Search Results (779)

Traumatic injuries to the brain and spinal cord remain among the most challenging conditions in clinical neuroscience due to the complexity of repair mechanisms and the limited regenerative capacity of neural tissues. Nanotechnology has emerged as a transformative field, offering precise diagnostic tools, targeted therapeutic delivery systems, and advanced scaffolding platforms that are capable of overcoming the biological barriers to regeneration. This review summarizes the recent advances in nanoscale diagnostic markers, functionalized nanoparticles for drug delivery, and nanostructured scaffolds designed to modulate the injured microenvironment and support axonal regrowth and remyelination. Emerging evidence indicates that nanotechnology enables real-time, minimally invasive detection of inflammation, oxidative stress, and cellular damage, while improving therapeutic efficacy and reducing systemic side effects through targeted delivery. Electroconductive scaffolds and hybrid strategies that integrate electrical stimulation, gene therapy, and artificial intelligence further expand opportunities for personalized neuroregeneration. Despite these advances, significant challenges remain, including long-term safety, immune compatibility, the scalability of large-scale production, and translational barriers, such as small sample sizes, heterogeneous preclinical models, and limited follow-up in existing studies. Addressing these issues will be critical to realize the full potential of nanotechnology in traumatic brain and spinal cord injury and to accelerate the transition from promising preclinical findings to effective clinical therapies. Full article

Printed flexible materials have garnered considerable attention as next-generation materials for bioelectronic applications, particularly hydrogels and elastomers, owing to their intrinsic softness, tissue-like mechanical compliance, and electrical conductivity. In contrast to conventional fabrication approaches, printing technologies enable precise spatial control, design versatility, and seamless integration with complex biological interfaces. This review provides a comprehensive overview of the progress in printable soft conductive materials, with a particular emphasis on the composition, processing, and functional roles of conductive hydrogels and elastomers. This review first introduces traditional fabrication methods for conductive materials and explains the motivation for using printing techniques. We then introduce two major classes of soft conductive materials, hydrogels and elastomers, and describe their applications in both in vitro systems, such as biosensors and soft stimulators, and in vivo settings, including neural interfaces and implantable devices. Finally, we discuss current challenges and propose future directions for advancing printed soft bioelectronics toward clinical translation. Full article

Background: Knee osteoarthritis (KOA) is a degenerative joint disorder marked by cartilage degradation, synovial inflammation, and altered synovial fluid (SF) rheology, resulting in pain and impaired joint function. Intra-articular hyaluronic acid (IA-HA) injections aim to restore SF viscoelasticity and improve lubrication; however, their efficacy may be potentiated when combined with physiotherapy (PT). This monocentric observational study evaluated whether the addition of a multimodal PT program to IA-HA therapy enhances SF rheologic properties compared to IA-HA alone. Methods: A total of 52 patients (aged 47–61) with radiographically confirmed moderate KOA (Kellgren–Lawrence grade 2) were enrolled. Patients were assigned to a pilot group (PG; n = 37) receiving IA-HA (Kombihylan^®, 3 MDa) combined with a multimodal PT protocol, or a control group (CG; n = 15) receiving IA-HA alone. The PT program included ten sessions of transcutaneous electrical nerve stimulation, low-level laser therapy, therapeutic ultrasound, progressive exercise, and cryotherapy. SF samples were collected immediately after the first injection and again at six weeks, then analyzed rheologically using the Kinexus Pro+ rheometer. Viscosity parameters were assessed via steady and oscillatory shear tests. Results: At baseline, both groups demonstrated comparable SF viscosity profiles. After six weeks, the PG exhibited significantly higher shear viscosity values across all measured percentiles and reduced variability in rheological parameters, suggesting a more stable intra-articular milieu. Rheometric analysis indicated enhanced SF viscoelasticity, potentially mediated by reduced inflammation and stimulation of endogenous HA synthesis. In contrast, the CG showed inconsistent viscosity changes, reflecting variable responses to IA-HA monotherapy. Conclusions: Combining IA-HA with multimodal PT significantly improves SF rheological properties in moderate KOA patients compared to IA-HA alone. These findings support the role of mechanical stimulation in enhancing joint lubrication and homeostasis, offering a more consistent and effective approach to viscosupplementation. Full article

Chronic pain is a dynamic, brain-wide condition that eludes effective management by conventional, static treatment approaches. Transcutaneous Electrical Nerve Stimulation (TENS), traditionally perceived as a simple and generic modality, is on the verge of a significant transformation. Guided by advances in brain-state decoding and adaptive algorithms, TENS can evolve into a precision neuromodulation system tailored to individual needs. By integrating multimodal neuroimaging—including the spatial resolution of functional magnetic resonance imaging (fMRI), the temporal sensitivity of an Electroencephalogram (EEG), and the ecological validity of functional near-infrared spectroscopy (fNIRS)—with real-time machine learning, we envision a paradigm shift from fixed stimulation protocols to personalized, closed-loop modulation. This comprehensive review outlines a translational framework to reengineer TENS from an open-loop device into a responsive, intelligent therapeutic platform. We examine the underlying neurophysiological mechanisms, artificial intelligence (AI)-driven infrastructures, and ethical considerations essential for implementing this vision in clinical practice—not only for chronic pain management but also for broader neuroadaptive healthcare applications. Full article

Sea anemone venoms contain diverse toxins that have significant pharmacological potential, including anticancer, ecticidal, and immunotherapeutic properties. However, critically, the extraction methodology influences venom composition and bioactivity. This study characterized venom from Stichodactyla haddoni obtained via homogenization, electrical stimulation, and milking. Extraction yields varied significantly between methods: the homogenization, electrical stimulation, and milking of healthy sea anemones yielded crude venoms at rates of 17.8%, 3.4%, and 1.5%, respectively. SDS-PAGE revealed distinct protein banding patterns and concentrations, while RP-HPLC demonstrated method-dependent compositional differences. Comprehensive proteomic profiling identified 2370 proteins, encompassing both unique and shared components across extraction techniques. Label-free quantitative analysis confirmed significant variations in protein abundance that was attributable to the extraction method. Cytotoxicity assays against cancer cell lines revealed concentration-dependent inhibition, with milking-derived venom exhibiting the highest potency. Insecticidal activity against Tenebrio molitor was also method-dependent, with milking venom inducing the highest mortality rate. These findings elucidate the profound impact of extraction methodology on the protein composition and functional activities of S. haddoni venom, providing crucial insights for its optimized exploitation in pharmacological development. Full article

Low back pain (LBP) remains one of the most prevalent and disabling musculoskeletal conditions globally, with profound social, economic, and healthcare implications. The rising incidence and chronic nature of LBP highlight the need for more objective, personalized, and effective approaches to assessment and rehabilitation. In this context, bioengineering has emerged as a transformative field, offering novel tools and methodologies that enhance the understanding and management of LBP. This narrative review examines current bioengineering applications in both diagnostic and therapeutic domains. For assessment, technologies such as wearable inertial sensors, three-dimensional motion capture systems, surface electromyography, and biomechanical modeling provide real-time, quantitative insights into posture, movement patterns, and muscle activity. On the therapeutic front, innovations including robotic exoskeletons, neuromuscular electrical stimulation, virtual reality-based rehabilitation, and tele-rehabilitation platforms are increasingly being integrated into multimodal treatment protocols. These technologies support precision medicine by tailoring interventions to each patient’s biomechanical and functional profile. Furthermore, the incorporation of artificial intelligence into clinical workflows enables automated data analysis, predictive modeling, and decision support systems, while future directions such as digital twin technology hold promise for personalized simulation and outcome forecasting. While these advancements are promising, further validation in large-scale, real-world settings is required to ensure safety, efficacy, and equitable accessibility. Ultimately, bioengineering provides a multidimensional, data-driven framework that has the potential to significantly improve the assessment, rehabilitation, and overall management of LBP. Full article

Background and Objectives: Facial paralysis involves the complete or partial loss of facial movement due to damage to the facial nerve, leading to impaired voluntary muscle function and facial asymmetry. Given its significant physical and psychosocial impact, there is an urgent need to strengthen the evidence supporting non-pharmacological treatments. This umbrella review aims to compile the most reliable and current data to establish a consensus on the effectiveness of such interventions for patients with facial paralysis. Materials and Methods: This study is an umbrella review. A systematic search was conducted in PubMed, Embase, Scopus, and CINAHL (28 July 2024). The variables assessed included overall healing/recovery rate, facial disability, and facial function. Methodological quality was evaluated using the AMSTAR and ROBIS tools. Screening was performed independently by two reviewers, with a third reviewer resolving any discrepancies. Results: Five systematic reviews were included, all evaluating the impact of non-pharmacological interventions in facial paralysis. The findings suggest that acupuncture and electrical stimulation may improve recovery rates and facial function, although high heterogeneity and methodological limitations were noted in some studies. No definitive conclusions could be drawn regarding facial disability. Conclusions: The combination of electrotherapy with other complementary techniques, such as facial exercises or laser therapy, appears to be a safe and potentially effective approach for facial paralysis rehabilitation. Nonetheless, further research employing standardized protocols and higher methodological quality is necessary to establish more robust conclusions for physiotherapeutic practice. Full article

Electroactive biomaterials are a key emerging technology for the treatment of neural damage. Conducting polymer-coated carbon microfibers are particularly useful for this application because they provide directional support for cell growth and tissue repair and simultaneously allow for ultrasensitive recording and stimulation of neural activity. Here, we report in vitro experiments investigating the biology of Schwann cells (SCs), a major player in peripheral nerve regeneration, on electroconducting microfibers. The optimal molecular composition of the cell substrate and cell culture medium was studied for SCs dissociated from rat and pig peripheral nerves. The substrate molecules were then attached to carbon microfibers coated with poly (3,4-ethylenedioxythiophene) doped with poly [(4-styrenesulfonic acid)-co-(maleic acid)] (PCMFs), which served as an electroactive scaffold for culturing nerve explants. Biphasic electrical stimulation (ES) was applied through the microfibers, and its effects on cell proliferation and migration were assessed in different cell culture media. Rodent and porcine SCs avidly migrated on PCMFs functionalized with a complex of poly-L-lysine, heparin, basic fibroblast growth factor, and fibronectin. Serum and forskolin/heregulin increased, by two-fold and four-fold, the number of SCs on PCMFs, respectively, and ES further doubled cell numbers without favoring fibroblast proliferation. ES additionally increased SC migration. These results provide a baseline for using biofunctionalized PCMFs in peripheral nerve repair. Full article

Cystic fibrosis is a multisystem disorder caused by mutations in the CFTR gene that lead to impaired ion and fluid transport across secretory epithelia. Although the therapeutic impact of CFTR modulators has been extensively studied in airway epithelia, their efficacy in extra-pulmonary tissues, such as the pancreas, has been less explored. This study evaluated the effects of the CFTR modulators, VX770 (ivacaftor), VX661 (tezacaftor), and VX445 (elexacaftor), administered either individually or in combination, on CFPAC-1 cells, a pancreatic ductal epithelial cell line derived from a cystic fibrosis patient harboring the F508del CFTR mutation. The cells were cultured and differentiated onto porous supports, and a panel of functional parameters was assessed. These included transepithelial electrical conductance, fluid reabsorption, apical surface fluid pH, protein concentration, and microviscosity, the latter analyzed with multiple particle tracking. To simulate a pro-inflammatory micro-environment, the cells were preconditioned with lipopolysaccharide (LPS). Treatment with VX661 and VX445 resulted in significant improvement in epithelial function, with the triple combination producing the most pronounced rescue. Pro-inflammatory stimulation by LPS increased the production of cytokine IL6, IL-8, and IL-1β, as well as the protein content of the apical surface fluid. Despite the LPS pro-inflammatory stimulus, CFTR modulators preserved or slightly enhanced their efficacy in restoring CFTR-mediated ion and fluid transport. However, they did not reduce cytokine expression under pro-inflammatory conditions. Collectively, these findings show that CFTR modulators can restore critical aspects of cystic fibrosis pancreatic epithelial physiology in vitro, even under pro-inflammatory stress, supporting their potential relevance beyond the airway disease. Full article

A wearable closed-loop transcutaneous electrical nerve stimulation (TENS) platform has been developed to address the limitations of conventional open-loop neuromodulation systems. Unlike existing systems such as CLoSES—which targets intracranial stimulation—and electromyography-triggered functional electrical stimulation (EMG-FES) platforms primarily used for motor rehabilitation, the proposed device uniquely integrates low-latency surface electromyography (sEMG)-driven control with six-channel current stimulation in a fully wearable, non-invasive format aimed at ambulatory pain modulation. The system combines real-time sEMG acquisition, adaptive signal processing, a programmable multi-channel stimulation engine, and a high-voltage, boost-regulated power supply within a compact, battery-powered architecture. Bench-top evaluations demonstrate rapid response to EMG events and stable biphasic output (±22 mA) across all channels with high electrical isolation. A human-subject protocol using the Cold Pressor Test (CPT), heart rate variability (HRV), and galvanic skin response (GSR) has been designed to evaluate analgesic efficacy. While institutional review board (IRB) approval is pending, the system establishes a robust foundation for future personalized, mobile neuromodulation therapies. Full article

Neuromuscular electrical stimulation (NMES) has been shown to improve motor activities and daily living. Prior studies indicated extracellular vesicles (EVs) play a role in cellular communication. Here, we evaluated transcriptomic profiles of tibialis muscle, brain, and plasma-derived EVs following NMES in wild type (WT) and Klotho heterozygous (Kl^HET) mice. Muscle RNA-seq data demonstrated that, in both genotypes, the most upregulated functional categories were related to glucose metabolism and response to insulin, with pathways uniquely affected in each genotype. There was a similarity of the non-coding RNA transcriptome of plasma EVs, with functional patterns suggesting response to oxygen and insulin and long-term synaptic potentiation. The brain transcriptome showed little functional overlap between WT and Kl^HET mice. In WT, brain upregulation of genes was related to blood flow and cell adhesion processes, while Kl^HET showed upregulation of immune function. The results indicate that similar metabolic function is impacted in the location of stimulation, but the distal impact of stimulation on the brain is associated with Klotho deficiency. Full article

By sensing changes in the contact force between the leg and level ground, humans can perceive their walking speed and adjust leg stiffness to accommodate walking terrains. To realize this natural regulation mechanism on the lower limb amputee, noninvasive functional electrical stimulation (nFES) was used to assist the subject in sensing the change in contact force between the leg and level ground, allowing for the adjustment of control parameters in the prosthetic leg. The cost function was designed to combine the tracking errors of the joints and changes in the stimulating current. For different walking terrains, an extremum-seeking control (ESC) method was employed to search for suitable control parameters in real time by monitoring the changes in the cost function. The stability of the proposed controller with extremum-seeking dynamics was demonstrated. The experimental results demonstrated that the extremum-seeking method effectively adjusted the control parameters of the prosthetic leg in response to changes in the cost function. Full article

Objective: Dysphagia is common among elderly patients after hip fracture surgery and can lead to aspiration pneumonia, malnutrition, and delayed rehabilitation. This study aims to present current clinical practice patterns of assessment and intervention for dysphagia in this patient group. Methods: The study was conducted through a two-round online questionnaire targeting Danish occupational therapists with expertise in dysphagia post hip fracture. Results: A total of 71 therapists participated in round one, and 44 (62%) completed round two. Triggers for assessment included coughing, recurrent pneumonia, voice changes, altered eating habits, unplanned weight loss, functional decline, and comorbidities; age was rarely used. Frequently used assessment tools were Facio-Oral Tract Therapy (57.1%), the Minimal Eating Observation Form—Version II (40%) and the Volume–Viscosity Swallow Test (41.4%). Key interventions included texture modification, posture correction, patient education, oral hygiene optimization, compensatory strategies, and dysphagia training; oral screens and electrical stimulation were less common. Conclusions: This study provides a descriptive overview of current dysphagia assessment triggers, tools, and interventions used for elderly hip fracture patients in Denmark. The findings highlight clinical practice patterns that can inform future research on patient outcomes and the effectiveness of specific interventions in this population. Full article

Brain organoid technology has revolutionized in vitro modeling of human neurodevelopment and disease, providing unprecedented insights into cortical patterning, neural circuit assembly, and pathogenic mechanisms of neurological disorders. Critically, human brain organoids uniquely recapitulate human-specific developmental processes—such as the expansion of outer radial glia and neuromelanin—that are absent in rodent models, making them indispensable for studying human brain evolution and dysfunction. However, a major bottleneck persists: Extended culture periods (≥6 months) are empirically required to achieve late-stage maturation markers like synaptic refinement, functional network plasticity, and gliogenesis. Yet prolonged conventional 3D culture exacerbates metabolic stress, hypoxia-induced necrosis, and microenvironmental instability, leading to asynchronous tissue maturation—electrophysiologically active superficial layers juxtaposed with degenerating cores. This immaturity/heterogeneity severely limits their utility in modeling adult-onset disorders (e.g., Alzheimer’s disease) and high-fidelity drug screening, as organoids fail to recapitulate postnatal transcriptional signatures or neurovascular interactions without bioengineering interventions. We summarize emerging strategies to decouple maturation milestones from rigid temporal frameworks, emphasizing the synergistic integration of chronological optimization (e.g., vascularized co-cultures) and active bioengineering accelerators (e.g., electrical stimulation and microfluidics). By bridging biological timelines with scalable engineering, this review charts a roadmap to generate translationally relevant, functionally mature brain organoids. Full article

A wide range of strategies have been developed to modulate dysfunctional brain activities. This narrative review provides a comparative analysis of biophysical, genetic, and biological neuromodulation approaches with an emphasis on their known or unknown molecular targets and translational potential. The review incorporates data from both preclinical and clinical studies covering deep brain stimulation, transcranial electrical and magnetic stimulation, focused ultrasound, chemogenetics, optogenetics, magnetogenetics, and toxin-based neuromodulation. Each method was assessed based on specificity, safety, reversibility, and mechanistic clarity. Biophysical methods are widely used in clinical practice but often rely on empirical outcomes due to undefined molecular targets. Genetic tools offer cell-type precision in experimental systems but face translational barriers related to delivery and safety. Biological agents, such as botulinum neurotoxins, provide long-lasting yet reversible inhibition via well-characterized molecular pathways. However, they require stereotaxic injections and remain invasive. To overcome individual limitations and improve targeting, delivery, and efficacy, there is a growing interest in the synthesis of multiple approaches. This review highlights a critical gap in the mechanistic understanding of commonly used methods. Addressing this gap by identifying molecular targets may help to improve therapeutic precision. This concise review could be valuable for researchers looking to enter the evolving field of the neuromodulation of brain function. Full article