limit of 10.03 mC/cm2 when compared to other reported organic electrode nanomaterials. Furthermore, amperometric detection performances were determined for the neurotransmitters dopamine and serotonin, exhibiting linear concentration range from 0.1 to 9 µM and from 0.06 to 9 µM respectively, high sensitivities (44.54 pA/nM.µm2 and 71.08 pA/nM.µm2, respectively) and low detection limits (0.045 µM and 0.056 µM, respectively). Cell viability was investigated on PEDOT:CNF coated microelectrodes to show that the composite material does not advocate any cytotoxicity. Taken together, these results suggest the great potential of PEDOT:CNF composite for developing next-generation multifunctional microelectrodes for applications in neural therapies.

Unprecedented switching endurance affords for high-resolution surface temperature mapping using a spin-crossover film.

Temperature measurement at the nanoscale is of paramount importance in the fields of nanoscience and nanotechnology, and calls for the development of versatile, high-resolution thermometry techniques. Here, the working principle and quantitative performance of a cost-effective nanothermometer are experimentally demonstrated, using a molecular spin-crossover thin film as a surface temperature sensor, probed optically. We evidence highly reliable thermometric performance (diffraction-limited sub-µm spatial, µs temporal and 1 °C thermal resolution), which stems to a large extent from the unprecedented quality of the vacuum-deposited thin films of the molecular complex [Fe(HB(1,2,4-triazol-1-yl)3)2] used in this work, in terms of fabrication and switching endurance (>107 thermal cycles in ambient air). As such, our results not only afford for a fully-fledged nanothermometry method, but set also a forthcoming stage in spin-crossover research, which has awaited, since the visionary ideas of Olivier Kahn in the 90's, a real-world, technological application.

Recording local field potential and neuronal activity with tetrodes in epileptic patients.

BACKGROUND: Recordings with tetrodes have proven to be more effective in isolating single neuron spiking activity than with single microwires. However, tetrodes have never been used in humans. We report on the characteristics, safety, compatibility with clinical intracranial recordings in epileptic patients, and performance, of a new type of hybrid electrode equipped with tetrodes. NEW METHOD: 240 standard clinical macroelectrodes and 102 hybrid electrodes were implanted in 28 patients. Hybrids (diameter 800 µm) are made of 6 or 9 macro-contacts and 2 or 3 tetrodes (diameter 70-80 µm). RESULTS: No clinical complication or adverse event was associated with the hybrids. Impedance and noise of recordings were stable over time. The design enabled multiscale spatial analyses that revealed physiopathological events which were sometimes specific to one tetrode, but could not be recorded on the macro-contacts. After spike sorting, the single-unit yield was similar to other hybrid electrodes and was sometimes as high as >10 neurons per tetrode. COMPARISON WITH EXISTING METHOD(S): This new hybrid electrode has a smaller diameter than other available hybrid electrodes. It provides novel spatial information due to the configuration of the tetrodes. The single-unit yield appears promising. CONCLUSIONS: This new hybrid electrode is safe, easy to use, and works satisfactorily for conducting multi-scale seizure and physiological analyses.

Heat Capacity and Thermal Damping Properties of Spin-Crossover Molecules: A New Look at an Old Topic.

The thermally induced spin-crossover (SCO) phenomenon in transition metal complexes is an entropy-driven process, which has been extensively studied through calorimetric methods. Yet, the excess heat capacity associated with the molecular spin-state switching has never been explored for practical applications. Herein, the thermal damping effect of an SCO film is experimentally assessed by monitoring the transient heating response of SCO-coated metallic microwires, Joule-heated by current pulses. A damping of the wire temperature, up to 10%, is evidenced on a time scale of tens of microseconds due to the spin-state switching of the molecular film. Fast heat-charging dynamics and negligible fatigability are demonstrated, which, together with the solid-solid nature of the spin transition, appear as promising features for achieving thermal energy management applications in functional devices.

A review on mechanical considerations for chronically-implanted neural probes.

This review intends to present a comprehensive analysis of the mechanical considerations for chronically-implanted neural probes. Failure of neural electrical recordings or stimulation over time has shown to arise from foreign body reaction and device material stability. It seems that devices that match most closely with the mechanical properties of the brain would be more likely to reduce the mechanical stress at the probe/tissue interface, thus improving body acceptance. The use of low Young's modulus polymers instead of hard substrates is one way to enhance this mechanical mimetism, though compliance can be achieved through a variety of means. The reduction of probe width and thickness in comparison to a designated length, the use of soft hydrogel coatings and the release in device tethering to the skull, can also improve device compliance. Paradoxically, the more compliant the device, the more likely it will fail during the insertion process in the brain. Strategies have multiplied this past decade to offer partial or temporary stiffness to the device to overcome this buckling effect. A detailed description of the probe insertion mechanisms is provided to analyze potential sources of implantation failure and the need for a mechanically-enhancing structure. This leads us to present an overview of the strategies that have been put in place over the last ten years to overcome buckling issues. Particularly, great emphasis is put on bioresorbable polymers and their assessment for neural applications. Finally, a discussion is provided on some of the key features for the design of mechanically-reliable, polymer-based next generation of chronic neuroprosthetic devices.

Spray-coated carbon nanotube carpets for creeping reduction of conducting polymer based artificial muscles.

During cyclic actuation, conducting polymer based artificial muscles are often creeping from the initial movement range. One of the likely reasons of such behaviour is unbalanced charging during conducting polymer oxidation and reduction. To improve the actuation reversibility and subsequently the long time performance of ionic actuators, we suggest using spray-coated carbon nanotube (CNT) carpets on the surface of the conducting polymer electrodes. We show that carbon nanotubes facilitate a conducting polymer redox reaction and improve its reversibility. Consequently, in the long term, charge accumulation in the polymer film is avoided leading to a significantly improved lifetime performance during cycling actuation. To our knowledge, it is the first time a simple solution to an actuator creeping problem has been suggested.

High Spatial Resolution Imaging of Transient Thermal Events Using Materials with Thermal Memory.

The working principle of a new kind of nanothermometer is experimentally demonstrated using bistable materials with thermal memory. This thermometry approach allows for acquiring sub-wavelength resolution images of fast, transient heating events.

Hybrid PVDF/PVDF-graft-PEGMA Membranes for Improved Interface Strength and Lifetime of PEDOT:PSS/PVDF/Ionic Liquid Actuators.

The exploitation of soft conducting polymer-based actuators suffers from two main shortcomings: their short life cycle and the reproducibility of the fabrication techniques. The short life cycle usually results from the delamination of the components due to stresses at the interface during the actuation. In this work, to achieve strong adhesion to poly(3,4- ethylenedioxythiophene) poly(styrenesulfonate) ( PEDOT: PSS) electrodes, the wetting properties of the surface of a polyvinylidene fluoride (PVDF) membrane are improved using argon-plasma-induced surface polymerization of poly(ethylene glycol) monomethyl ether methacrylate (PEGMA). Hybrid membranes are created with hydrophilic PVDF-graft-PEGMA outer surfaces and hydrophobic bulk. The width of each layer is controlled by spray coating, as it allows for the deposition of the reaction precursor to a certain depth. Subsequently, a PEDOT: PSS water solution fills the pores of the functionalized part of the membrane and a mixing layer between PEDOT: PSS and PVDF is created. We also show that PVDF-graft-PEGMA copolymers play an important role in binding the membrane to the electrodes and that direct mechanical interlocking in the pores can further improve the adhesion. Finally, PEDOT: PSS/PVDF-graft-PEGMA/PEDOT:PSS actuators are made by simple solution casting. They are capable of producing high strains of 0.6% and show no signs of delamination after more than 150 h or 10(4) actuation cycles. Furthermore, the preservation of the hydrophobic membrane in between two PEDOT: PSS layers increases the resistance between them from 0.36 Ω to 0.16 MΩ, thus drastically modifying the power dissipation of the actuators.

AFM imaging of molecular spin-state changes through quantitative thermomechanical measurements.

Quantitative atomic force microscopy is used in conjunction with microwire heaters for high-resolution imaging of the Young's modulus changes across the spin-state transition. When going from the high spin to the low spin state, a significant stiffening is observed.

Note: A scanning thermal probe microscope that operates in liquids.

We have developed a scanning thermal probe microscope that operates in liquid environments. The thermal sensor is a fluorescent particle glued at the end of a sharp tungsten tip. Since light emission is a strongly thermally sensitive effect, the measurement of the particle fluorescence variations allows the determination of the temperature. No electrical wiring of the probe is needed. As a demonstrative example, we have measured the temperature map of a Joule-heated microheater immersed in a water∕glycerol solution. Both topographical and thermal images are obtained with a good sensitivity.

Scanning thermal imaging by near-field fluorescence spectroscopy.

A scanning thermal microscope that uses a fluorescent particle as a temperature probe has been developed. The particle, made of a rare-earth ion-doped fluoride glass, is glued at the extremity of a sharp tungsten tip and scanned on the surface of an electronic device. The temperature of the device is determined by measuring the fluorescence spectrum of the particle at every point on the surface and by comparing the intensity variations of two emission lines. As an example, we will show some images obtained on a nickel stripe 1 microm wide, heated by an electrical current. A good agreement is observed with a simulation of the temperature field on the device.

Direct patterning of molecularly imprinted microdot arrays for sensors and biochips.

We have used fountain pen microlithography to deposit arrays of molecularly imprinted polymer microdots on flat substrates. We visualize analyte binding to the dots by fluorescence microscopy with the aid of fluorescein as a model analyte. Elution and readsorption of the analyte to the MIP dots were possible if the porosity of the dots was improved by a sacrificial polymeric porogen. The imprinting effect was confirmed by using compounds structurally related to fluorescein. In addition, we show with another MIP specific to 2,4-D that, apart from the direct measurement of the binding of fluorescent compounds, a competitive immunoassay-type format can also be used to transduce the binding. We believe that this technique has a strong potential for the fabrication of biomimetic microchips and other types of integrated biosensors.