Search Results (1,803)

Because lesions associated with digestive system diseases are often deeply seated, embedded within complex luminal milieus, and protected by substantial local delivery barriers, conventional diagnostic and therapeutic modalities remain constrained in their targeting capability, minimal invasiveness, and precision. Microrobots, leveraging micro-scale motion, active navigation, programmable controllability, and theranostic integration, open a new avenue for the precise diagnosis and treatment of digestive system diseases. Here, we review the major actuation modalities and structural designs of microrobots and discuss recent advances in their use across the gastrointestinal and hepatopancreatobiliary systems, focusing on targeted drug delivery, biospecimen harvesting, lesion detection, and interventional treatment. We further discuss the major obstacles to progress in this field, including robust operation in complex in vivo settings, real-time imaging and closed-loop feedback control, biosafety, degradability, and eventual clinical implementation. With continued advances in high-performance materials, multimodal actuation, intelligent control, and convergence with endoscopic and medical imaging technologies, microrobots are poised to accelerate the transition of digestive disease care toward precision, intelligence, and minimally invasive intervention. Full article

Background/Objectives: The blood–brain barrier (BBB) remains a major obstacle to effective gene therapy for neurological disorders by limiting delivery of viral vectors, nanoparticles, and biologics to the central nervous system. Multiple strategies have been developed to transiently disrupt or bypass the BBB, including focused ultrasound (FUS) with microbubbles, osmotic agents, biochemical modulators, and receptor-mediated transport systems. Among these approaches, FUS-mediated BBB opening has emerged as the most spatially precise and clinically advanced strategy. Methods: This narrative review synthesizes recent preclinical and clinical literature on BBB microdisruption technologies for central nervous system gene therapy, with primary emphasis on FUS combined with microbubbles. We review BBB physiology, gene delivery platforms, the development of FUS technologies, optimization parameters, and translational evidence across neurological diseases from animal models through early-phase human studies. Results: FUS-mediated BBB opening has emerged as the leading method for transient barrier modulation. Preclinical studies in Parkinson’s disease, Alzheimer’s disease, Huntington’s disease, glioblastoma, amyotrophic lateral sclerosis, and lysosomal storage disorders demonstrate enhanced gene delivery, increased transgene expression, and improved functional outcomes. Large-animal studies and early clinical trials indicate that BBB opening is reversible, spatially controlled, and generally well tolerated. Clinical investigations have demonstrated successful delivery of therapeutic agents across neurological indications, with preliminary efficacy signals including improved drug penetration, metabolic changes, and potential survival benefits. Optimization of acoustic parameters, microbubble characteristics, and real-time cavitation monitoring remains critical for maximizing safety and therapeutic efficacy. Conclusions: BBB microdisruption, particularly through FUS with microbubbles, represents a transformative platform for central nervous system gene therapy. Continued research is needed to standardize treatment protocols, characterize long-term safety, and facilitate broader clinical translation. Full article

Immune cells possess an intrinsic covalent signalling system in which endogenous electrophilic species function as molecular regulators of cellular state that integrate metabolic activity, oxidative stress, and inflammatory signals. Lipid peroxidation-derived electrophiles, enzymatically generated electrophilic lipid mediators, nitro-fatty acids, and metabolite-derived electrophiles selectively modify reactive amino acid residues within signalling proteins to regulate immune cell differentiation, metabolic adaptation, stress responses, and tissue responses. This perspective highlights that endogenous electrophilic signalling provides a biological blueprint for the development of next-generation precision covalent immunotherapeutics. Beyond exploiting electrophilic chemistry as a reactive pharmacological strategy, emerging insights reveal that immune cells naturally employ regulated covalent modifications to achieve stimulus-dependent control of signalling networks. Advances in chemoproteomics, structural biology, systems immunology, computational chemistry, and targeted delivery technologies are enabling the identification of electrophile-sensitive regulatory targets and the rational design of selective covalent modulators. The discussion includes how the principles derived from endogenous electrophilic signalling can guide therapeutic innovation across major immunotherapeutic areas, including chronic inflammatory diseases, cancer immunology, inflammasome-driven disorders, fibrotic disease, neuroinflammation, and vascular immunometabolic disorders. By translating endogenous covalent regulatory mechanisms into precision drug design strategies, electrophile-guided pharmacology offers an emerging strategy for developing therapies that reprogramme immune cell states, restore immune homeostasis, and achieve stimulus-dependent modulation of disease-associated immune responses. Full article

Background/Objectives: Nanotechnology has become a transformative area in modern dentistry, providing new opportunities for better diagnosis, targeted drug delivery, improved restorative materials, antimicrobial treatments, and tissue regeneration. This scoping review outlines the scope, key developments, and future directions of nanotechnology use across all dental specialties, highlights emerging innovations, and identifies major translational challenges and research priorities. Methods: This review followed the Joanna Briggs Institute (JBI) methodology for scoping reviews and adhered to the PRISMA-ScR guidelines. These guidelines, originally by Arksey and O’Malley (2005) and later updated by Levac et al. (2010) and Peters et al. (2020, 2021), guided the process. The Population, Concept, and Context (PCC) framework guided the eligibility criteria. Included studies were primary research or reviews reporting nanotechnology applications in any dental specialty, published in English, with no date restriction. Excluded were non-peer-reviewed sources, conference abstracts without full text, studies unrelated to dental applications, and non-English publications. A comprehensive literature search was conducted across PubMed/MEDLINE, Scopus, and Web of Science. After screening titles and abstracts and reviewing full texts, 133 studies were included. Results: The included studies covered a wide range of fields such as restorative dentistry, implantology, periodontology, endodontics, drug delivery, tissue regeneration, oral diagnostics, antimicrobial applications, prosthodontics, orthodontics, and emerging technologies like nanorobotics and graphene-based systems. The most commonly reported nanomaterials were silver nanoparticles (AgNPs), calcium phosphate nanoparticles (CaP NPs), and polymeric nanoparticles such as PLGA and chitosan. Additionally, there was a notable increase in publications starting from 2019. Conclusions: Nanotechnology offers transformative possibilities in every area of dentistry. Nonetheless, challenges such as nanotoxicology safety, regulatory alignment, and effective clinical application need resolution. Essential steps include standardized characterization, gathering long-term safety data, and establishing international regulatory standards to ensure safe adoption of nano dentistry. Full article

Circadian rhythms regulate key biological processes central to cancer biology, including cell cycle control, DNA repair, metabolism, immune function, and drug pharmacokinetics. Experimental models consistently demonstrate marked time-of-day differences in the efficacy and toxicity of chemotherapy, targeted agents, and immunotherapies. Clinical studies of chronomodulated chemotherapy—particularly with fluoropyrimidines, platinum compounds, and anthracyclines—show reproducible reductions in treatment-related toxicity, while effects on survival outcomes remain variable and often sex dependent. Emerging clinical evidence also suggests that timing of immune checkpoint inhibitor administration may influence progression-free and overall survival across several tumor types. However, translation into routine oncology practice has been limited by interindividual variability in circadian phase, tumor-specific disruption of clock function, lack of validated biomarkers, and logistical constraints of time-specific drug delivery. Advances in circadian phenotyping, wearable monitoring, and adaptive dosing technologies now offer feasible pathways toward individualized, biology-driven treatment timing. This narrative review critically evaluates mechanistic, preclinical, and clinical evidence for chronotherapy across oncological treatment modalities and examines challenges and opportunities for its integration into precision cancer care. Full article

Background: Acute myeloid leukemia (AML) is a heterogeneous and aggressive hematologic malignancy, and LY-11h is a novel acylhydrazide-based histone deacetylase inhibitor with promising therapeutic potential for AML. However, its poor aqueous solubility, limited intestinal dissolution, and narrow therapeutic window hinder oral formulation development and motivate the development of dosage forms with flexible dose-design capabilities. Herein, an integrated hot-melt extrusion (HME)–fused deposition modeling (FDM) strategy was developed to convert LY-11h into printable amorphous solid dispersion (ASD) dosage forms. Methods: HPMC-AS was used as a pH-responsive carrier to enhance intestinal release while restricting premature gastric release, and HPC-EF was incorporated to improve filament processability. Single-factor and DoE studies identified critical formulation and process variables and established formulation–process–property relationships, while machine learning further modeled nonlinear interactions and guided optimization. In-line near-infrared spectroscopy combined with polarized light microscopy enabled real-time monitoring of LY-11h amorphization and melt homogenization during HME. Results: ExtraTrees and Bagging models showed promising predictive performance for key filament properties, and PAT-stage validation confirmed strong agreement with experimental values. The 15 DoE-designed ASD filaments were successfully fabricated into FDM-printed tablets with reproducible geometry. Equilibrium-solubility and in vitro dissolution studies demonstrated enhanced intestinal-pH solubility and reproducible pH-responsive release. Conclusions: Collectively, these findings establish a technological proof of concept for the manufacture of LY-11h dosage forms with adjustable formulation and geometric attributes. Further in vivo pharmacokinetic studies are required to determine whether these manufacturing capabilities translate into predictable dose–exposure relationships and individualized dose control. Full article

Aerosol jet printing, AJP, has emerged as a versatile direct ink writing technology enabling high-resolution, non-contact patterning of diverse biomaterials across a broad viscosity range. This capability facilitates the fabrication of complex micro- and mesoscale architectures on planar and non-planar substrates, advancing applications in biosensing, microfluidics, tissue engineering, and drug delivery fields. Herein, we review the integration of this high-resolution, rapid prototyping method with bioinks, including proteins, DNA, collagen, gelatin, and silk fibroin, and analyze how processing parameters influence structural and functional outcomes designed for applications for the above mentioned biotechnological fields. The ability by aerosol jet printing to combine structural, electrical, and biological functionalities within single platforms supports the development of multifunctional biomedical devices with higher potential than those produced using other direct ink writing techniques. While challenges such as bioink stability and process scalability, as well as the lack of deeper analyses about the efficiency of real applications of aerosol-jet-printed biotools, still remain open, AJP demonstrates significant promise as an enabling technology for next-generation biofabrication, offering new avenues for personalized and flexible biomedical applications. Full article

Drug delivery systems based on nanoparticles have emerged as promising approaches for overcoming the blood–brain barrier (BBB), a major obstacle to treating disorders of the central nervous system (CNS). There are several reasons why conventional therapies fail, including poor brain penetration, rapid drug clearance, and nonspecific distribution. This review critically evaluates recent advances in nanoparticle-mediated BBB targeting, focusing particularly on in vivo findings. As part of this review, lipid-based, polymeric, metallic, dendrimeric, exosome-inspired, and magnetic nanoparticles are discussed in conjunction with their transport mechanisms. The review compares their therapeutic efficacy, biodistribution, targeting ability, and safety across a variety of neurological conditions. Additionally, emerging technologies are discussed, including biomimetic nanoparticles, stimuli-responsive systems, artificial intelligence, and personalized nanomedicine. Additionally, this review critically discusses the major barriers to clinical translation, including biosafety, manufacturing, and regulatory challenges. As a result, this review provides an updated perspective on current progress and future prospects for developing effective brain-targeted nanomedicine. Full article

Hydrophobins are small, cysteine-rich amphipathic proteins predominantly produced by filamentous fungi, known for their ability to self-assemble at hydrophobic–hydrophilic interfaces. These proteins are essential for fungal development, surface interactions, pathogenicity, and environmental adaptation, and they have attracted growing interest for biotechnological applications. In this work, we provide a narrative review of fungal hydrophobins, based on a systematic literature search and manual curation of eligible studies integrated with protein database records from Ascomycota and Basidiomycota. Information was compiled from peer-reviewed publications selected according to predefined eligibility criteria and complemented with UniProt records, covering taxonomic distribution, functional and biophysical properties, and physiological and pathogenic roles. Significant diversity in molecular features and physicochemical profiles was observed, indicating functional specialization across different ecological niches and lifestyles. Additionally, the compiled data highlight various biotechnological applications, such as surface modification, enzyme immobilization, drug delivery systems, biomaterial development, and environmentally sustainable technologies. By consolidating molecular, functional, and applied information across a wide range of fungal species, this review provides a comprehensive reference framework for hydrophobin research and biotechnological innovation. Full article

Exosomes are small membrane-bound extracellular vesicles of endosomal origin that play pivotal roles in intercellular communication by transferring proteins, lipids, metabolites, and nucleic acids. Increasing evidence indicates that these vesicles participate in diverse physiological and pathological processes, including immune regulation, tissue repair, tumor progression, neurodegeneration, and cardiovascular homeostasis. Their distinctive biological properties have consequently generated considerable interest in their development as diagnostic tools, therapeutic agents, and drug-delivery platforms. Recent progress in exosome biology and biogenesis, together with technological advances in vesicle isolation, characterization, engineering, and large-scale production, has accelerated their preclinical development and early clinical translation. Nevertheless, substantial challenges—including donor-cell heterogeneity, low production yields, insufficiently standardized protocols, and regulatory uncertainty—must be addressed before widespread clinical implementation can be achieved. This narrative review integrates current knowledge of exosome biology, diagnostic and therapeutic applications, and engineering strategies. It further examines major translational barriers and outlines future priorities for advancing exosome-based technologies toward precision medicine. Full article

Oral delivery of bioactive compounds in veterinary medicine offers important opportunities to improve animal health, productivity, and welfare, but its effectiveness is often limited by species-specific gastrointestinal physiology. This review aims to provide a comprehensive overview of microencapsulation strategies for oral veterinary delivery, focusing on species-specific gastrointestinal barriers and the formulation approaches developed to overcome them. Monogastric and ruminant animals present distinct gastrointestinal environments that compromise the stability, bioavailability, and therapeutic performance of orally administered compounds. In monogastrics, gastric acidity, digestive enzymes, gastrointestinal transit, and microbiota-mediated interactions represent major barriers, whereas in ruminants, ruminal fermentation, prolonged retention, and physicochemical conditions may cause premature degradation of bioactive compounds. These barriers significantly hinder the successful use of probiotics, enzymes, essential oils, nutrients, vaccines, and veterinary drugs. However, microencapsulation has emerged as a promising solution, providing a protective barrier that improves compound stability, enhances gastrointestinal survival, and enables controlled or site-specific release. By preserving bioactivity and modulating release kinetics, microencapsulation contributes to improved delivery efficiency and functional performance. A distinctive feature of this review is the integration of species-specific gastrointestinal physiology with microencapsulation technologies to provide a rational framework for designing oral delivery systems in veterinary medicine, rather than focusing solely on individual encapsulation technologies. Current challenges related to material selection, formulation optimisation, and industrial scalability are discussed. Overall, this review highlights that integrating gastrointestinal physiology with advanced microencapsulation technologies is essential for developing effective, targeted, and sustainable oral delivery systems, ultimately supporting improved animal health, productivity, and welfare. Full article

Implantable devices have undergone enormous development in the past several decades and more results are expected as there are still unanswered questions. In manufacturing, a relatively new technology called three-dimensional (3D) printing has become increasingly involved, from which hot-melt extrusion (HME) coupled with fused deposition modeling (FDM) is one of the most researched methods in producing implantable drug delivery systems (IDDS). The HME process is used to produce polymer filaments that are the carriers of the applied drugs, while FDM creates the implant itself from the filaments, based on the computer-aided designs. The availability of several polymers like polycaprolactone, polylactic acid, or thermoplastic polyurethane, etc., allows the incorporation of many active pharmaceutical ingredients while digital designs offer numerous variabilities in designs, formulations, and applications of 3D-printed IDDS. This allows more specific and detailed modifications in the end product which can forecast the possibility of personalized treatments and therapies. In this review, our research group gathered together different HME-FDM-printed IDDS to provide examples about the diverse applicability of 3D printing. These products, just like any other device and medicine in the medical field, must be characterized and evaluated properly. The methods and technology that are needed already exist and can be repeatedly used in the characterization of IDDSs; we also discuss these methods based on the available publications. In conclusion, every condition is given to make research and manufacture personalized 3D-printed IDDSs possible, however more research work and proof of safe usage are crucial to make these devices applicable in everyday medical treatments. Full article

The repair and functional restoration of skeletal muscle tissue following trauma, degenerative disease, or volumetric muscle loss remains a significant unmet clinical challenge in tissue engineering, where the need to recapitulate the anisotropic architecture, mechanical compliance, and high metabolic demands of native muscle imposes stringent requirements on biomaterial design. Traditional cell culturing and scaffold fabrication strategies have proven insufficient to address these demands in isolation, particularly in integrating mechanical integrity, biochemical functionality, and biological activity within a single biomaterial system. Recent advances in material science have accelerated the evolution of skeletal muscle tissue engineering toward a more precise and technologically sophisticated discipline. In this context, surface-engineered magnetic nanoparticle (MNP) hybrids have emerged as a promising multifunctional platform, owing to their intrinsic biocompatibility, tunable physicochemical properties, and rapid, non-invasive responsiveness to external magnetic fields. These unique characteristics have enabled the development of magnetic force-based tissue engineering strategies, facilitating controlled myogenic cell organization, magnetically guided delivery of therapeutic agents and stem cells, enhanced muscle construct formation within responsive scaffolds, and real-time non-invasive monitoring of engineered systems via MRI. This review systematically synthesizes the recent advances in surface-engineered MNP platforms for skeletal muscle tissue engineering, covering organic and inorganic coating strategies, magnetically responsive scaffold integration, guided cell and drug delivery, and construct monitoring, whilst critically appraising the biocompatibility, biodistribution, and regulatory challenges that currently define the translational pathway for MNP-augmented skeletal muscle constructs. Full article

Hydrophobically modified chitosan has attracted considerable interest as an amphiphilic biomaterial for drug delivery, antimicrobial systems, and tissue engineering. Despite extensive research and promising biological performance, only a limited number of these materials have advanced toward clinically relevant technologies. This Perspective argues that the major barriers to translation are no longer related to biological efficacy but to insufficient reproducibility, inconsistent structural characterization, and limited attention to process engineering and scalable manufacturing. Rather than providing another comprehensive review, we discuss hydrophobically modified chitosan from a translational perspective, following its development from chemical modification and self-assembly to formulation engineering and representative biomedical applications. We highlight how molecular design, processing conditions, and material characterization collectively determine the reliability and practical applicability of these systems. Finally, we outline key priorities for future research, including standardized characterization protocols, harmonized experimental methodologies, and the implementation of engineering-oriented development strategies. We propose that future progress will depend less on introducing new chemical modifications and more on integrating polymer chemistry with process engineering to improve reproducibility and facilitate clinical translation. Full article

Plant-Derived Vesicles (PDVs) are natural bioactive nanostructures and potential carriers that hold significant promise for applications in biotherapy and drug delivery. However, their isolation and purification technologies face numerous challenges, including the physical barriers posed by plant cell walls and interference from secondary metabolites. This makes it difficult for existing technologies to achieve both scalable production and high purity. This review evaluates mainstream isolation methods based on six dimensions: operational difficulty, cost, throughput, purity, yield, and impact on vesicle integrity. It also proposes a plant organ-based isolation strategy. Furthermore, this review explores standardized characterisation and quality control strategies for plant exosomes, aiming to provide a standardized and operational technical framework for research in this field. Future research will require standardized production, robust quality control frameworks, and clear elucidation of the action mechanism to promote the clinical application of PDVs. Full article