Search Results (102)

Ischemic heart disease remains the leading cause of cardiovascular mortality worldwide. In myocardial infarction (MI), extracellular vesicles (EVs)—particularly small EVs (sEVs)—transport therapeutic cargo such as miR-21-5p, which suppresses apoptosis, and other proteins, lipids, and RNAs that can modulate cell death, inflammation, angiogenesis, and remodeling. This review synthesizes recent mechanistic and preclinical evidence on native and engineered EVs for post-MI repair, mapping therapeutic entry points across the MI timeline (acute injury, inflammation, and healing) and comparing EV sources (stem-cell and non-stem-cell), administration routes, and dosing strategies. We highlight engineering approaches—including surface ligands for cardiac homing, rational cargo loading to enhance potency, and biomaterial depots to prolong myocardial residence—that aim to improve tropism, durability, and efficacy. Manufacturing and analytical considerations are discussed in the context of contemporary guidance, with emphasis on identity, purity, and potency assays, as well as safety, immunogenicity, and pharmacology relevant to cardiac populations. Across small- and large-animal models, EV-based interventions have been associated with reduced infarct/scar burden, enhanced vascularization, and improved ventricular function, with representative preclinical studies reporting approximately 25–45% relative reductions in infarct size in rodent and porcine MI models, despite substantial heterogeneity in EV sources, formulations, and outcome reporting that limits cross-study comparability. We conclude that achieving clinical translation will require standardized cardiac-targeting strategies, validated good manufacturing practice (GMP)-compatible manufacturing platforms, and harmonized potency assays, alongside rigorous, head-to-head preclinical designs, to advance EV-based cardiorepair toward clinical testing. Full article

Background/Objectives: Extracellular vesicles (EVs) are nanosized carriers with high biocompatibility, low immunogenicity, and the ability to cross biological barriers, making them attractive for drug delivery. Despite growing interest, the clinical translation of drug-loaded EVs remains limited. This systematic review aimed to summarize current evidence on EV sources, loading strategies, therapeutic applications, and translational challenges. Methods: Following PRISMA 2020 guidelines, a systematic search was conducted in Embase, PubMed, Reaxys, and Scopus for the period 2020–2025. Eligible studies included original articles on drug-loaded EVs from human, animal, plant, or other sources. Data on EV source, drug type, particle size, loading method, administration route, and therapeutic application were extracted. Clinical trials were identified through ClinicalTrials.gov. Results: A total of 65 studies were included after screening 5316 records, along with two clinical trials. Human mesenchymal stem cell (MSC)-derived EVs were the most frequent source in oncology, while plant-derived EVs predominated in non-oncology applications. Anti-cancer drugs such as doxorubicin, gemcitabine, and docetaxel were most frequently loaded, alongside curcumin, berberine, and atorvastatin. EV sizes generally ranged from 50 to 200 nm, with larger vesicles reported for plant-derived EVs. Intravenous administration predominated, with most studies demonstrating sustained release and enhanced therapeutic efficacy. Passive loading was most common, especially for hydrophobic drugs, whereas active methods such as electroporation and sonication were preferred for hydrophilic cargo. Two clinical trials showed preliminary therapeutic benefits with favorable safety. Conclusions: Drug-loaded EVs represent a promising and versatile drug delivery platform, yet their clinical translation is hindered by variability in isolation and loading methods, production scalability, and safety evaluation. Further standardization and large-scale studies are needed to advance EV-based therapeutics toward clinical use. Full article

A promising approach to advancing sustainable urban mobility is the increased use of light electric vehicles, such as e-cycles and their cargo-carrying variants: e-cargo cycles. These micromobility vehicles fall between e-cycles and conventional vehicles in terms of transport capacity, range, and cost. A key advantage of e-cargo cycles over their non-electrified counterparts is the electric powertrain, which enables them to carry heavier payloads, travel longer distances, and reduce driver fatigue. Since the primary use of e-cargo cycles is urban parchment deliveries, trip efficiency plays a critical role in their effectiveness within urban logistics. This efficiency is influenced by factors such as travel distance, traffic density, and the weight and volume of the delivery payload. While higher delivery capacity generally enhances efficiency, studies have shown that as the drop size increases, the efficiency of e-cargo cycle delivery trips tends to decline. A practical way to address this limitation is the use of cargo attachments, such as trailers. These micromobility solutions are already widely implemented globally and significantly enhance transport capacity. This paper reports the process of designing and testing the control algorithm of an electrical system for an experimental attachment demonstrator that can be used to convert most cycle vehicles into cargo variants. The system integrates two 250 W BLDC hub motors, two 576 Wh lithium-ion batteries, dual load-cell sensing in the coupling element, and an STM32-based controller to provide independent propulsion and synchronization with the leading cycle. The force-based control strategy enables automatic adaptation to varying payloads typically encountered in urban logistics, which is supported by the variable storage volume capable of transporting payloads of up to 200 kg. Full article

Craniofacial bone defects of critical size, caused by trauma, tumors, infections, or congenital maldevelopment, represent a major challenge in plastic and reconstructive surgery. Autologous bone grafting is considered the gold standard, but limitations such as donor site morbidity and limited availability have prompted the development of artificial bone tissue engineering scaffolds. In recent years, bioactive scaffolds have been increasingly utilized in favor of inert biomaterials due to their immunomodulation and osteoinduction capabilities. This review methodically summarizes loading strategies for the functionalization of scaffolds with bioactive components, including cell regulatory factors, drugs, ions, stem cells, exosomes, and components derived from human tissues or cells to promote bone regeneration. The following mechanisms are involved: (1) the polarization of macrophages (M1-M2 transition), (2) the dynamic regulation of bone metabolism, and (3) the coupling of osteogenesis and angiogenesis. This review focuses on innovative delivery systems, such as 3D-printed scaffolds, nanocomposites and so on, that enable spatiotemporal control of bioactive cargo release. These address key challenges, such as infection resistance, vascularization, and mechanical stability in the process of bone regeneration. In addition, the article discusses emerging technologies, including stem cells and exosome-based acellular therapies, which demonstrate potential for personalized bone regeneration. This review integrates immunology, materials science, and clinical needs, providing a roadmap for the design of next-generation bone tissue engineering scaffolds to overcome critical-sized bone defects. Full article

Brain tumors encompass a heterogeneous group of neoplasms, including primary and secondary metastatic lesions, with glioblastoma multiforme (GBM) representing the most aggressive primary malignancy. Despite advancements in surgical resection, radiotherapy, and chemotherapy, the prognosis for GBM remains poor due to its infiltrative nature, tumor heterogeneity and resistance mechanisms. Emerging diagnostic tools, such as liquid biopsies, and therapeutic strategies leveraging extracellular vesicles (EVs) are reshaping the field of neuro-oncology. EVs, lipid bilayer-enclosed particles secreted by cells, carry oncogenic cargo such as microRNAs and molecular chaperones, influencing tumor progression, immune evasion, and therapy resistance. Recent research highlights their potential as biomarkers for early diagnosis and vehicles for targeted drug delivery across the blood–brain barrier (BBB). EV-based nanotherapeutics show promise in improving treatment precision, reducing systemic toxicity, and advancing precision medicine in brain tumor management. However, challenges related to EV heterogeneity, cargo-loading efficiency, and large-scale production must be addressed to fully realize their therapeutic potential. This review explores the multifaceted roles of EVs in brain tumors, emphasizing their diagnostic, prognostic, and therapeutic applications. Full article

Background and Objectives: Neuropsychiatric disorders pose a major global health challenge, marked by high prevalence, limited diagnostic precision, and suboptimal therapeutic outcomes. Current diagnoses remain primarily clinical, lacking objective biomarkers, while many patients experience poor remission rates and frequent relapse. The endocannabinoid system (ECS), a central regulator of synaptic plasticity, neuroinflammation, and stress responses, is increasingly implicated in depression, anxiety, schizophrenia, and neurodegenerative diseases. In parallel, extracellular vesicles (EVs) have emerged as critical mediators of intercellular communication and promising biomarker sources, as they reflect the physiological or pathological status of their cells of origin. This review examines the hypothesis that interactions between ECS signaling and EV-mediated communication form a convergent pathway shaping vulnerability and resilience in neuropsychiatric disorders, with potential implications for biomarker identification and therapeutic innovation. Methods: This hypothesis-driven review was developed using a narrative approach, focusing on the interface between cannabinoids and EVs in neuropsychiatric conditions. Relevant publications were identified through PubMed, Scopus, and Web of Science searches up to September 2025. Results: Emerging evidence indicates a bidirectional relationship between ECS activity and EV biology: endocannabinoids can be loaded into EVs to facilitate intercellular signaling, while phytocannabinoids such as THC and CBD can alter EV release and cargo composition. Conclusions: We propose a hypothesis-driven framework in which the possible interplay between cannabinoids and EVs may stimulate new research and support the development of biomarker-guided, personalized therapeutic strategies for neuropsychiatric disorders. Full article

The current known data on the involvement of the peptidergic systems in breast cancer progression is overwhelmingly vast. Peptidergic systems are useful tools for imaging, diagnosis, prognosis and treatment of breast cancer. These systems play a crucial role in both basic and clinical breast cancer research by enabling the exploration of novel molecular mechanisms, signaling pathways, and the development of effective drug design strategies. Breast cancer cells overexpress peptide receptors; at the same time they are known to interact with peptides that (a) exert an oncogenic action (adrenomedullin 2, endothelin, gastrin-releasing peptide, neurokinin A, neuromedin, neuropeptide Y, neurotensin, substance P, vasoactive intestinal peptide), (b) exert an anticancer action (angiotensin (1–7), ghrelin, peptide YY) or (c) exert dual oncogenic and anticancer effects (adrenomedullin, angiotensin II, bradykinin, corticotropin-releasing factor, β-endorphin, glucagon-like peptide 1, gonadotropin-releasing hormone, kisspeptin, methionine-enkephalin, oxytocin). This indicates that peptides, as well as peptide receptor agonists and antagonists, may serve as antitumor agents due to their diverse actions against breast cancer development, including the inhibition of cell proliferation, migration and invasion, induction of apoptosis, and anti-angiogenesis. Multiple strategies have been developed to combat breast cancer, including peptide receptor silencing; antibodies conjugated to specific signaling proteins; antibodies targeting specific peptide receptors or oncogenic peptides; and the use of peptides or peptide receptor agonists/antagonists loaded with antitumor cargo. Future lines of research are suggested in breast cancer using promising anti-breast-cancer peptide receptor antagonists (HOE-140, exendin (9–39), bosentan, macitentan, PD168,368, CGP71,683A, SR48,692, aprepitant) or agonists (FR190,997, semaglutide, exendin 4, goserelin) mentioned in this review. Peptidergic systems have tremendous anti-breast-cancer clinical potential which must be exploited and developed. Taken together, the available data highlight the enormous promise of translational research into breast cancer and peptidergic systems for the development of effective treatments. A full understanding of the roles played by the peptidergic systems in breast cancer will serve to improve diagnosis and treatment. Full article

Work performed in confined and low-height spaces (NSLH) is relatively common across several industries, yet it has not been adequately addressed from an ergonomic perspective. Such activities require workers to adopt awkward postures, most often with the trunk bent and rotated, while handling loads positioned at varying distances from the body. These conditions lead to rapid fatigue, musculoskeletal strain, and, in the long term, may cause serious health disorders. Traditional ergonomic risk assessment methods, such as REBA, RULA, or QEC, were initially applied in these situations; however, the results were unsatisfactory. Their broad applicability and reliance on calculation tables that incorporate factors irrelevant to NSLH tasks prevent them from providing an accurate evaluation of ergonomic risks in these environments. To overcome these limitations, a new assessment method, RALH (Risk Assessment for Narrow Spaces with Low Height), was developed. The method aims to evaluate ergonomic risks in contexts where workers cannot maintain an upright posture, resulting in significant stress on the spinal column, particularly in the lumbar and cervical regions. The RALH methodology incorporates parameters such as trunk inclination, trunk rotation, load weight, distance between the body and the load, exposure duration, and the worker’s physical fitness. A dedicated software tool, ERGO Agent—RALH, was designed to implement this methodology, providing structured data collection, parameter normalization, and ergonomic risk calculation. Case studies, including distribution agents working inside van cargo compartments, demonstrated that the method produces accurate and objective results. Beyond diagnosis, RALH also supports the development of preventive strategies, such as equipment optimization, task allocation, worker training, and physical conditioning. Overall, the RALH method is a practical tool for improving occupational health and efficiency in NSLH environments, where traditional ergonomic approaches are insufficient. Full article

Injectable hydrogels are adaptable drug delivery systems capable of forming localized depots that align with the anatomical and physiological constraints of administration sites. Their performance depends on both the injection environment and the properties of the therapeutic cargo. Applications span ocular, intra-articular, subcutaneous, intramuscular, tumoral, central nervous system, and mucosal delivery, where hydrogels address challenges of clearance, retention, and compatibility. Beyond bulk depots, particulate hydrogel formats such as microgels and nanogels improve syringeability, modularity, and integration with nanoparticle carriers. Functional versatility arises from stimuli responsiveness, including pH, enzymatic, thermal, redox, and light triggers, and from hybrid designs that integrate multiple cues for precision control. Loading strategies range from passive encapsulation to affinity binding and covalent conjugation, with release governed by diffusion, degradation, and stimuli-modulated kinetics. Translational progress depends on reproducible fabrication, scalable manufacturing, and device integration, while site-dependent constraints and regulatory hurdles remain significant challenges. Full article

Despite advances in modern medicine and increased public awareness, cerebral stroke remains a leading cause of death and long-term disability worldwide. With over 600,000 new cases annually, innovative therapeutic strategies are being explored to enhance recovery outcomes. One promising approach is the use of human stem cell-derived extracellular vesicles (EVs), particularly exosomes, which function as mediators of intercellular communication. EVs have emerged as pivotal mediators of intercellular communication with immense potential in therapeutic applications. This review discusses the pioneering journey of EVs from their biogenesis and molecular cargo loading to their translation into clinical strategies for cerebral ischemic stroke therapy. While direct stem cell transplantation has faced limitations such as immune rejection, tumorigenicity, and short shelf life, human stem cell-derived EVs offer a cell-free alternative with enhanced safety, stability, and functional versatility. Preclinical studies reveal their capacity to modulate inflammation, protect neural tissue, and promote recovery through the transfer of bioactive molecules. Additionally, EVs isolated from biofluids such as blood and cerebrospinal fluid serve as promising biomarkers for stroke severity and prognosis. Despite this promise, several challenges persist—from standardizing isolation techniques and optimizing therapeutic cargo to scaling up production for clinical-grade use. This review critically examines the current understanding of EV biology, highlights the advances in stroke-related applications, and outlines key hurdles that must be addressed to unlock their full therapeutic potential. Full article

Exosomes, naturally derived extracellular vesicles, have emerged as powerful bio-nanocarriers in precision medicine. Their endogenous origin, biocompatibility, and ability to encapsulate and deliver diverse therapeutic payloads position them as transformative tools in drug delivery, gene therapy, and regenerative medicine. This review presents a comprehensive analysis of exosome-based therapeutics across multiple biomedical domains, including cancer, neurological and infectious diseases, immune modulation, and tissue repair. Exosomes derived from stem cells, immune cells, or engineered lines can be loaded with small molecules, RNA, or CRISPR-Cas systems, offering highly specific and low-immunogenic alternatives to viral vectors or synthetic nanoparticles. We explore endogenous and exogenous loading strategies, surface functionalization techniques for targeted delivery, and innovations that allow exosomes to traverse physiological barriers such as the blood–brain barrier. Furthermore, exosomes demonstrate immunomodulatory and regenerative properties in autoimmune and degenerative conditions, with promising roles in skin rejuvenation and cosmeceuticals. Despite their potential, challenges remain in large-scale production, cargo loading efficiency, and regulatory translation. Recent clinical trials and industry efforts underscore the accelerating momentum in this field. Exosomes represent a promising platform in precision medicine, though further standardization and validation are required before widespread clinical use. This review offers critical insights into current technologies, therapeutic mechanisms, and future directions to unlock the full translational potential of exosomes in clinical practice. Full article

Dynamic hydrogels are revolutionizing tumor microenvironment (TME) engineering through their stimuli-responsive adaptability, mechanical tunability, and capacity for multifunctional integration. In addition, they are excellent biomaterials for cancer treatments, including their biomimetic properties and controlled cargo release capability. This review introduces the rational design and principles of dynamic hydrogels for recreating the tumor microenvironment and cancer therapy, including natural/synthetic hydrogels, multi-stimuli responsive hydrogels, and multi-drug loading hydrogels. These designs emphasize their unique roles in overcoming drug resistance, enhancing immunotherapy, and enabling patient-specific models. We highlight breakthroughs such as dual-responsive nanocomposites and microfluidic-integrated 3D platforms while addressing translational hurdles like cytotoxicity and regulatory delays. By proposing strategies to bridge material science with clinical needs, this work positions dynamic hydrogels as pivotal tools for next-generation precision oncology. Full article

With the surge in global maritime trade of new energy vehicles (NEVs), the roll-on/roll-off (Ro-Ro) shipping market faces a severe supply–demand imbalance, pushing shipping rates to persistently high levels. To tackle this challenge, NEV manufacturers and other automakers have begun establishing their own Ro-Ro fleets, creating an urgent need for optimized operational scheduling of these proprietary fleets. Against this context, this study focuses on optimizing the operational scheduling of automakers’ self-owned Ro-Ro fleets. Under the premise of deterministic automobile export transportation demands, a mixed-integer programming model is developed to minimize total fleet operational costs, with decision variables covering vessel port call sequence/selection, port loading and unloading quantities, and voyage speeds. A genetic algorithm is designed to solve the model, and the effectiveness of the proposed approach is validated through a real-world case study. The results demonstrate that the optimization method generates clear, actionable scheduling schemes for self-owned Ro-Ro fleets, effectively helping automakers refine their maritime logistics strategies for proprietary fleets. This study contributes to the field by focusing on automaker-owned Ro-Ro fleets and filling the research gap in cargo-owner-centric scheduling, providing a practical tool for automakers’ overseas logistics operations. Full article

Unmanned Aerial Vehicles (UAVs) have revolutionized various industries due to their adaptability, efficiency, and capability to operate in diverse environments. However, conventional UAV designs face trade-offs between flight endurance and maneuverability. This study explores the design, analysis, and optimization of a biplane quadrotor UAV, integrating the vertical takeoff and landing (VTOL) capabilities of multirotors with the aerodynamic efficiency of fixed-wing aircraft to enhance flight endurance while maintaining high maneuverability. The UAV’s structural design incorporates biplane wings with different NACA airfoil configurations (NACA4415, NACA0015, and NACA0012) to assess their impact on drag reduction, stress distribution, and flight efficiency. Computational Fluid Dynamics (CFD) simulations in ANSYS Fluent 2023 R2 (Canonsburg, PA, USA).reveal that the NACA0012 airfoil achieves the highest drag reduction (75.29%), making it the most aerodynamically efficient option. Finite Element Analysis (FEA) further demonstrates that NACA4415 exhibits the lowest structural stress (95.45% reduction), ensuring greater durability and load distribution. Additionally, a hybrid flight control system, combining Backstepping Control (BSC) and Integral Terminal Sliding Mode Control (ITSMC), is implemented to optimize transition stability and trajectory tracking. The results confirm that the biplane quadrotor UAV significantly outperforms conventional quadcopters in terms of aerodynamic efficiency, structural integrity, and energy consumption, making it a promising solution for surveillance, cargo transport, and long-endurance missions. Future research will focus on material enhancements, real-world flight testing, and adaptive control strategies to further refine UAV performance in practical applications. Full article

Biomimetic nanocarriers, particularly membrane-based systems, have emerged as promising platforms for drug delivery. A thorough understanding of the molecular interactions that govern their assembly, stability, and cargo-loading efficiency is essential for optimizing their design and performance. Equally important are their interactions with biological components such as proteins, lipids, nucleotides, and cells, which significantly influence delivery efficacy. Among various techniques for characterizing these nanocarriers, isothermal titration calorimetry (ITC) has proven to be an invaluable tool to study their molecular interactions. ITC enables direct quantification of key thermodynamic parameters, such as binding affinity, stoichiometry, enthalpy, and entropy changes, without the need for molecular labeling or immobilization. This review highlights the application of ITC in the study of biomimetic nanocarriers, focusing on solid lipid nanoparticles, liposomes, extracellular vesicles, cell-derived vesicles and live cells. For each type of nanocarrier, the ITC applications in specific areas and the resulting information are discussed. For example, ITC was used to characterize drug interaction and protein adsorption for solid nanoparticles. In contrast, many aspects of liposomes were explored by ITC, including membrane solubilization and stabilization, peptide interactions, and macromolecule and protein adsorption. Overall, this review aims to provide a conceptual and practical framework for employing ITC in the investigation of biomimetic nanocarrier systems, facilitating their rational design and improved therapeutic performance. Furthermore, the discussion encourages further development of strategies to increase the application in cell-derived vesicles and live cells. Full article