Electrical Stimulation Of Cells Research Articles

Promoting Human Intestinal Organoid Formation and Stimulation Using Piezoelectric Nanofiber Matrices.

Human organoid model systems have changed the landscape of developmental biology and basic science. They serve as a great tool for human specific interrogation. In order to advance our organoid technology, we aimed to test the compatibility of a piezoelectric material with organoid generation, because it will create a new platform with the potential for sensing and actuating organoids in physiologically relevant ways. We differentiated human pluripotent stem cells into spheroids following the traditional human intestinal organoid (HIO) protocol atop a piezoelectric nanofiber scaffold. We observed that exposure to the biocompatible piezoelectric nanofibers promoted spheroid morphology three days sooner than with the conventional methodology. At day 28 of culture, HIOs grown on the scaffold appeared similar. Both groups were readily transplantable and developed well-organized laminated structures. Graft sizes between groups were similar. Upon characterizing the tissue further, we found no detrimental effects of the piezoelectric nanofibers on intestinal patterning or maturation. Furthermore, to test the practical feasibility of the material, HIOs were also matured on the nanofiber scaffolds and treated with ultrasound, which lead to increased cellular proliferation which is critical for organoid development and tissue maintenance. This study establishes a proof of concept for integrating piezoelectric materials as a customizable platform for on-demand electrical stimulation of cells using remote ultrasonic waveforms in regenerative medicine.

Graphene-Based Aerogels for Biomedical Application.

Aerogels are three-dimensional solid networks with incredibly low densities, high porosity, and large specific surface areas. These aerogels have both nanoscale and macroscopic interior structures. Combined with graphene, the aerogels show improved mechanical strength, electrical conductivity, surface area, and adsorption capacity, making them ideal for various biomedical applications. The graphene aerogel has a high drug-loading capacity due to its large surface area, and the porous structure enables controlled drug release over time. The presence of graphene makes it a suitable material for wound dressings, blood coagulation, and bilirubin adsorption. Additionally, graphene's conductivity can help in the electrical stimulation of cells for improved tissue regeneration, and it is also appropriate for biosensors. In this review, we discuss the preparation and advantages of graphene-based aerogels in wound dressings, drug delivery systems, bone regeneration, and biosensors.

Enhanced Proliferation and Differentiation of Human Osteoblasts by Remotely Controlled Magnetic-Field-Induced Electric Stimulation Using Flexible Substrates.

With the progressive aging of the population, bone fractures are an increasing major health concern. Diverse strategies are being studied to reduce the recovery times using nonaggressive treatments. Electrical stimulation (either endogenous or externally applied electric pulses) has been found to be effective in accelerating bone cell proliferation and differentiation. However, the direct insertion of electrodes into tissues can cause undesirable inflammation or infection reactions. As an alternative, magnetoelectric heterostructures (wherein magnetic fields are applied to induce electric polarization) could be used to achieve electric stimulation without the need for implanted electrodes. Here, we develop a magnetoelectric platform based on flexible kapton/FeGa/P(VDF-TrFE) (flexible substrate/magnetostrictive layer/ferroelectric layer) heterostructures for remote magnetic-field-induced electric field stimulation of human osteoblast cells. We show that the use of flexible supports overcomes the clamping effects that typically occur when analogous magnetoelectric structures are grown onto rigid substrates (which preclude strain transfer from the magnetostrictive to the ferroelectric layers). The study of the diverse proliferation and differentiation markers evidence that in all the stages of bone formation (cell proliferation, extracellular matrix maturation, and mineralization), the electrical stimulation of the cells results in a remarkably better performance. The results pave the way for novel strategies for remote cell stimulation based on flexible platforms not only in bone regeneration but also in many other applications where electrical cell stimulation may be beneficial (e.g., neurological diseases or skin regeneration).

Stimuli-Responsive 3D Printable Conductive Hydrogel: A Step toward Regulating Macrophage Polarization and Wound Healing.

Conductive hydrogels (CHs) are promising alternatives for electrical stimulation of cells and tissues in biomedical engineering. Wound healing and immunomodulation are complex processes that involve multiple cell types and signaling pathways. 3D printable conductive hydrogels have emerged as an innovative approach to promote wound healing and modulate immune responses. CHs can facilitate electrical and mechanical stimuli, which can be beneficial for altering cellular metabolism and enhancing the efficiency of the delivery of therapeutic molecules. This review summarizes the recent advances in 3D printable conductive hydrogels for wound healing and their effect on macrophage polarization. This report also discusses the properties of various conductive materials that can be used to fabricate hydrogels to stimulate immune responses. Furthermore, this review highlights the challenges and limitations of using 3D printable CHs for future material discovery. Overall, 3D printable conductive hydrogels hold excellent potential for accelerating wound healing and immune responses, which can lead to the development of new therapeutic strategies for skin and immune-related diseases.

PEDOT-Coated PLA Fibers Electrospun from Solutions Incorporating Fe(III)Tosylate in Different Solvents by Vapor-Phase Polymerization for Neural Regeneration.

Therapeutic solutions for injuries in the peripheral nervous system are limited and not existing in the case of the central nervous system. The electrical stimulation of cells through a cell-supporting conductive scaffold may contribute to new therapeutic solutions for nerve regeneration. In this work, biocompatible Polylactic acid (PLA) fibrous scaffolds incorporating Fe(III)Tosylate (FeTos) were produced by electrospinning a mixture of PLA/FeTos solutions towards a rotating cylinder, inducing fiber alignment. Fibers were coated with the conductive polymer Poly(3,4 ethylenedioxythiophene) (PEDOT) formed by vapor-phase polymerization of EDOT at 70 °C for 2 h. Different solvents (ETH, DMF and THF) were used as FeTos solvents to investigate the impact on the scaffold's conductivity. Scaffold conductivity was estimated to be as high as 1.50 × 10-1 S/cm when FeTos was dissolved in DMF. In vitro tests were performed to evaluate possible scaffold cytotoxicity, following ISO 10993-5, revealing no cytotoxic effects. Differentiation and growth of cells from the neural cell line SH-SY5Y seeded on the scaffolds were also assessed, with neuritic extensions observed in cells differentiated in neurons with retinoic acid. These extensions tended to follow the preferential alignment of the scaffold fibers.

Magnetic manipulation of Fe3O4@BaTiO3 nanochains to regulate extracellular topographical and electrical cues.

Magnetic fields play an essential role in material science and biomedical engineering. Magnetic-responsive materials can be arranged orderly in matrix to realize the construction of an aligned scaffold under magnetic induction. However, a single topological cue is insufficient to activate neural tissue regeneration, demanding more cues to promote regeneration synergistically, such as electrical stimulation and a biomimetic matrix. Herein, we propose one-dimensional (1D) magnetoelectric Fe3O4@BaTiO3 nanochains with controllable lengths under the regulation of a magnetic field. These nanochains can be oriented in the biomimetic hydrogel under magnetic guidance and induce the hydrogel microfiber to align along the direction of the nanochains, which is beneficial for cell-oriented outgrowth. This aligned hydrogel enabled wireless electrical stimulation mediated by magnetoelectric nanochains under magnetic stimulation, thereby activating the voltage-gated ion channel. Consequently, topological and electrical cues in this multifunctional biomimetic hydrogel synergistically enhanced the expression of neural functional proteins, facilitating synapse remodeling and neural regeneration. Predictably, the construction of multifunctional hydrogels based on low-cost and facile synthesis of magnetoelectric nanochains is an emerging patient-friendly and effective therapeutic strategy for neural or other tissue regeneration. STATEMENT OF SIGNIFICANCE: A facile and controllable magnetic strategy is established to manipulate 1D nanomaterial growth, matrix topography, and wireless electrical stimulation of cells. First, the magnetic-assisted interface co-assembly was used to control the length of Fe3O4@BaTiO3 nanochains with enhanced magnetoelectric effect. Then, the motion of the magnetic-induced nanochains guided the orientation of nanofibers in a 3D biomimetic hydrogel matrix. Finally, wireless electrical signals and topological cues in the biomimetic matrix synergistically promoted orderly aligned cell outgrowth and membrane depolarization by Ca2+ influx, thus enhancing nerve cell synaptic plasticity and functional expression. Consequently, this work provides a conceptual strategy from material design to extracellular matrix signal manipulation and synergistic induction of tissue regeneration.

Designing Electrical Stimulation Platforms for Neural Cell Cultivation Using Poly(aniline): Camphorsulfonic Acid.

Electrical stimulation is a powerful strategy to improve the differentiation of neural stem cells into neurons. Such an approach can be implemented, in association with biomaterials and nanotechnology, for the development of new therapies for neurological diseases, including direct cell transplantation and the development of platforms for drug screening and disease progression evaluation. Poly(aniline):camphorsulfonic acid (PANI:CSA) is one of the most well-studied electroconductive polymers, capable of directing an externally applied electrical field to neural cells in culture. There are several examples in the literature on the development of PANI:CSA-based scaffolds and platforms for electrical stimulation, but no review has examined the fundamentals and physico-chemical determinants of PANI:CSA for the design of platforms for electrical stimulation. This review evaluates the current literature regarding the application of electrical stimulation to neural cells, specifically reviewing: (1) the fundamentals of bioelectricity and electrical stimulation; (2) the use of PANI:CSA-based systems for electrical stimulation of cell cultures; and (3) the development of scaffolds and setups to support the electrical stimulation of cells. Throughout this work, we critically evaluate the revised literature and provide a steppingstone for the clinical application of the electrical stimulation of cells using electroconductive PANI:CSA platforms/scaffolds.

Electrically stimulated gene expression under exogenously applied electric fields.

Introduction: Electrical stimulation, the application of an electric field to cells and tissues grown in culture to accelerate growth and tight junction formation among endothelial cells, could be impactful in cardiovascular tissue engineering, allotransplantation, and wound healing. Methods: Using Electrical Cell Stimulation And Recording Apparatus (ECSARA), the exploration of the stimulatory influences of electric fields of different magnitude and frequencies on growth and proliferation, trans endothelial electrical resistance (TEER) and gene expression of human endothelia cells (HUVECs) were explored. Results: Within the range of endogenous electrical pulses studied, frequency was found to be more significant (p = 0.05) than voltage in influencing HUVEC gene expression. Localization of Yes Associated Protein (YAP) and expression of CD-144 are shown to be consistent with temporal manifestations of TEER. Discussion: This work introduces the field of electromics, the study of cellular gene expression profiles and their implications under the influence of exogenously applied electric fields. Homology of electrobiology and mechanobiology suggests use of such exogenous cues in tissue and regenerative engineering.

Poly(l‐Lactic Acid) Nanofiber‐Based Multilayer Film for the Electrical Stimulation of Nerve Cells

AbstractPoly(l‐lactic acid) (PLLA) films have excellent piezoelectric properties, but the strong hydrophobicity of the surface makes it difficult for cells to attach there. PLLA nanofibers have good biocompatibility, but the weak piezoelectric coefficient limits the ability of the nanofibers to stimulate cell growth. Therefore, the PLLA piezoelectric film is combined with the PLLA nanofibers to make a multilayer film. In our tests, the piezoelectric output of the multilayer film ≈260 mV. In the biological experiments section, without piezoelectric stimulation, the cell length on the nanofibers is approximately twice that of the cells in the blank control group. The length of cells cultured on piezoelectric‐based stimulated nanofibers is more than twice that of cells cultured on nanofibers without piezoelectric stimulation. Therefore, it is confirmed that under the dual action of nanofiber guidance and piezoelectric stimulation, the growth rate of cells is four times faster than that in ordinary Petri dishes. Intracellular calcium imaging experiments confirmed that the concentration of Ca2+ in electrically stimulated cells is approximately twice that of ordinary cells. It is also confirmed that piezoelectric materials can complete electrical stimulation of cells in indirect contact with cells.

Effects of Electrical Stimulation of the Cell: Wound Healing, Cell Proliferation, Apoptosis, and Signal Transduction.

Electrical stimulation of the cell can have a number of different effects depending on the type of cell being stimulated. In general, electrical stimulation can cause the cell to become more active, increase its metabolism, and change its gene expression. For example, if the electrical stimulation is of low intensity and short duration, it may simply cause the cell to depolarize. However, if the electrical stimulation is of high intensity or long duration, it may cause the cell to become hyperpolarized. The electrical stimulation of cells is a process by which an electrical current is applied to cells in order to change their function or behavior. This process can be used to treat various medical conditions and has been shown to be effective in a number of studies. In this perspective, the effects of electrical stimulation on the cell are summarized.

Development of 3D printable graphene oxide based bio-ink for cell support and tissue engineering.

Tissue engineered constructs can serve as in vitro models for research and replacement of diseased or damaged tissue. As an emerging technology, 3D bioprinting enables tissue engineering through the ability to arrange biomaterials and cells in pre-ordered structures. Hydrogels, such as alginate (Alg), can be formulated as inks for 3D bioprinting. However, Alg has limited cell affinity and lacks the functional groups needed to promote cell growth. In contrast, graphene oxide (GO) can support numerous cell types and has been purported for use in regeneration of bone, neural and cardiac tissues. Here, GO was incorporated with 2% (w/w) Alg and 3% (w/w) gelatin (Gel) to improve 3D printability for extrusion-based 3D bioprinting at room temperature (RT; 25°C) and provide a 3D cellular support platform. GO was more uniformly distributed in the ink with our developed method over a wide concentration range (0.05%-0.5%, w/w) compared to previously reported GO containing bioink. Cell support was confirmed using adipose tissue derived stem cells (ADSCs) either seeded onto 3D printed GO scaffolds or encapsulated within the GO containing ink before direct 3D printing. Added GO was shown to improve cell-affinity of bioinert biomaterials by providing more bioactive moieties on the scaffold surface. 3D cell-laden or cell-seeded constructs showed improved cell viability compared to pristine (without GO) bio-ink-based scaffolds. Our findings support the application of GO for novel bio-ink formulation, with the potential to incorporate other natural and synthetic materials such as chitosan and cellulose for advanced in situ biosensing, drug-loading and release, and with the potential for electrical stimulation of cells to further augment cell function.

G-Optrode Bio-Interfaces for Non-Invasive Optical Cell Stimulation: Design and Evaluation.

Biocompatibility and potential efficacy in biological applications rely on the bio-interactions of graphene nanoparticles with biological tissues. Analyzing and modulating cellular and device-level activity requires non-invasive electrical stimulation of cells. To address these needs, G-optrodes, bio-interfaces based on graphene, have been developed. These devices use light to stimulate cells without modifying their genetic code. Optoelectronic capabilities, in particular the capacity to transform light energy into electrical energy, will be maintained throughout the procedures of neural stimulation. G-optrodes have also been studied as thin films on a range of substrates, and they have been designed to function at a very small scale. This study examines the impact of G-optrode-based substrate designs on the optical stimulation of pheochromocytoma (PC-12). Graphene electrodes, known as G-optrodes, are responsible for converting light into electrical pulses with stimulating effects. G-optrode bio-interfaces provide a stimulus that is independent of wavelength range but is sensitive to changes in illuminance. The authors have performed a comprehensive investigation based on the correct effects of the medication in vitro, employing substrate-based G-optrode biointerfaces. In substrate-based systems, the authors have proven that graphene is biocompatible. PC-12 cells were cultured on graphene for 7 days. Based on the findings, 20-nm and 50-nm thick G-optrodes are being studied for possible use in biological and artificial retinal applications. The findings of this study highlight the significance of biocompatibility in the selection and use of G-optrodes for biomedical purposes.

Using a Digital Twin of an Electrical Stimulation Device to Monitor and Control the Electrical Stimulation of Cells in vitro.

Electrical stimulation for application in tissue engineering and regenerative medicine has received increasing attention in recent years. A variety of stimulation methods, waveforms and amplitudes have been studied. However, a clear choice of optimal stimulation parameters is still not available and is complicated by ambiguous reporting standards. In order to understand underlying cellular mechanisms affected by the electrical stimulation, the knowledge of the actual prevailing field strength or current density is required. Here, we present a comprehensive digital representation, a digital twin, of a basic electrical stimulation device for the electrical stimulation of cells in vitro. The effect of electrochemical processes at the electrode surface was experimentally characterised and integrated into a numerical model of the electrical stimulation. Uncertainty quantification techniques were used to identify the influence of model uncertainties on relevant observables. Different stimulation protocols were compared and it was assessed if the information contained in the monitored stimulation pulses could be related to the stimulation model. We found that our approach permits to model and simulate the recorded rectangular waveforms such that local electric field strengths become accessible. Moreover, we could predict stimulation voltages and currents reliably. This enabled us to define a controlled stimulation setting and to identify significant temperature changes of the cell culture in the monitored voltage data. Eventually, we give an outlook on how the presented methods can be applied in more complex situations such as the stimulation of hydrogels or tissue in vivo.

Cell-Traction-Triggered On-Demand Electrical Stimulation for Neuron-Like Differentiation.

Electromechanical interaction of cells and extracellular matrix are ubiquitous in biological systems. Understanding the fundamentals of this interaction and feedback is critical to design next-generation electroactive tissue engineering scaffold. Herein, based on elaborately modulating the dynamic mechanical forces in cell microenvironment, the design of a smart piezoelectric scaffold with suitable stiffness analogous to that of collagen for on-demand electrical stimulation is reported. Specifically, it generated a piezoelectric potential, namely a piezopotential, to stimulate stem cell differentiation with cell traction as a loop feedback signal, thereby avoiding the unfavorable effect of early electrical stimulation on cell spreading and adhesion. This is the first time to adapt to the dynamic microenvironment of cells and meet the electrical stimulation of cells in different states by a constant scaffold, diminishing the cumbersomeness of inducing material transformation or trigging by an external stimulus. This in situ on-demand electrical stimulation based on cell-traction-mediated piezopotential paves the way for smart scaffolds design and future bioelectronic therapies.

Electrical stimulation of titanium to promote stem cell orientation, elongation and osteogenesis

Electrical stimulation of cells allows exogenous electric signals as stimuli to manipulate cell growth, preferential orientation and bone remodelling. In this study, commercially pure titanium discs were utilised in combination with a custom-built bioreactor to investigate the cellular responses of human mesenchymal stem cells via in-vitro functional assays. Finite element analysis revealed the homogeneous delivery of electric field in the bioreactor chamber with no detection of current density fluctuation in the proposed model. The custom-built bioreactor with capacitive stimulation delivery system features long-term stimulation with homogeneous electric field, biocompatible, sterilisable, scalable design and cost-effective in the manufacturing process. Using a continuous stimulation regime of 100 and 200 mV/mm on cp Ti discs, viability tests revealed up to an approximately 5-fold increase of cell proliferation rate as compared to non-stimulated controls. The human mesenchymal stem cells showed more elongated and differentiated morphology under this regime, with evidence of nuclear elongation and cytoskeletal orientation perpendicular to the direction of electric field. The continuous stimulation did not cause pH fluctuations and hydrogen peroxide production caused by Faradic reactions, signifying the suitability for long-term toxic free stimulation as opposed to the commonly used direct stimulation regime. An approximate of 4-fold increase in alkaline phosphatase production and approximately 9-fold increase of calcium deposition were observed on 200 mV/mm exposed samples relative to non-stimulated controls. It is worth noting that early stem cell differentiation and matrix production were observed under the said electric field even without the presence of chemical inductive growth factors. Statement of significanceThis manuscript presents a study on combining pure titanium (primarily preferred as medical implant materials) and electrical stimulation in a purpose-built bioreactor with capacitive stimulation delivery system. A continuous capacitive stimulation regime on titanium disc has resulted in enhanced stem cell orientation, nuclei elongation, proliferation and differentiation as compared to non-stimulated controls. We believe that this manuscript creates a paradigm for future studies on the evolution of healthcare treatments in the area of targeted therapy on implantable and wearable medical devices through tailored innovative electrical stimulation approach, thereby influencing therapeutic conductive and electroactive biomaterials research prospects and development.

Remotely controlled self-powering electrical stimulators for osteogenic differentiation using bone inspired bioactive piezoelectric whitlockite nanoparticles

Endogenous electric fields naturally exist in our body and plays a vital role especially in the development and regeneration of bones. Therefore, piezoelectric bone implants are gaining ample attention due to its inherent electrical signal generation, but generally they lack bioactivity, resorption, and ECM like composition. To address this, we evoke ‘piezoelectricity’ in whitlockite (Ca 18 Mg 2 (HPO 4 ) 2 (PO 4 ) 12 ) nanoparticles (WH NPs) for the first time in literature. WH NPs are the second most-abundant inorganic bone mineral and reported for intermediate resorption compared to hydroxyapatite and tricalcium phosphate. Systematic electrical studies reveal that WH NPs annealed at 750 °C (PWH-750) exhibit superior ferroelectric and dielectric characteristics and produce electrical signals analogous to native tissues when triggered using FDA approved low-intensity pulsed ultrasound (LIPUS) noninvasively. The energy generation performance of Piezoelectric WH based self powered nanogenerators are analyzed and demonstrated to power the commercial LED upon LIPUS stimulation. The in vitro studies with pre-osteoblast MC3T3-E1 cells co-cultured with piezoelectric WH NPs exhibit increased ALP activity, calcium mineralization, and osteogenic gene expression along with significant upregulation of Piezo1, and TRPV4 expressions. This confirms the enhanced osteogenic differentiation compared to the control WH nanoparticles due to the remotely activated self powering capacity of piezoelectric WH NPs and thereby produce bioelectric signals analogous to native tissues. Thus, the study evidences the development of a potential bioactive piezoelectric ceramic with extensive applicability for future clinical translation. • Development of piezoelectric whitlockite nanoparticles for self-powered electrical cell stimulation. • The study also reports the development of the unique piezoelectric nanogenerator (PENG) based on biocompatible WH NPs. • LIPUS mediated electric field produced by the piezoelectric WH NPs promotes osteoblast proliferation and differentiation. • The study confirms the enhanced osteogenic differentiation via Piezo1 and TRPV4 mechanosensitive ion channels. • A new perspective in the field of regenerative medicine through self-powered electrical stimulation to cells.

Self-activated microbatteries to promote cell death through local electrical stimulation

Abstract Electrical stimulation of cells offers a viable alternative route to treat diseases like cancer that account for several deaths despite sophisticated treatments. While micro/nanoscale systems have demonstrated to regulate cell activity by inducing electrical signals, many of these rely on external excitation sources for operation. In this work, we present an array of Al-H2O based microbatteries of dimensions smaller than a single cell to induce localized electrical impulses by involving no excitation sources outside the cellular environment, i.e., self-stimulation, for a limited operation time. The fabricated structure allows microbattery activation, i.e., produces a voltage or current flow, on contact with the ionic species in biological medium. The study explores the response of human osteosarcoma cells (Saos-2) under the influence of these generated electrical impulses. The microbatteries allowed proliferation of Saos-2 cells when configured to operate in an open-circuit fashion, while they induced cell death in a short-circuited operation due to a current flow causing a drastic reduction in cell viability to 13.5%. The self-stimulated current produced a profound cytotoxic effect up to 24 h of incubation before the microbatteries became inactive. An up-scaled model and fabricated test-structure further explores the electrochemical characteristics of Al-H2O based batteries and their effect on relevant parameters like pH. The overall results suggest prospects for a non-invasive treatment in cancer therapy, neuromuscular system, neurological disorders, chronic treatments, tissue regeneration and other electrically active systems by the application of a self-stimulated electrical signal.

Piezoelectric and Magnetoelectric Scaffolds for Tissue Regeneration and Biomedicine: A Review.

Electric fields are ubiquitous throughout the body, playing important role in a multitude of biological processes including osteo-regeneration, cell signaling, nerve regeneration, cardiac function, and DNA replication. An increased understanding of the role of electric fields in the body has led to the development of devices for biomedical applications that incorporate electromagnetic fields as an intrinsically novel functionality (e.g., bioactuators, biosensors, cardiac/neural electrodes, and tissues scaffolds). However, in the majority of the aforementioned devices, an implanted power supply is necessary for operation, and therefore requires highly invasive procedures. Thus, the ability to apply electric fields in a minimally invasive manner to remote areas of the body remains a critical and unmet need. Here, we report on the potential of magnetoelectric (ME)-based composites to overcome this challenge. ME materials are capable of producing localized electric fields in response to an applied magnetic field, which the body is permeable to. Yet, the use of ME materials for biomedical applications is just beginning to be explored. Here, we present on the potential of ME materials to be utilized in biomedical applications. This will be presented alongside current state-of-the-art for in vitro and in vivo electrical stimulation of cells and tissues. We will discuss key findings in the field, while also identifying challenges, such as the synthesis and characterization of biocompatible ME materials, challenges in experimental design, and opportunities for future research that would lead to the increased development of ME biomaterials and their applications.

Barium titanate-based bilayer functional coatings on Ti alloy biomedical implants

Piezoelectric coatings have the ability to functionalise conventional structural materials into responsive devices. Today, piezoelectric coatings have been applied to both rigid and flexible substrates for sensing, actuating, and energy harvesting applications. We envision (Ba,Ca)(Zr,Ti)O3 (BCZT) piezoelectric coatings for biomedical use such as in vivo sensing or electrical cell stimulation. However, reliable processing routes for the development of BCZT ceramics as a functionalisation coating on biomedical substrates are required. In this work, the synthesis of bilayer BCZT and CaTiO3 ceramic coatings on Ti6Al4V metal substrates via spray-deposition and heat-treatment was investigated. For thin coatings, reactions at the metal/ceramic interface led to the development of a porous interface reaction region partly consisting of CaO. The hygroscopicity of CaO affects the adhesion of the coating to Ti6Al4V at ambient conditions. Minimisation of the kinetic contributions to these interface reactions were achieved by increasing the coating thickness.

Printed Graphene Layer as a Base for Cell Electrostimulation-Preliminary Results.

Nerve regeneration through cell electrostimulation will become a key finding in regenerative medicine. The procedure will provide a wide range of applications, especially in body reconstruction, artificial organs or nerve prostheses. Other than in the case of the conventional polystyrene substrates, the application of the current flow in the cell substrate stimulates the cell growth and mobility, supports the synaptogenesis, and increases the average length of neuron nerve fibres. The indirect electrical cell stimulation requires a non-toxic, highly electrically conductive substrate material enabling a precise and effective cell electrostimulation. The process can be successfully performed with the use of the graphene nanoplatelets (GNPs)—the structures of high conductivity and biocompatible with mammalian NE-4C neural stem cells used in the study. One of the complications with the production of inks using GNPs is their agglomeration, which significantly hampers the quality of the produced coatings. Therefore, the selection of the proper amount of the surfactant is paramount to achieve a high-quality substrate. The article presents the results of the research into the material manufacturing used in the cell electrostimulation. The outcomes allow for the establishment of the proper amount of the surfactant to achieve both high conductivity and quality of the coating, which could be used not only in electronics, but also—due to its biocompatibility—fruitfully applied to the cell electrostimulation.