Bioelectric Properties Research Articles

Wireless Stimulation of Barium Titanate@PEDOT Nanoparticles Toward Bioelectrical Modulation in Cancer.

Cancer cells possess distinct bioelectrical properties, yet therapies leveraging these characteristics remain underexplored. Herein, we introduce an innovative nanobioelectronic system combining a piezoelectric barium titanate nanoparticle core with a conducting poly(3,4-ethylenedioxythiophene) shell (BTO@PEDOT NPs), designed to modulate cancer cell bioelectricity through noninvasive, wireless stimulation. Our hypothesis is that acting as nanoantennas, BTO@PEDOT NPs convert mechanical inputs provided by ultrasound (US) into electrical signals, capable of interfering with the bioelectronic circuitry of two human breast cancer cell lines, MCF-7 and MDA-MB-231. Upon US stimulation, the viability of MCF-7 and MDA-MB-231 cells treated with 200 μg mL-1 BTO@PEDOT NPs and US reduced significantly to 31% and 24%, respectively, while healthy human mammary fibroblasts (HMF) were unaffected by the treatment. Subsequent assays shed light on how this approach could interact with cell's bioelectrical mechanisms, namely, by increasing intracellular reactive oxygen species (ROS) and calcium concentrations. Furthermore, this system was able to polarize cancer cell membranes, halting their cell cycle and potentially harnessing their tumorigenic characteristics. These findings underscore the crucial role of bioelectricity in cancer progression and highlight the potential of nanobioelectronic systems as an emerging and promising strategy for cancer intervention.

Piezoelectric Nanoarrays with Mechanical-Electrical Coupling Microenvironment for Innervated Bone Regeneration.

The involvement of neurons in the peripheral nervous system is crucial for bone regeneration. Mimicking extracellular matrix cues provides a more direct and effective strategy to regulate neuronal activity and enhance bone regeneration. However, the simultaneous coupling of the intrinsic mechanical-electrical microenvironment of implants to regulate innervated bone regeneration has been largely neglected. Inspired by the mechanical and bioelectric properties of the bone microenvironment, this study constructed a mechanical-electrical coupling microenvironment (M-E) model based on barium titanate piezoelectric nanoarrays, which could effectively promote innervated bone regeneration. The study found that the mechanical microenvironment provided by the nanostructure, coupled with the electrical microenvironment provided by the piezoelectric properties, created a controllable M-E. In vitro cell experiments demonstrated that this coupled microenvironment activated Piezo2 and VGCC ion channels, promoted calcium influx in DRG neurons, and activated downstream PI3K-AKT and RAS pathways. This cascade of events led to the synthesis and release of CGRP in sensory nerves, ultimately enhancing the osteogenic differentiation of BMSCs. This work not only broadens the current understanding of biomaterials that mimic the bone extracellular matrix but also provides new insights into innervated bone regeneration.

Bioimpedance Measurements of Fibrotic and Acutely Injured Lung Tissues.

In injured and diseased tissues, changes in molecular and cellular compositions, as well as tissue architecture, lead to alterations in both physiological and physical characteristics. Notably, the electrical properties of tissues, which can be characterized as bioelectrical impedance (bioimpedance), are closely linked to the health and pathological conditions of the tissues. This highlights the significant role of quantitatively characterizing these electrical properties in improving the accuracy and speed of diagnosis and prognosis. In this study, we investigate how diseases, injuries, and physical conditions can affect the electrical properties of lung tissues, using both rat and human lung tissue samples. Results showed that rat lung and trachea tissues exhibit a frequency-dependent behavior to alternating current (AC) across the frequency range of 0.1 to 300 kHz. The bioimpedance of the lung tissue increased with the level of aeration of the lung, which was manipulated by altering alveolar pressure (PALV: 1-15 cmH2O; bioimpedance level: 1.2-2.8 kΩ; AC frequency: 2 kHz). This increase is mainly because air is electrically nonconductive. The bioimpedance of rat lungs injured via intratracheal aspiration of hydrochloric acid (HCl; volume: 1 mL; AC frequency: 2 kHz) decreased by at least 82% compared to that of healthy control lungs due to accumulation of fluids inside the airspace of the injured lungs. Moreover, using decellularized lung tissues, we determined the contributions of cellular components and tissue extracellular matrix (ECM) on the electrical characteristics of the lung tissues. Specifically, we observed a considerable increase in bioimpedance in fibrotic human lung tissues due to excessive ECM deposition (healthy: 70.8 Ω ± 10.2 Ω, fibrotic: 132.1 Ω ± 15.8 Ω, frequency: 2 kHz). Overall, the findings of this study can enhance our understanding of the correlation between electrical properties and pathological lung conditions, thereby improving diagnostic and prognostic capabilities and aiding in the treatment of lung diseases and injuries. STATEMENT OF SIGNIFICANCE: The bioelectrical properties of tissue are closely linked to both its physiological and physical characteristics. This underscores the importance of quantitatively characterizing these properties to improve the accuracy and speed of diagnosis and prognosis. In this study, we investigate how the bioelectrical properties of lung tissues are affected by different physical states and pathological conditions using rat and human lung tissues. As the burden of lung diseases continues to increase, our findings can contribute to improved treatment outcomes by enabling accurate and rapid assessment of lung tissue conditions.

Morphological features of white adipose tissue in rats with different levels of energy metabolism in visceral obesity

Histomorphological changes of visceral white adipose tissue in obesity as a function of the level of energy metabolism in the body have not been sufficiently studied. The aim of this study was to investigate and compare the structural changes of visceral white adipose tissue in rats with different metabolic levels and severe visceral obesity. The study was carried out on male Wistar rats aged 3 months at the start of the experiment. Control animals received standard diet. Experimental rats were fed a high calorie diet for 12 weeks. At the end of the experiment, rats from both the control and experimental groups were divided into low and high level of energy metabolism depending on the intensity of total oxygen consumption. Histological preparations of visceral white adipose tissue were prepared according to the standard method. Histomorphometry was performed on digital images using the “Image J 1.34p” computer program. Biochemical methods were used to determine the concentration of triglycerides, lipids and cholesterol in blood serum. The method of multifrequency bioimpedance was used to assess the biophysical properties of visceral white adipose tissue. The data obtained were processed by methods of variational statistics using one-way analysis of variance. It was shown that long-term use of a high-calorie diet led to the development of visceral obesity, which was manifested by a significant increase in the weight of visceral fat and an increase in the concentration of indicators of lipid metabolism in blood serum. It was found that a high-calorie diet altered the morphological structure of the rat’s visceral white adipose tissue, leading to adipocyte hypertrophy, reduced blood volume and increased the amount of connective tissue in it. The bioelectrical properties of the visceral white adipose tissue changed, as evidenced by an increase in its electrical impedance and a decrease in its frequency dispersion coefficient. The intensity of structural, biochemical and biophysical changes in the visceral white adipose tissue was more pronounced in rats with low level of energy metabolism and depended on the degree of obesity. The results obtained are important for practical medicine in the development of new effective methods for the prevention and treatment of obesity in patients according to level of energy metabolism.

Emerging cancer therapies: targeting physiological networks and cellular bioelectrical differences with non-thermal systemic electromagnetic fields in the human body – a comprehensive review

A steadily increasing number of publications support the concept of physiological networks, and how cellular bioelectrical properties drive cell proliferation and cell synchronization. All cells, especially cancer cells, are known to possess characteristic electrical properties critical for physiological behavior, with major differences between normal and cancer cell counterparts. This opportunity can be explored as a novel treatment modality in Oncology. Cancer cells exhibit autonomous oscillations, deviating from normal rhythms. In this context, a shift from a static view of cellular processes is required for a better understanding of the dynamic connections between cellular metabolism, gene expression, cell signaling and membrane polarization as states in constant flux in realistic human models. In oncology, radiofrequency electromagnetic fields have produced sustained responses and improved quality of life in cancer patients with minimal side effects. This review aims to show how non-thermal systemic radiofrequency electromagnetic fields leads to promising therapeutic responses at cellular and tissue levels in humans, supporting this newly emerging cancer treatment modality with early favorable clinical experience specifically in advanced cancer.

Heterogeneity in oligodendrocyte precursor cell proliferation is dynamic and driven by passive bioelectrical properties

Oligodendrocyte precursor cells (OPCs) generate myelinating oligodendrocytes and are the main proliferative cells in the adult central nervous system. OPCs are a heterogeneous population, with proliferation and differentiation capacity varying with brain region and age. We demonstrate that during early postnatal maturation, cortical, but not callosal, OPCs begin to show altered passive bioelectrical properties, particularly increased inward potassium (K+) conductance, which correlates with G1 cell cycle stage and affects their proliferation potential. Neuronal activity-evoked transient K+ currents in OPCs with high inward K+ conductance potentially release OPCs from cell cycle arrest. Eventually, OPCs in all regions acquire high inward K+ conductance, the magnitude of which may underlie differences in OPC proliferation between regions, with cells being pushed into a dormant state as they acquire high inward K+ conductance and released from dormancy by synchronous neuronal activity. Age-related accumulation of OPCs with high inward K+ conductance might contribute to differentiation failure.

Maternal stress and the early embryonic microenvironment: investigating long-term cortisol effects on bovine oviductal epithelial cells using air–liquid interface culture

The oviduct epithelium is the initial maternal contact site for embryos after fertilization, offering the microenvironment before implantation. This early gestation period is particularly sensitive to stress, which can cause reduced fertility and reproductive disorders in mammals. Nevertheless, the local impact of elevated stress hormones on the oviduct epithelium has received limited attention to date, except for a few reports on polyovulatory species like mice and pigs. In this study, we focused on the effects of chronic maternal stress on cattle, given its association with infertility issues in this monoovulatory species. Bovine oviduct epithelial cells (BOEC) differentiated at the air–liquid interface (ALI) were stimulated with 250 nmol/L cortisol for 1 or 3 weeks. Subsequently, they were assessed for morphology, bioelectrical properties, and gene expression related to oviduct function, glucocorticoid pathway, cortisol metabolism, inflammation, and apoptosis. Results revealed adverse effects of cortisol on epithelium structure, featured by deciliation, vacuole formation, and multilayering. Additionally, cortisol exposure led to an increase in transepithelial potential difference, downregulated mRNA expression of the major glucocorticoid receptor (NR3C1), upregulated the expression of cortisol-responsive genes (FKBP5, TSC22D3), and significant downregulation of oviductal glycoprotein 1 (OVGP1) and steroid receptors PGR and ESR1. The systematic comparison to a similar experiment previously performed by us in porcine oviduct epithelial cells, indicated that bovine cultures were more susceptible to elevated cortisol levels than porcine. The distinct responses between both species are likely linked to their divergence in the cortisol-induced expression changes of HSD11B2, an enzyme controlling the cellular capacity to metabolise cortisol. These findings provide insights into the species-specific reactions and reproductive consequences triggered by maternal stress.

PSIII-29 Evaluating the efficacy of bioelectrical impedance analysis using machine learning models for the classification of parasitized goats

Abstract Rapid identification and evaluation of animal health condition is one of the most important concerns when it comes to livestock productivity, particularly for small ruminants susceptible to infection from blood-feeding gastrointestinal nematodes, like Haemonchus contortus. The present study was designed to optimize the process of differentiating parasite infected goats from healthy goats. This study used male intact Spanish goats (n = 65), aiming to establish a proof of concept for the efficacy of bioelectrical impedance, specifically through the metrics of Resistance, and Reactance, in identifying the health status of goats. The research involved the development and comparative analysis of seven machine learning (ML) models, divided into four classification-based models and three regression models, to assess their capabilities in accurately classifying goats based on bioelectrical properties. The data for this study were gathered from live animals using CQR 3.0 (Sea food analytics), with measurements taken from both ear and tail ends to ensure comprehensive and reliable bioelectrical readings. Among the classification models evaluated, the Random Forest Classification model emerged as the most effective, demonstrating a validation accuracy of 71.8% and a testing accuracy of 77.1%. This was closely followed by the K-NN Classification model, which showed a promising testing accuracy of 86.7%. Conversely, the Support Vector Machines and Boosting Classification models displayed decreased accuracies, indicating variability in the performance of classification models in this context. The regression models, evaluated through metrics such as Mean Squared Error (MSE) and R-square, revealed the K-NN Regression model as the most proficient, with the least Test MSE of 0.13 and an R-square of 0.482. This suggests a moderate correlation and predictive capability in determining the health status of goats based on bioelectrical impedance measurements. The Decision Tree Regression and Support Vector Regressor models showed varying degrees of effectiveness, with the latter indicating a minimal R-square value, highlighting the challenges in applying regression models to this domain. The conducted proof of concept research not only underscores the potential of bioelectrical impedance analysis in veterinary diagnostics, but also opens avenues for further refinement of ML algorithms in classifying and predicting the health status of farm animals. The outcomes of this study could significantly influence management strategies for small ruminants, offering a non-invasive, rapid, and potentially cost-effective tool for early detection of parasitism, thereby enhancing animal welfare and productivity in the agricultural sector.

Identification of Distinct, Quantitative Pattern Classes from Emergent Tissue-Scale hiPSC Bioelectric Properties.

Bioelectric signals possess the ability to robustly control and manipulate patterning during embryogenesis and tissue-level regeneration. Endogenous local and global electric fields function as a spatial 'pre-pattern', controlling cell fates and tissue-scale anatomical boundaries; however, the mechanisms facilitating these robust multiscale outcomes are poorly characterized. Computational modeling addresses the need to predict in vitro patterning behavior and further elucidate the roles of cellular bioelectric signaling components in patterning outcomes. Here, we modified a previously designed image pattern recognition algorithm to distinguish unique spatial features of simulated non-excitable bioelectric patterns under distinct cell culture conditions. This algorithm was applied to comparisons between simulated patterns and experimental microscopy images of membrane potential (Vmem) across cultured human iPSC colonies. Furthermore, we extended the prediction to a novel co-culture condition in which cell sub-populations possessing different ionic fluxes were simulated; the defining spatial features were recapitulated in vitro with genetically modified colonies. These results collectively inform strategies for modeling multiscale spatial characteristics that emerge in multicellular systems, characterizing the molecular contributions to heterogeneity of membrane potential in non-excitable cells, and enabling downstream engineered bioelectrical tissue design.

Active biointegrated living electronics for managing inflammation.

Seamless interfaces between electronic devices and biological tissues stand to revolutionize disease diagnosis and treatment. However, biological and biomechanical disparities between synthetic materials and living tissues present challenges at bioelectrical signal transduction interfaces. We introduce the active biointegrated living electronics (ABLE) platform, encompassing capabilities across the biogenic, biomechanical, and bioelectrical properties simultaneously. The living biointerface, comprising a bioelectronics layout and a Staphylococcus epidermidis-laden hydrogel composite, enables multimodal signal transduction at the microbial-mammalian nexus. The extracellular components of the living hydrogels, prepared through thermal release of naturally occurring amylose polymer chains, are viscoelastic, capable of sustaining the bacteria with high viability. Through electrophysiological recordings and wireless probing of skin electrical impedance, body temperature, and humidity, ABLE monitors microbial-driven intervention in psoriasis.

Electrophysiological Mechanisms and Validation of Ferritin-Based Magnetogenetics for Remote Control of Neurons.

Magnetogenetics was developed to remotely control genetically targeted neurons. A variant of magnetogenetics uses magnetic fields to activate transient receptor potential vanilloid (TRPV) channels when coupled with ferritin. Stimulation with static or RF magnetic fields of neurons expressing these channels induces Ca2+ transients and modulates behavior. However, the validity of ferritin-based magnetogenetics has been questioned due to controversies surrounding the underlying mechanisms and deficits in reproducibility. Here, we validated the magnetogenetic approach Ferritin-iron Redistribution to Ion Channels (FeRIC) using electrophysiological (Ephys) and imaging techniques. Previously, interference from RF stimulation rendered patch-clamp recordings inaccessible for magnetogenetics. We solved this limitation for FeRIC, and we studied the bioelectrical properties of neurons expressing TRPV4 (nonselective cation channel) and transmembrane member 16A (TMEM16A; chloride-permeable channel) coupled to ferritin (FeRIC channels) under RF stimulation. We used cultured neurons obtained from the rat hippocampus of either sex. We show that RF decreases the membrane resistance (Rm) and depolarizes the membrane potential in neurons expressing TRPV4FeRIC RF does not directly trigger action potential firing but increases the neuronal basal spiking frequency. In neurons expressing TMEM16AFeRIC, RF decreases the Rm, hyperpolarizes the membrane potential, and decreases the spiking frequency. Additionally, we corroborated the previously described biochemical mechanism responsible for RF-induced activation of ferritin-coupled ion channels. We solved an enduring problem for ferritin-based magnetogenetics, obtaining direct Ephys evidence of RF-induced activation of ferritin-coupled ion channels. We found that RF does not yield instantaneous changes in neuronal membrane potentials. Instead, RF produces responses that are long-lasting and moderate, but effective in controlling the bioelectrical properties of neurons.

A self-powered, implantable bone-electronic interface for home-based therapeutic strategy of bone regeneration

Bone traumatic injuries, enduring a prolonged healing process since it involves a series of bio events, becomes gradually challenging with increasing aging population. The integration of a home-based therapy strategy with emerging microelectronic technology holds promise for optimizing the whole long-term healing process of bone defect. Given the bioelectric properties of bone, utilizing biomedical electronics to providing external electric field (EF) is preferred for physical therapy strategies. Our study provides a wireless implantable bone-electronic interface (IBEI) based on ultrasonic-driven battery-free piezoelectric technology. The IBEI without percutaneous leads can effectively complete the process of converting ultrasonic signals into electric signals and finally into biological signals for bone repair. This system is miniatured, battery-free, wireless, controllable, biocomfortable and biosafe with high osteogenic efficiency. For the underlying mechanism, the EF can activate multicellular synergistic osteogenesis and up-regulate the Ca2+/CaMKIIα/CREB signal pathway in osteogenesis effector cells. The IBEI aligns with the future trajectory of home-based medicine, presenting a commendable therapy pattern for doctor-patient collaboration and offering a novel perspective in the realm of physical therapy.

The bioelectric mechanisms of local calcium dynamics in cancer cell proliferation: an extension of the A549 in silico cell model.

Advances in molecular targeting of ion channels may open up new avenues for therapeutic approaches in cancer based on the cells' bioelectric properties. In addition to in-vitro or in-vivo models, in silico models can provide deeper insight into the complex role of electrophysiology in cancer and reveal the impact of altered ion channel expression and the membrane potential on malignant processes. The A549 in silico model is the first computational cancer whole-cell ion current model that simulates the bioelectric mechanisms of the human non-small cell lung cancer cell line A549 during the different phases of the cell cycle. This work extends the existing model with a detailed mathematical description of the store-operated Ca2+ entry (SOCE) and the complex local intracellular calcium dynamics, which significantly affect the entire electrophysiological properties of the cell and regulate cell cycle progression. The initial model was extended by a multicompartmental approach, addressing the heterogenous calcium profile and dynamics in the ER-PM junction provoked by local calcium entry of store-operated calcium channels (SOCs) and uptake by SERCA pumps. Changes of cytosolic calcium levels due to diffusion from the ER-PM junction, release from the ER by RyR channels and IP3 receptors, as well as corresponding PM channels were simulated and the dynamics evaluated based on calcium imaging data. The model parameters were fitted to available data from two published experimental studies, showing the function of CRAC channels and indirectly of IP3R, RyR and PMCA via changes of the cytosolic calcium levels. The proposed calcium description accurately reproduces the dynamics of calcium imaging data and simulates the SOCE mechanisms. In addition, simulations of the combined A549-SOCE model in distinct phases of the cell cycle demonstrate how Ca2+ - dynamics influence responding channels such as KCa, and consequently modulate the membrane potential accordingly. Local calcium distribution and time evolution in microdomains of the cell significantly impact the overall electrophysiological properties and exert control over cell cycle progression. By providing a more profound description, the extended A549-SOCE model represents an important step on the route towards a valid model for oncological research and in silico supported development of novel therapeutic strategies.

Tryptophan Prevents the Development of Non-Alcoholic Fatty Liver Disease.

The main aim of this research is to study the protective effects of tryptophan on the histomorphological and biochemical abnormalities in the liver caused by a high-calorie diet (HCD), as well as its ability to normalize mitochondrial functions in order to prevent the development of non-alcoholic fatty liver disease (NAFLD). The study was conducted in male Wistar rats aged 3 months at the start of the experiment. Control animals (group I) were fed a standard diet. Group II experimental animals were fed a diet with an excess of fat (45%) and carbohydrates (31%) for 12 weeks. Group III experimental animals also received L-tryptophan at a dose of 80 mg/kg body weight in addition to the HCD. The presence of NAFLD, functional activity, physiological regeneration, and the state of the liver parenchyma and connective tissue were assessed using physiological, morphological, histo-morphometric, biochemical, and biophysical research methods. HCD induced the development of NAFLD, which is characterized by an increase in liver weight, hypertrophy of hepatocytes and an increase in the concentration of lipids, cholesterol and triglycerides in liver tissue. Increased alanine aminotransferase activity in the liver of obese rats also confirm hepatocytes damage. Tryptophan added to the diet lowered the severity of NAFLD by reducing fat accumulation and violations of bioelectric properties, and prevented a decrease in mitochondrial ATP synthesis. The addition of tryptophan can have a potential positive effect on the liver, reducing the severity of structural, biochemical, mitochondrial and bioelectric damage caused by HCD.

A bioelectrical phase transition patterns the first vertebrate heartbeats.

A regular heartbeat is essential to vertebrate life. In the mature heart, this function is driven by an anatomically localized pacemaker. By contrast, pacemaking capability is broadly distributed in the early embryonic heart1-3, raising the question of how tissue-scale activity is first established and then maintained during embryonic development. The initial transition of the heart from silent to beating has never been characterized at the timescale of individual electrical events, and the structure in space and time of the early heartbeats remains poorly understood. Using all-optical electrophysiology, we captured the very first heartbeat of a zebrafish and analysed the development of cardiac excitability and conduction around this singular event. The first few beats appeared suddenly, had irregular interbeat intervals, propagated coherently across the primordial heart and emanated from loci that varied between animals and over time. The bioelectrical dynamics were well described by a noisy saddle-node on invariant circle bifurcation with action potential upstroke driven by CaV1.2. Our work shows how gradual and largely asynchronous development of single-cell bioelectrical properties produces a stereotyped and robust tissue-scale transition from quiescence to coordinated beating.

Cancer's unique bioelectric properties: From cells to body-wide networks: Comment on: “The distinguishing electrical properties of cancer cells” by Elisabetta Di Gregorio, Simone Israel, Michael Staelens, Gabriella Tankel, Karthik Shankar, and Jack A. Tuszynski (this issue)

Cancer's unique bioelectric properties: From cells to body-wide networks: Comment on: “The distinguishing electrical properties of cancer cells” by Elisabetta Di Gregorio, Simone Israel, Michael Staelens, Gabriella Tankel, Karthik Shankar, and Jack A. Tuszynski (this issue)

Photobiomodulation effects on cancer cells through modifications of their bioelectric properties: Comment on "The distinguishing electrical properties of cancer cells" by E. di Gregorio, S. Israel, M. Staelens, et al.

Photobiomodulation effects on cancer cells through modifications of their bioelectric properties: Comment on "The distinguishing electrical properties of cancer cells" by E. di Gregorio, S. Israel, M. Staelens, et al.

Simulation of Magnetotargeting of Medicines Based on the Calculation of Permeability of Human Tissues by the Electromagnetic Field

Analysis of studies in the field of targeted delivery of drugs, genes and stem cells showed a low level of accuracy of both applied and practical research in this area. Sufficiently encouraging results were obtained with extracorporeal electromagnetic action on a pharmacological complex with a ferromagnetic nanoparticle. With this approach, it is rather difficult to implement the algorithm for introducing the drug into the topographic region (target organ), since in practice, approaches to the clinical application of drug transport technology, taking into account the physicochemical properties of human body tissues, have not been studied in detail. The available models represent various physical and mathematical approaches that do not take into account the bioelectrical and electrostatic properties of the tissues of the organisms of experimental animals and humans. The creation of algorithms and software simulation of this technology will allow calculating variable frequency variables for magnetotargeting in a human digital phantom, which will reduce time spent at the stage of pilot and clinical trials and in the future will form the applied part of the innovative technology. The article presents the methodology and results of multiphysics and mathematical modeling in the Sim4Life for Science, V7.0 package on the example of calculating the control parameters of the electromagnetic field of the region in the area of normal administration of drugs – the vessels of the forearm.

Nucleoporin Nup358 Downregulation Tunes the Neuronal Excitability in Mouse Cortical Neurons.

Nucleoporins (NUPs) are proteins that comprise the nuclear pore complexes (NPCs). The NPC spans the nuclear envelope of a cell and provides a channel through which RNA and proteins move between the nucleus and the cytoplasm and vice versa. NUP and NPC disruptions have a great impact on the pathophysiology of neurodegenerative diseases (NDDs). Although the downregulation of Nup358 leads to a reduction in the scaffold protein ankyrin-G at the axon initial segment (AIS) of mature neurons, the function of Nup358 in the cytoplasm of neurons remains elusive. To investigate whether Nup358 plays any role in neuronal activity, we downregulated Nup358 in non-pathological mouse cortical neurons and measured their active and passive bioelectrical properties. We identified that Nup358 downregulation is able to produce significant modifications of cell-membrane excitability via voltage-gated sodium channel kinetics. Our findings suggest that Nup358 contributes to neuronal excitability through a functional stabilization of the electrical properties of the neuronal membrane. Hypotheses will be discussed regarding the alteration of this active regulation as putatively occurring in the pathophysiology of NDDs.

A nano-conductive osteogenic hydrogel to locally promote calcium influx for electro-inspired bone defect regeneration

Conductive nano-materials and electrical stimulation (ES) have been recognized as a synergetic therapy for ordinary excitable tissue repair. It is worth noting that hard tissues, such as bone tissue, possess bioelectrical properties as well. However, insufficient attention is paid to the synergetic therapy for bone defect regeneration via conductive biomaterials with ES. Here, a novel nano-conductive hydrogel comprising calcium phosphate-PEDOT:PSS-magnesium titanate-methacrylated alginate (CPM@MA) was synthesized for electro-inspired bone tissue regeneration. The nano-conductive CPM@MA hydrogel has demonstrated excellent electroactivity, biocompatibility, and osteoinductivity. Additionally, it has the potential to enhance cellular functionality by increasing endogenous transforming growth factor-beta1 (TGF-β1) and activating TGF-β/Smad2 signaling pathway. The synergetic therapy could facilitate intracellular calcium enrichment, resulting in a 5.8-fold increase in calcium concentration compared to the control group in the CPM@MA ES + group. The nano-conductive CPM@MA hydrogel with ES could significantly promote electro-inspired bone defect regeneration in vivo, uniquely allowing a full repair of rat femoral defect within 4 weeks histologically and mechanically. These results demonstrate that our synergistic strategy effectively promotes bone restoration, thereby offering potential advancements in the field of electro-inspired hard tissue regeneration using novel nano-materials with ES.