Given current clinical interest in vagus nerve stimulation (VNS), there are surprisingly few studies characterizing the anatomy of the vagus nerve in large animal models as it pertains to on-and off-target engagement of local fibers. We sought to address this gap by evaluating vagal anatomy in the pig, whose vagus nerve organization and size approximates the human vagus nerve. Here we combined microdissection, histology, and immunohistochemistry to provide data on key features across the cervical vagus nerve in a swine model, and compare our results to other animal models (mouse, rat, dog, non-human primate) and humans. In a swine model we quantified the nerve diameter, number and diameter of fascicles, and distance of fascicles from the epineural surface where stimulating electrodes are placed. We also characterized the relative locations of the superior and recurrent laryngeal branches of the vagus nerve that have been implicated in therapy limiting side effects with common electrode placement. We identified key variants across the cohort that may be important for VNS with respect to changing sympathetic/parasympathetic tone, such as cross-connections to the sympathetic trunk. We discovered that cell bodies of pseudo-unipolar cells aggregate together to form a very distinct grouping within the nodose ganglion. This distinct grouping gives rise to a larger number of smaller fascicles as one moves caudally down the vagus nerve. This often leads to a distinct bimodal organization, or 'vagotopy'. This vagotopy was supported by immunohistochemistry where approximately half of the fascicles were immunoreactive for choline acetyltransferase, and reactive fascicles were generally grouped in one half of the nerve. The vagotopy observed via histology may be advantageous to exploit in design of electrodes/stimulation paradigms. We also placed our data in context of historic and recent histology spanning multiple models, thus providing a comprehensive resource to understand similarities and differences across species.

Since the 1940s electrocorticography (ECoG) devices and, more recently, in the last decade, micro-electrocorticography (µECoG) cortical electrode arrays were used for a wide set of experimental and clinical applications, such as epilepsy localization and brain–computer interface (BCI) technologies. Miniaturized implantable µECoG devices have the advantage of providing greater-density neural signal acquisition and stimulation capabilities in a minimally invasive fashion. An increased spatial resolution of the µECoG array will be useful for greater specificity diagnosis and treatment of neuronal diseases and the advancement of basic neuroscience and BCI research. In this review, recent achievements of ECoG and µECoG are discussed. The electrode configurations and varying material choices used to design µECoG arrays are discussed, including advantages and disadvantages of µECoG technology compared to electroencephalography (EEG), ECoG, and intracortical electrode arrays. Electrode materials that are the primary focus include platinum, iridium oxide, poly(3,4-ethylenedioxythiophene) (PEDOT), indium tin oxide (ITO), and graphene. We discuss the biological immune response to µECoG devices compared to other electrode array types, the role of µECoG in clinical pathology, and brain–computer interface technology. The information presented in this review will be helpful to understand the current status, organize available knowledge, and guide future clinical and research applications of µECoG technologies.

Bone regeneration is a complex biological process that involves the coordinated action of osteoblasts, osteoclasts, and mesenchymal stem cells (MSCs). While bone possesses an intrinsic ability to heal, large defects, delayed unions, and non-unions require advanced therapeutic interventions. Electrical stimulation (ES) has emerged as a promising strategy to enhance bone healing by modulating cellular activity, promoting osteogenic differentiation, and accelerating vascularization. This review explores the mechanistic role of bioelectrical cues in bone regeneration, emphasizing the influence of voltage-gated ion channels, particularly voltage-gated calcium channels (VGCCs), in transducing electrical signals into biochemical responses. Various types of ES modalities, including direct current (DC), capacitive coupling (CC), Pulsed Electromagnetic Field (PEMF), and piezoelectric stimulation, are evaluated for their effectiveness in clinical and preclinical applications. Additionally, the synergistic potential of ES when combined with biomaterials, stem cells, and growth factors is discussed. Despite promising results, challenges remain in translating preclinical findings to clinical applications, with key hurdles including standardization of treatment protocols, variability in patient responses, and regulatory constraints. Large-animal models have provided insights into the efficacy of ES-based therapies, but limitations in field penetration and treatment reproducibility hinder widespread adoption. Future advancements in bioelectronic medicine, smart scaffolds, and artificial intelligence (AI)-driven personalized therapies hold potential to optimize ES-based bone regeneration. Addressing current limitations through interdisciplinary research will be critical in establishing ES as a mainstream therapeutic approach in orthopedic and maxillofacial regenerative medicine. Graphical Abstract