Search Results (8,340)

The development of biocompatible materials has gained traction due to the increasing clinical demands for customizable and functional medical devices. Chitosan, a deacetylated derivative of chitin, is a naturally occurring biopolymer with strong antimicrobial properties, immunocompatibility, and structural adaptability, making it a promising candidate for biomedical applications. Through mechanisms such as crosslinking, ionic bonding, gas formation, and UV radiation, the mechanical properties and stimulus responses of chitosan-based hydrogels can be tailored for drug delivery at specific sites or under specific pH, light, or electrical conditions. Beyond drug delivery, chitosan hydrogels have shown considerable potential for vascular tissue repair. The porous structure of chitosan allows patient specific vascular scaffolding to be created that promotes the recovery rate veins and stenting procedures. Thermally sensitive hydrogels can deliver drugs to target regions to further assist in vascular healing. Furthermore, recent developments with composite polymers and coatings engineered to self-assemble within veins provide scaffolds for vascular tissue growth. This manuscript reviews chitosan hydrogel fabrication methods and their corresponding materials properties, with particular emphasis on drug delivery to vascular tissues. Furthermore, relevant findings from clinical trials are summarized to support the potential of chitosan hydrogels for future clinical use. Challenges of chitosan hydrogels, such as insufficient mechanical strength, high degradation rates, and complex manufacturing, remain as areas for research break-through. Full article

Asthma is defined as a chronic airway inflammatory disorder with over-activation of the immune system accompanied by the inability to resolve inflammation. SPMs are novel potent lipid mediators that play an important role in maintaining inflammation homeostasis and macrophages’ functional plasticity. This review will look into the potential function of SPM-programmed macrophage reprogramming as a novel therapeutic strategy for asthma. Unlike current anti-inflammatory treatments, which only focus on suppressing inflammation, SPMs can actively drive the inflammation resolution phase by promoting efferocytosis and wound healing while maintaining the defense against infection. In experimental asthma animal models, lipoxins, resolvins, protectins, and maresins have been demonstrated to alleviate inflammation and airway hyperresponsiveness, shift macrophages towards pro-resolving phenotypes and thus facilitate the resolution process. Levels of some SPM subclasses were found to be reduced in severe or uncontrolled asthmatics, indicating defective resolution pathways may contribute to asthma persistence. The mechanisms include down-regulation of pro-inflammatory cytokines, alteration of macrophage phenotype, improvement of immune homeostasis in the airway milieu, etc. These molecules have become highly promising therapeutic agents after the development of metabolically stable analogs, receptor-targeted agonists, and an improved delivery system. Multi-omics studies coupled with patient stratification based on biomarkers will potentially help in the future to develop personalized resolution-based therapy, in particular for those steroid-resistant and non-type 2 asthmatics. Nevertheless, the evidence provided so far is mainly preclinical; more challenges in terms of pharmacokinetics, formulation and formulation development, regulatory agency approval, and clinical validation remain and will be overcome through further studies, thus warranting investigation into SPM-mediated strategies for asthma and other chronic inflammatory diseases. Full article

Bacterial infections pose a serious threat to human health, and antibiotics remain the first-line therapeutic agents in clinical practice. However, the vast majority of antibiotics lack the ability to penetrate cell membranes, which severely limits the number of clinically available options for treating intracellular bacterial infections. Developing efficient intracellular antibiotic delivery strategies is therefore of considerable clinical significance, both for reducing antibiotic dosage and for expanding the repertoire of drugs applicable to intracellular infections. To address this challenge, we constructed a protein-based delivery platform mediated by a cell-penetrating miniprotein for efficient intracellular antibiotic delivery. In this system, bovine serum albumin (BSA), which possesses broad antibiotic-binding capability, was employed as the drug carrier, while the cell-penetrating miniprotein ZF5.3, which is capable of endosomal escape, served as the transmembrane delivery mediator. ZF5.3 was conjugated to BSA via a bioorthogonal reaction, and ceftriaxone (CRO) was selected as the model antibiotic to construct a nanoscale delivery system. The binding interaction between CRO and BSA was characterized using UV-Vis, HPLC, and molecular docking techniques. The assembly of the ZF5.3–BSA delivery platform was confirmed by UV-Vis absorption spectroscopy and gel electrophoresis. Intracellular delivery efficiency was evaluated by confocal fluorescence imaging and flow cytometry, and the results demonstrated that ZF5.3 conjugation enhanced intracellular protein delivery efficiency by over 5-fold. Fluorescence co-localization analysis revealed that ZF5.3-mediated cargo is mainly distributed in the cytoplasm and does not completely co-localize with lysosomal markers, suggesting its ability to effectively escape from lysosomes. An intracellular infection model using Staphylococcus aureus was established. Colony-forming unit (CFU) counting experiments confirmed that the delivery system significantly enhanced the intracellular antibacterial activity of ceftriaxone. CCK8 cytotoxicity assays confirmed that the system is non-toxic to cells. Full article

Gold nanoparticles (AuNPs) have emerged as versatile antiviral nanoplatforms because their size, morphology, plasmonic properties, and surface chemistry can be precisely engineered. In this review, we summarize the core design principles of antiviral AuNPs from a structure–function–mechanism perspective. We first outline representative synthetic and interface-programming routes for AuNP preparation, including citrate reduction, Brust–Schiffrin synthesis, seed-mediated growth, green synthesis, direct thiol-conjugation, and mixed-ligand shell strategies, emphasizing how these approaches define particle size, morphology, surface accessibility, interfacial composition, and downstream biofunctionalization potential. We then discuss major surface engineering strategies, including polyethylene glycol, nucleic acids, antibodies and nanobodies, peptides, glycans, antiviral drugs, and biomimetic coatings, with particular attention to how ligand density, orientation, flexibility, and interfacial stability determine biological performance. Next, we examine how functionalized AuNPs inhibit different stages of the viral life cycle, including viral attachment and entry, intracellular replication, assembly and egress, photothermal inactivation, and immune modulation or vaccine delivery. Finally, we highlight current challenges, including incomplete structure–activity relationships, dynamic nano–bio interactions under physiological conditions, limited standardization across studies, and translational barriers related to safety, reproducibility, and scale-up. This review provides a conceptual framework for the rational development of next-generation AuNP-based antiviral nanotherapeutics. Full article

Ex vivo liver perfusion (EVLP) sustains human or large animal livers outside the body under near-physiological conditions, enabling functional monitoring for lactate clearance, bile production, and oxygen consumption and allowing targeted therapeutic interventions. Originally developed to optimize donor grafts for transplantation, EVLP has evolved into a powerful translational research platform bridging preclinical discovery and early clinical translation. This review discusses EVLP as a platform for gene therapy, immunotherapy, pharmacology, and personalized medicine, with particular emphasis on gene- and immune-based interventions as mechanistically mature exemplars. We consolidate advances in pharmacological testing and toxicity modeling, viral and non-viral gene delivery, genome engineering, and immunomodulation using perfused livers. We further describe emerging applications, including autologous EVLP pathways for organ-confined therapy, ex vivo liver surgery, and bioengineering strategies such as biliary organoid repair, RNA interference, and mitochondrial transfer. We highlight how these applications align with a paradigm shift in biomedical research, including the NIH’s recent initiative to prioritize human-based experimental models over animal-only studies. By leveraging transplant-declined or surgically resected organs that would otherwise be unused, ex vivo perfusion bridges the gap between pre-clinical testing and clinical practice, enabling real-time evaluation of interventions in functional human tissue. We discuss both the scientific opportunities afforded by EVLP and the technical, biosafety, and ethical challenges that must be addressed to enable responsible clinical translation. Full article

Background/Objectives: Automated insulin delivery (AID) systems have improved the management of type 1 diabetes (T1D), but exercise and nutrition remain challenging because they rapidly alter glucose flux, substrate oxidation, hepatic glucose output, insulin requirements, and fuel availability. This narrative review aimed to synthesize current evidence on the interaction between AID systems, physical activity, and nutritional strategies from a metabolism-oriented perspective. Methods: A narrative bibliographic approach was used to integrate evidence from clinical trials, observational studies, technical studies, consensus statements, and reviews involving people with T1D across different life stages, including pediatric, adolescent, adult, and pregnancy-related contexts, when available. The review focused on AID systems, exercise physiology, nutritional strategies, meal announcement, bolus adjustment, dual-hormone systems, metabolic biomarkers, and emerging metabolomic approaches. Results: AID systems generally improve time in range and reduce hypoglycemia across several user groups, although most exercise- and nutrition-specific evidence comes from adult and pediatric/adolescent cohorts rather than pregnancy-specific exercise studies. Exercise-related glucose responses remain highly dependent on user input, exercise modality, insulin on board, meal timing, and metabolic state. Planned exercise announcement, prandial bolus reduction before postprandial activity, and individualized carbohydrate intake remain key strategies. Biomarkers such as lactate, ketone bodies, non-esterified fatty acids, and counter-regulatory hormones may help explain interindividual variability and support future personalization. Conclusions: Nutrition and exercise management in AID users should be interpreted as a dynamic metabolic interface among exogenous insulin, endogenous counter-regulation, substrate availability, and algorithmic control. Emerging approaches, including activity sensors, adaptive algorithms, dual-hormone systems, digital twins, and metabolomics-informed personalization, may improve safety and reduce user burden, but several remain exploratory and require further validation in diverse free-living conditions. Full article

Traditional mineral drugs represent an underexploited reservoir of natural antitumor agents; however, their clinical translation has historically been hindered by poor bioavailability, non-specific biodistribution, and dose-limiting toxicity. This review comprehensively examines the pharmacological mechanisms and modern formulation strategies driving the renaissance of mineral-based oncology therapeutics. We highlight how mineral drugs exert potent anticancer effects through interconnected pathways, including regulated cell death (e.g., apoptosis, ferroptosis), cell-cycle arrest, and immunomodulation. Crucially, we evaluate recent advances in drug delivery systems, such as liposomes, polymeric nanoparticles, inorganic frameworks, and stimuli-responsive (e.g., pH, redox, enzyme) release systems that successfully overcome traditional pharmacological barriers. These bioengineering strategies not only improve solubility and tumor targeting but also significantly widen the therapeutic window, as evidenced by enhanced tumor suppression and reduced systemic toxicity in preclinical models. Despite this progress, challenges regarding in vivo chemical transformations and tumor heterogeneity remain. Ultimately, we propose a closed-loop “Composition–Mechanism–Delivery” design paradigm to guide future research, facilitating the translation of ethnopharmacological heritage into precision mineral-based therapeutics. Full article

Artificial intelligence (AI) is increasingly applied to healthcare decision-making; however, many persistent patient safety risks arise from sociotechnical conditions such as communication breakdowns, coordination failures, and organisational culture rather than diagnostic or decision error alone. While simulation can engage these dimensions of care, AI-supported simulation remains limited by heterogeneity and a lack of explicit conceptual structure. This study presents a narrative and conceptual review of the healthcare simulation and AI literature to identify structural barriers to coherent AI reasoning about simulation. Drawing on this synthesis, we introduce Transformative Simulation (TfS) as an intentional framework that can be formalised as an ontology for AI-supported simulation focused on cultural and systems-level change. TfS structures simulation through explicit Simulation-Based Intentions, an aligned design–delivery–data–debrief process, and foundational considerations of purpose, perspective, power, preparation, and possibility. Framed in this way, TfS enables AI systems to interpret simulation artefacts in relation to declared intent, sociotechnical context, and ethical boundaries. We further describe an Intentionality–Simulation–Intelligence triad and a continuous learning loop that align human values, simulation structure, and AI reasoning. The findings of this review suggest that an important challenge in applying AI to healthcare simulation may be ontological as well as technical, and that explicit representation of intention and context is necessary to support coherent, context-sensitive, and system-aligned AI reasoning in healthcare. Full article

Background/Objectives: The aim of current study was the significant improvement of both the flowability and the compressibility of mesoporous silica microparticles (MSMs), to enable the formulation a potential drug delivery system. MSMs are of emerging interest in the pharmaceutical industry, due to their numerous advantages and versatile applicability, such as improvement in aqueous solubility and epithelial permeability, thus enhancing the oral bioavailability of drugs. However, the formulation of these types of materials has been a major challenge. This problem originates from poor powder flow characteristics due to particle properties. Methods: A binder-free high-shear wet granulation (HSWG) process was performed to improve the flowability and compressibility of the model material, meanwhile preserving its porosity. The prepared granules were characterized by particle size, size distribution, yield percentage, particle morphology, porosity, powder flowability, crushing strength, and stability. Micro-CT measurements were performed to examine the structure of the granules and to see the internal segmentation resulted by the two-step granulation process. The granules were compressed into tablets to evaluate the compressibility behavior based on the models of Kawakita and Walker. The physical parameters of the compressed tablets, such as breaking hardness, tensile strength, and thickness, were tested. Results: The prepared granules were evaluated successfully according to the mentioned properties and found to be satisfactory compared to the raw materials. The binder-free method appeared to be effective, thus the use of binders may be avoided if the process is designed well and critical process parameters (CPPs) selected carefully. The granules showed good stability over a one-year testing period. The micro-CT test also verified the success of the initial concept of preparing core–shell structured granules, and enabled the determination of macropores. Nevertheless, the results were completed with BET measurements to determine specific surface area of the granules. Conclusions: The effect of the critical process parameters of the granulation process on all the mentioned attributes was investigated and since major differences were observed between the batches, the effect of the selected CPPs were also verified. Full article

Theranostics is a novel approach that integrates diagnostic and therapeutic efficacy on a single platform, holding great promise for precision medicine by enabling real-time monitoring of disease progression and therapeutic response. Despite significant advances, the successful development and delivery of theranostic systems are critically limited by multiple biological barriers present at systemic, tissue, cellular, anatomical, and immunological levels. These barriers restrict bioavailability, target accessibility, and therapeutic efficacy, while often increasing off-target accumulation and adverse effects. This review provides a comprehensive overview of the major biological barriers encountered in theranostic development, including physiological barriers such as plasma protein binding, renal clearance, and hepatic metabolism; anatomical barriers like endothelial linings, the blood–brain barrier (BBB), and the tumor microenvironment; cellular barriers involving membrane permeability, intracellular trafficking, and endo-lysosomal entrapment; and immunological barriers such as immune recognition, inflammatory responses, and complement activation. Special emphasis is placed on the BBB, highlighting its structural complexity, transport mechanisms, and strategies such as molecular Trojan-horse technology, receptor-mediated and adsorptive-mediated transcytosis, and nanocarrier-based approaches to enhance central nervous system delivery. The review further discusses targeted delivery challenges, including receptor heterogeneity and multidrug resistance, and critically evaluates current strategies to overcome these barriers through surface functionalization, stimuli-responsive systems, biomimetic carriers, and controlled-release mechanisms. Finally, recent advances, clinical challenges, and future perspectives—including personalized theranostics, artificial intelligence—assisted design, and next-generation barrier-penetrating systems—are explored. Overall, this review aims to provide a structured understanding of biological barriers in theranostics and highlight innovative approaches to improve their translational potential. Full article

Background: Effective strategies for delivering neuroprotective agents to the brain remain a major challenge due to the poor solubility, rapid metabolism, and low bioavailability of promising molecules, such as 7,8-dihydroxyflavone (7,8-DHF). This small-molecule TrkB receptor agonist exhibits significant antioxidant, neuroprotective properties, and additional effects on metabolic regulation, but its therapeutic potential is limited by unfavorable pharmacokinetic characteristics. Nanotechnology-based delivery systems are increasingly explored to improve drug stability, enhance bioavailability, and facilitate direct nose-to-brain transport following intranasal administration. In this study, lipid nanoparticles encapsulating 7,8-DHF were developed using a fish-oil-based lipid core enriched with ω-3 polyunsaturated fatty acids (DHA and EPA) and naturally derived excipients, including soybean lecithin and ε-polylysine. Methods: The formulation was optimized using a Design of Experiments (DoE) approach based on a 2³ full factorial design, evaluating drug concentration, lecithin concentration, and surfactant type (Pluronic^® F127 or Tween^® 80). The main formulation responses considered were particle size, polydispersity index (PDI), zeta potential, and encapsulation efficiency. Results: The optimized nanoparticles exhibited nanometric dimensions (<250 nm); spherical morphology, confirmed by TEM; low polydispersity (PDI < 0.3); and adequate encapsulation efficiency. Stability studies in simulated biological fluids indicated good physicochemical stability for up to 48 h, while interaction studies with mucin suggested a good interaction within the mucus environment. ROS scavenging capacity was confirmed through the DPPH chemical assay, and in vitro experiments on olfactory ensheathing cells, selected as a biologically relevant model for their anatomical localization along the olfactory pathway, showed reduced cytotoxicity of the encapsulated drug compared with the free form. Conclusions: Collectively, these results support the potential application of the developed nanoformulation in the intranasal delivery of 7,8-DHF. Full article

Bone defects from trauma, tumour resection, infection, and degenerative disease remain a major clinical burden, and autografts face limitations of supply and donor-site morbidity. Three-dimensional (3D) printing offers a route to patient-specific, architecturally defined bone scaffolds, while biopolymers from natural sources provide biodegradability, biocompatibility, and extracellular matrix-mimicking cues consistent with sustainable, green biomaterials science. This review synthesises recent progress in 3D printing of biopolymer-based scaffolds for bone tissue engineering. We first examine the principal feedstocks—alginate, gelatin and gelatin methacryloyl, collagen, chitosan, silk fibroin, cellulose, and microbial polyesters—and their preparation, crosslinking chemistry, and printability. We then compare extrusion, light-based, and indirect printing technologies and the process–property relationships governing resolution, mechanical competence, and cell viability. Composite and functionalisation strategies, including biopolymer–bioceramic hybrids and controlled delivery of growth factors and antimicrobial agents, are analysed as routes to osteoinduction, vascularisation, and infection control. Finally, we evaluate translational performance in preclinical models and outline central challenges of vascularisation, mechanical–degradation matching, scalability, and regulatory standardisation. Biopolymer 3D printing is positioned as a ve rsatile, sustainable platform whose clinical maturation depends on integrated material, structural, and biological design. Full article

Background: The mucosal barrier presents a significant challenge for non-invasive delivery of macromolecular therapeutics, often requiring administration with poor bioavailability and increased toxicity risks. The polymeric immunoglobulin receptor (pIgR) contains an extracellular secretory component (SC) for immunoglobulin binding and a membrane-anchored stem domain capable of apical-to-basolateral transcytosis. We hypothesized that targeting the stem domain could enable active drug transport across mucosal barriers. Methods: Using phage display, we identified four high-affinity nanobodies against human and murine pIgR. Two lead candidates (3LTHMP-4 and 3LTHMP-5) demonstrated efficient apical-to-basolateral transport in vitro (Transwell assays) and in vivo (fluorescence imaging). Engineered bispecific antibodies fusing these nanobodies with anti-IL-5 mAb reslizumab were administered via inhalation in a murine asthma model at one-tenth the intraperitoneal reslizumab dose. Resluts: The bispecific antibodies showed significant therapeutic efficacy, while reslizumab alone at equivalent concentrations failed to demonstrate efficacy. Hydrogen–Deuterium Exchange Mass Spectrometry (HDX-MS) revealed that both 3LTHMP-4 and 3LTHMP-5 specifically bind to the pIgR stem domain (residues 578–612), a region distinct from the dimeric IgA binding site. Conclusions: These findings suggest that stem domain-specific binding may facilitate transport across the mucosal barrier while preserving native receptor physiology, offering a potential strategy for effective transmucosal delivery of biologics. Full article

Fatty acid-binding protein 7 (FABP7) is a multifunctional lipid chaperone that is enriched in radial glia and astrocytes within the central nervous system (CNS) and is frequently upregulated in glioma. Beyond its established roles in glial development, lipid homeostasis, and circadian regulation, growing evidence positions FABP7 at the intersection of tumor metabolism, neuronal activity, and immune modulation in the brain. In this review, we integrate the physiological functions of FABP7 in glial cells with its tumor-intrinsic and microenvironmental roles in glioma. We summarize how gliomas co-opt FABP7-dependent metabolic, transcriptional, and post-transcriptional programs to promote stemness, lipid remodeling (e.g., altered fatty acid composition, lipid droplet formation, and lipid peroxidation resistance), inflammatory signaling, and invasive growth, including nuclear FABP7-mediated transcriptional activation linked to oncogene status. Furthermore, we discuss the role of FABP7 in shaping the tumor–neuro–immune interface, including regulating immunosuppressive gene networks, pro-tumoral macrophage polarization, resistance to T-cell-induced ferroptosis and immunotherapy, and tumor microtube-mediated integration into neuronal circuits to support glioma progression. Finally, we highlight therapeutic opportunities and challenges, including small-molecule FABP7 inhibitors, brain-directed delivery strategies, chronotherapeutic considerations, and combination approaches with immunotherapy. Collectively, this work positions FABP7-centered metabolic, circadian, and neuro-immune networks as potential vulnerabilities in glioma, linking fundamental glial biology to glioma therapeutics. Full article

Cancer remains one of the leading causes of morbidity and mortality worldwide, with lung, breast, and colorectal cancers among the most prevalent and lethal malignancies. In recent years, extracellular vesicles (EVs) have emerged as important mediators of intercellular communication and promising tools in oncology. EVs are membrane-bound vesicles released by most cell types and carry diverse biomolecules, including nucleic acids, proteins, lipids, and metabolites derived from their parent cells. Their presence in biological fluids makes them attractive candidates for liquid biopsy applications and minimally invasive cancer diagnosis. In addition, EVs have gained considerable attention as therapeutic platforms due to their biocompatibility, stability, and ability to deliver functional cargo to recipient cells. Beyond mammalian EVs, plant-derived extracellular vesicles (PDEVs) are increasingly being investigated as scalable and potentially safe nanocarriers for biomedical applications. This review summarizes current advances in the use of EVs for cancer diagnosis and therapy, with particular emphasis on their role as biomarkers, drug-delivery systems, and emerging therapeutic agents. Furthermore, the review discusses current challenges and future perspectives related to EV isolation, characterization, and clinical translation in oncology. Full article