Endogenous neuroprotection in vascular cognitive impairment and dementia.

Opportunities for the future of transcranial magnetic stimulation and epilepsy.

Endogenous electric fields (EFs) are essential for tissue regeneration but are diminished under hyperglycemia conditions, thereby impeding diabetic wound healing. Here, we report a biodegradable, glucose-powered electronic fabric bandage (GEB) that restores wound-edge electrical fields and enables closed-loop wound healing. To avoid compromising clinical applicability, we integrated all components into a soft, lightweight, and breathable bandage design to replace the traditional bulky electrical stimulator design. We also show the universal glucose-powered electricity generation and therapeutic functions of the electronic bandage across species and organs in diabetic wound models. In diabetic mouse wounds, porcine skin defects, and intestinal injury, the bandage uses endogenous glucose for power generation, thereby reducing local glucose levels and restoring the endogenous EF that guided cell migration, reprogrammed macrophage polarization, and promoted angiogenesis, to accelerate wound healing. These findings should establish an “endogenous glucose-powered symbiotic bioelectronics” paradigm for next-generation bioelectronic medicine.

Drug discovery has long treated the brain as a passive target or a site of symptom control, not as a regulatory organ that drives systemic therapeutic responses. Discrete neural circuits directly and measurably control immune activation, inflammatory signaling, metabolic regulation, hormone release, and cardiovascular function. This evidence is substantial. Its therapeutic potential remains largely untapped. This article introduces Neuro-Regulatory Drug Discovery (NRGDD), a formalized drug-discovery framework that organizes and operationalizes principles drawn from neuroimmunology, bioelectronic medicine, autonomic pharmacology, and systems pharmacology into a causally structured development logic. While individual elements of this approach exist within established fields, no prior framework has combined circuit-specific eligibility criteria, causal disruption requirements, peripheral biomarker validation standards, and regulatory development strategy within a unified discovery model. NRGDD is distinguished from adjacent fields not by the novelty of its biological substrate but by the specificity and enforceability of its operational requirements. Under NRGDD, therapeutic activity is initiated through a defined neural circuit and confirmed through measurable changes in peripheral biomarkers. The framework specifies criteria for circuit selection, causal proof, biomarker validation, and regulatory strategy. The core hypothesis is that drugs or devices targeting specific neural regulatory circuits will produce consistent, measurable downstream changes in peripheral biomarkers. These changes can guide drug development, reduce clinical failures, and support effects that persist beyond the dosing period. Device-based neuromodulation is primarily used to identify and validate druggable circuits, not as the primary therapeutic goal. Clinical support comes from vagus nerve stimulation (VNS) trials in rheumatoid arthritis (RA), pyridostigmine treatment in COVID-19, and nicotine patch therapy in ulcerative colitis.

Organic electrochemical transistors (OECTs) are emerging as powerful platforms for neural sensing, bridging the gap between ionic signaling in biological tissue and electronic readout. Their volumetric ionic-electronic coupling, high transconductance, low-voltage operation, and mechanical compliance enable faithful amplification of weak neural signals while minimizing tissue mismatch. OECTs achieve multifunctional interfacing by amplifying weak signals and simultaneously monitoring electrophysiological and neurochemical activity through their soft, ion-mediated operation, extending beyond conventional electrode approaches. Recent advances in materials, including conducting polymers, organic semiconductors, and hybrid systems, expand the performance and versatility of OECT channels and gates. Device innovations such as horizontal, vertical, and fiber-based architectures further tailor OECTs to cortical, deep-brain, and peripheral applications. Integration strategies emphasize flexible and stretchable platforms, chronic and bioresorbable implants, multiplexed arrays for large-scale mapping, and closed-loop systems that unify sensing, processing, and stimulation. Despite significant progress, challenges remain in achieving long-term stability, scalable fabrication, and clinical translation. Continued innovation in materials, device architectures, and system-level integration is expected to transform OECTs into versatile platforms for next-generation neural interfaces and bioelectronic medicine.

Vagus nerve stimulation (VNS) is an established neuromodulatory therapy approved for epilepsy, depression, obesity, stroke rehabilitation, rheumatoid arthritis, migraine, and cluster headaches. Its therapeutic potential has expanded dramatically, with growing evidence supporting its efficacy across a wide spectrum of neurological, psychiatric, cardiovascular, immunological, metabolic, and gastrointestinal disorders. Despite this progress, the field has lacked a comprehensive synthesis that unifies mechanistic insights with translational applications across organ systems. This review addresses that gap by systematically integrating current knowledge in the multifactorial mechanisms through which VNS modulates central and peripheral functions, including neuromodulator release, synaptic plasticity, autonomic regulation, neuroimmune control, and endocrine integration. In addition, this review identifies key limitations of VNS, including biological heterogeneity, technical constraints, and methodological variability, and proposes future innovations such as selective fiber targeting, closed-loop systems, and artificial intelligence-guided personalization. By providing a rigorous, system-level overview of VNS mechanisms and their translational relevance, this article serves as a foundational resource for advancing the science and clinical deployment and helping illustrate future directions for precision neuromodulation and bioelectronic medicine.

Towards energy autonomy in bio-electronic medicine: a comprehensive review of laser-based optical wireless power transfer evolution

The transition of bioelectronic medicine to clinical use is currently limited by a lack of non-invasive sensors capable of measuring autonomic tone during active neuromodulation. Conventional monitoring modalities, such as mean arterial pressure (MAP) and Ag/AgCl chest electrodes, are often invasive, cumbersome, or susceptible to motion artifacts. Here, we present a novel framework employing an in-ear sensor (AURIS) to continuously monitor heart rate variability (HRV) during therapeutic neuromodulation. These sensors utilize a polydimethylsiloxane (PDMS) substrate to ensure biocompatibility and superior conformability. Experiments in a rodent model (n = 3) demonstrate that the AURIS platform achieves gold-standard fidelity, with mean heart rate differences of 6.03 BPM and mean RR interval deltas of 3.18 ms compared to chest electrodes. Sensor agreement was statistically validated using independent t-tests, showing no significant difference between modalities (all p > 0.46). While time-domain shifts trended toward significance, complexity metrics showed robust sequential responses with large effect sizes, including the SD1/SD2 ratio (d = 1.474) and the DFA α ratio (d = 1.091). These findings validate a sensor architecture that is durable, accessible, and provides the necessary technical foundation for closed-loop feedback and non-invasive clinical trials.

Bioelectronic medicine in the rehabilitation of diseases: Opportunities and challenges

Self-powered bioelectronic medicine targeting the gut-kidney axis via low-level vagus nerve stimulation mitigates kidney damage

Peripheral nerve interfaces play a central role in bioelectronic medicine. Since the early foundational experiments of Luigi Galvani in the 1770s, there have been over 250 years of development in electrical neuromodulation. Even so, current clinical approaches to interface with peripheral nerves are limited. Bioelectronic interfaces for small, branched nerves are of increasing interest to unlock new therapies and minimize off-target effects. This is facilitated by our growing understanding of peripheral nervous system physiology and advances in new materials and technologies. Therefore, this review examines historical and recent developments in FDA-approved peripheral nerve interfaces and investigational interfaces with an emphasis on approaches to target smaller nerves. Unmet needs in small nerve peripheral nerve interfaces are highlighted, followed by an examination of new strategies being pursued to address them. To conclude, ongoing challenges are summarized, revealing opportunities and prospects for future advancements.

The Sixth Bioelectronic Medicine Summit took place on March 4 and 5, 2025 at the Garden City Hotel in New York, and was co-hosted by the Feinstein Institutes for Medical Research (FIMR), Northwell Health and the University of Minnesota. The Summit brought together speakers and attendees from academia, medicine and industry to discuss the evolving landscape of neuromodulation and bioelectronic therapeutics. This year’s Summit was titled “Neurotechnologies for Individuals and Communities” and emphasized approaches that consider differences between subjects to deliver precision neuromodulation therapies, as well as approaches that expand the therapeutic footprint of neuromodulation to underserved populations and communities. The Summit included sessions covering basic and translational research, device development and commercialization, and emerging clinical applications. This meeting report summarizes the major events from the two days of the Summit, including keynote addresses, scientific sessions, discussion panels, award presentations, and sponsored talks.

Abstract Piezoelectric materials have become a research hotspot in bioelectronic medicine due to their excellent electromechanical conversion properties. In particular, biodegradable piezoelectric materials can avoid the risk of secondary removal surgeries, revealing great potential in clinical applications. This review summarizes the types, mechanisms, and properties of representative degradable piezoelectric materials, including amino acids, peptides, polysaccharides, and synthetic polymers. The processing strategies and the progress of their application in biomedical applications are further demonstrated. Finally, challenges and perspectives of the development of degradable piezoelectric materials are also discussed.

ABSTRACT Bioelectronic medicine has provided innovative approaches to regulate cellular function, but a major limitation of most bioelectronic therapies is their dependence on external power sources such as batteries. Wearable thermoelectric generators with the ability to harvest sustainable energy from body heat represent a promising solution. Here, we present a device, called “integrated grid of generators imparting thermoelectric energy” (IGNITE), that enables wearable, sustainable, self‐powered modulation of insulin secretion via bioelectric stimulation of engineered human cells. The IGNITE system continuously harvests body heat and converts it into a controlled electrical output to drive insulin release. The wearable system consists of an 8 × 8 series generator array composed of P‐type (Sb 2 Te 3 @PEDOT:PSS) and N‐type (Bi 2 Te 3 @TCNQ) materials, which efficiently generates and amplifies electrical energy to produce a stable 4.2 V output through an integrated voltage regulation circuit. A 60 s electrical stimulation induces reactive oxygen species (ROS)‐mediated activation of engineered mammalian cells, leading to insulin production in a controlled and reproducible manner. In a proof‐of‐concept experiment in type 1 diabetic mice, the system achieved glycemic regulation without any external power source. This device lays the foundation for next‐generation bioelectronic therapies by integrating sustainable bioenergy energy harvesting, nanotechnology, and cellular engineering for endocrine modulation.

Achieving robust adhesion and seamless electrical integration between hydrogels and biological tissues remains a formidable challenge in tissue engineering and bioelectronics. Herein, we report a photothermal-mediated bioadhesion strategy for atraumatic yet tough tissue adhesion and an integrated electrical interface. By molecularly engineering functionalized polyaniline derivatives as bridging polymers, we achieved photothermally controlled tissue penetration, enabling the spontaneous formation of covalent-topological interactions between tissue and hydrogel. In contrast to conventional bioadhesives that depend primarily on surface interactions, our strategy employs tissue-penetrating conducting polymers to form a three-dimensional interlocking network. This integrated system forms highly efficient electrical pathways across the tissue-hydrogel interface, significantly reducing interfacial impedance and enabling effective interfacial electrical integration. Through in vitro and in vivo validation, we demonstrate the strategy's dual capability for high-precision electrophysiological monitoring and electrocoupling therapy in myocardial infarction. This bioadhesion strategy offers a simple and universal paradigm for bioelectronic and regenerative medicine.

Electrical stimulation has expanded beyond excitable tissues, with bioelectronic medicine exploring new therapeutic avenues. We propose a novel paradigm: continuously repeated electroporation to induce controlled Ca2+ influx and modulate cellular functions. Given the central role of Ca2+ as a second messenger tightly regulated by homeostatic mechanisms, transient permeabilization via electric fields enables perturbation of intracellular Ca2+ dynamics, influencing processes such as proliferation, differentiation, metabolism, and cell death. We define "MILD electroporation" as a process involving prolonged or repetitive mild membrane permeabilization induced by electric fields that facilitates calcium entry without causing direct cell death. At 5th World Congress on Electroporation and Pulsed Electric Fields in Biology, Medicine, and Food & Environmental Technologies, we presented in vitro evidence showing that specific electric field waveforms elicit Ca2+ oscillations in stem cells, modulating gene expression and promoting proliferation. We also presented preliminary results suggesting that burst-modulated alternating fields may slow cancer cell proliferation.

Recent research highlights the potential of ultrasound (US) stimulation as a noninvasive tool for modulating neural and cellular signaling in the spleen and liver to treat inflammatory diseases and diabetes. However, challenges like nerve activation failures, off-target stimulation, and organ motion during respiration can affect treatment efficacy. This study introduces a novel tracking framework for accurate liver and spleen motion tracking using US imaging to overcome these challenges. The tracking framework integrates an enhanced Kanade-Lucas-Tomasi (EKLT) tracker with a long short-term memory (LSTM) predictor. The EKLT tracker provides precise annotations that improve LSTM training, while the LSTM compensates for occlusions and noise by making predictions based on prior data and dynamically adjusting the region of interest (ROI). Spleen motion tracking was evaluated using 40 recordings from 10 participants, each undergoing four distinct breathing patterns. Additionally, the method was evaluated on a liver motion dataset from MICCAI, collected from 9 subjects. Spleen tracking was most accurate during slow, shallow breathing, with an average error of 0.4 $\pm$ 0.4 mm, and had an average error of 1.37 $\pm$ 0.9 mm during fast, deep breathing. Liver tracking results showed high accuracy with an average error of 0.3 $\pm$ 0.2 mm. The EKLT-LSTM framework offers advantages over previous tracking models, providing high accuracy in tracking liver and spleen motion under occlusion and noisy conditions. The EKLT-LSTM is suitable for end-organ modulation applications and can be adapted to other ultrasound-guided therapies and bioelectronic medicine.

Abstract Organic electrochemical transistors (OECTs) are increasingly recognized as high‐performance, flexible platforms for bioelectronics, owing to their ultra‐low voltage operation, high transconductance, and biocompatibility. The integration of gels, such as hydrogels and ionogels, with robust 3D polymer networks has progressed from traditional solid‐state electrolytes to functional gate and semiconducting gel channels, with mobility exceeding 1 cm 2 V −1 s −1 , transconductance over 80 mS, and stretchability surpassing 100%. This enables the development of inherently flexible, stretchable OECTs with mechanical resilience, high transconductance, and dynamic functionality. Despite the significant progress, challenges remain in understanding hydrogel properties and interfaces for synergistic optimization of device performance and scaling up fabrication. This review provides a systematic overview of gel‐based OECTs, and discusses the gel design strategies with their performance trade‐offs. Hydrogels and ionogels are then compared across various device components, highlighting their gel optimization and different strengths. Significant device engineering strategies for optimizing gel‐based OECTs, such as material enhancements and structural innovations, are discussed, alongside emerging applications in wearable health monitoring, bioelectronic medicine, biomimetic electronics, and environmental sensing. The review concludes by summarizing the current research landscape, identifying persistent challenges, and outlining potential solutions for the development of gel‐based OECTs.

Wireless cellular stimulation has been widely applied for bioengineering and bidirectional communication with the brain. Different technologies, such as photoelectrical stimulation as an alternative to optogenetics, have emerged for a wide range of remote therapeutic applications using light. Metasurfaces enable pixel-wise control of electric field distribution by engineering absorption and wavefront shaping, with responses tuned to incident light polarization, frequency, and phase, offering precise stimulation and wireless control in retinal, cochlear, and cardiac implants. Moreover, by leveraging terahertz (THz) band patches, reconfigurable metasurfaces controlled via FPGA and holography, and virtual reality-assisted designs, these interfaces can revolutionize bioelectronic medicine.

Acupuncture electroceuticals: The convergence of traditional acupuncture theory and modern bioelectronic medicine