Search Results (1,995)

Continuous, label-free particle separation is essential for a broad range of biochemical and biomedical applications. Here, we present a microfluidic device that integrates inertial focusing and deterministic lateral displacement (DLD) within a compact channel architecture to achieve size-based particle sorting under laminar flow conditions. The design combines upstream curved channels for initial lateral positioning with downstream micropillar-embedded curved channels to enhance separation resolution. Theoretical analysis and numerical simulations were performed to optimize channel geometry and micropillar arrangement, predicting size-dependent lateral displacement driven by centrifugal forces and pillar-induced constraints. Experimental validation using glass beads of two distinct sizes (8 μm and 15 μm) demonstrated a separation efficiency exceeding 93% across a range of flow rates and particle concentrations. The device offers a simple, cost-effective, and scalable solution for passive particle sorting without external fields or labeling. The flexibility of the design configuration can be adapted for diverse applications, including extracellular vesicles, barcoded hydrogel particles, and engineered drug-delivery carriers. Full article

Controlled drug delivery systems (CDDSs) are increasingly attracting interest from the scientific community in order to achieve highly precise, customized, and efficient therapeutic treatment of various diseases. The challenge is to develop highly innovative devices and appropriate administration methods in order to reduce side effects and further improve patient compliance. In this context, transdermal drug delivery systems (TDDSs) represent smart tools that permit supplying therapeutically effective amounts of drugs at a fixed time using the skin as the administration route. They are non-invasive and allow for avoiding gastric side effects and first-pass metabolism occurring in the liver. TDDSs have been produced using numerous therapeutic agents and, more recently, also biological molecules. However, it must be highlighted that they are complex systems, and their formulation requires a multidisciplinary approach and expertise in polymer chemistry and materials science. A contribution in this direction is given from the integration of membrane technology with biological and pharmaceutical sciences. The present review deals with a general overview of controlled drug delivery systems. Particular attention is devoted to TDDSs and to the materials used for producing polymeric membrane-based TDDSs with a membrane engineering perspective. It also describes the passive and the most advanced active strategies for transdermal delivery. Finally, different transdermal membrane-based release systems, like patches, mixed-matrix membranes, and imprinted membranes are discussed. Full article

Background/Objectives: Peritoneal metastases (PMs) remain difficult to treat because the peritoneum–plasma barrier limits drug penetration from the systemic circulation. Intraperitoneal chemotherapy (IPC), particularly repeated intraperitoneal (IP) administration via implantable ports, can achieve high local drug exposure with prolonged retention. This review summarizes the pharmacological rationale, clinical evidence, and future directions of catheter-based IPC, with emphasis on combined IP and systemic chemotherapy for ovarian, gastric, and pancreatic cancers. Methods: We narratively reviewed prospective clinical trials and key retrospective studies evaluating IPC and compared repeated catheter-based IPC with hyperthermic intraperitoneal chemotherapy (HIPEC) and pressurized intraperitoneal aerosol chemotherapy (PIPAC). Efficacy, safety, practice considerations, and opportunities for ascites-based monitoring were examined. Results: In ovarian cancer, several randomized trials demonstrated improved progression-free survival (PFS), and in selected trials, improved overall survival (OS) was demonstrated using IP plus intravenous (IV) therapy, although in the latter trials, toxicity and catheter-related complications limited treatment completion. A phase III Intraperitoneal Therapy for Ovarian Cancer with Carboplatin (iPocc) trial further showed significantly prolonged PFS with IP carboplatin and weekly paclitaxel, with non-catheter-related toxicity comparable to that of IV therapy. In gastric and pancreatic cancer, phase II studies reported symptomatic control, cytologic conversion, and higher rates of conversion surgery in selected patients, although confirmatory phase III data are limited. Device complications, including infection, obstruction, and leakage, occurred, but were manageable. Conclusions: Repeated catheter-based IPC is a feasible approach that enhances intraperitoneal drug delivery and complements IV chemotherapy. Future priorities include randomized trials, pharmacokinetic optimization, and biomarker-guided patient selection, supported by serial ascites assessment to refine indications and improve outcomes. Full article

Healthcare 5.0 and the Internet of Medical Things (IoMT) is emerging as a scalable model for the delivery of customised healthcare and chronic disease management, through Remote Patient Monitoring (RPM) in patient smart home environments. Large-scale RPM initiatives are being rolled out by healthcare providers (HCPs); however, the constrained nature of IoMT devices and proximity to poorly administered smart home technologies create a cyber risk for highly personalised patient data. The recent Network and Information Systems (NIS 2) directive requires HCPs to improve their cyber risk management approaches, mandating heavy penalties for non-compliance. Current research into cyber risk management in smart home-based RPM does not address scalability. This research examines scalability through the lens of the Non-adoption, Abandonment, Scale-up, Spread and Sustainability (NASSS) framework and develops a novel Scalability Index (SI), informed by a PRISMA guided systematic literature review. Our search strategy identified 57 studies across major databases including ACM, IEEE, MDPI, Elsevier, and Springer, authored between January 2016 and March 2025 (final search 21 March 2025), which focussed on cyber security risk management in the RPM context. Studies focussing solely on healthcare institutional settings were excluded. To mitigate bias, a sample of the papers (30/57) were assessed by two other raters; the resulting Cohen’s Kappa inter-rater agreement statistic (0.8) indicating strong agreement on study selection. The results, presented in graphical and tabular format, provide evidence that most cyber risk approaches do not consider scalability from the HCP perspective. Applying the SI to the 57 studies in our review resulted in a low to medium scalability potential of most cyber risk management proposals, indicating that they would not support the requirements of NIS 2 in the RPM context. A limitation of our work is that it was not tested in a live large-scale setting. However, future research could validate the proposed SI, providing guidance for researchers and practitioners in enhancing cyber risk management of large-scale RPM initiatives. Full article

Following the discovery of therapeutic molecules and the identification of specific biological targets, preparation of regulatory dossiers entails extensive product development and characterization to support their safety, efficacy, and stability. We have examined the drug development and relevant regulatory considerations related to inhaled biological proteins in the accompanying article. This review focuses on the characterization of locally acting inhaled biological proteins. Drug product characterization is a regulatory requirement, and it ensures drug product safety, efficacy, stability, and usability by the target populations. Together, these two articles provide a comprehensive discussion based on our review and analysis of the available open literature. We have attempted to fill gaps and simulate discussion of challenges following sound scientific pathways. This approach has the prospect of addressing regulatory expectations leading to rapid solutions to unmet medical needs. The robustness of characterization strategies and the development of analytical methods used in the in vitro testing for the evaluation of drug product attributes is assured through application of the Design-of-Experiment (DOE) and Quality-by-Design (QBD) approaches. Drug product characterization entails a variety of in vitro studies evaluating drug products for purity and contamination, and determination of drug delivery by the intended route of administration. Measurement of the proportion of the labeled amount per dose and the form suitable for delivery to the intended target sites is central to this assessment. For respiratory Drug–Device combination products, the testing may vary with the product designs. However, determination of the single-dose content, delivered-dose uniformity, aerodynamic particle size distribution, and device robustness when used by the target populations is common to all combination products. Characterization of aerosol plumes is limited to inhalation aerosols that produce specific aerosol clouds upon actuation. The flow rate dependency of devices is also examined. Product characterization also includes safety-related product attributes such as degradation products and leachables. For inhaled biological proteins, safety-related in vitro testing includes additional testing to assure maintenance of the three-dimensional structural integrity and the sustained biological activity of the drug substance in the formulation, during aerosolization and upon deposition. This article discusses various tests employed for regulatory-compliant product characterization. In addition, the stability testing and handling of possible changes during product development and post-approval are discussed. Full article

In recent years, flying ad hoc networks (FANETs) have attracted attention as aerial communication platforms for large-scale disasters. In wide, city-scale disaster zones, survivors’ devices often form multiple isolated clusters, while battery-powered unmanned aerial vehicles (UAVs) must periodically return to a ground station (GS). Under such conditions, conventional delay/disruption-tolerant networking (DTN) routing (e.g., PRoPHET) often traps bundles in clusters or UAVs, degrading the bundle delivery ratio (BDR) to the GS. This study proposes a DTN-based FANET architecture that integrates (i) a mobility model assigning UAVs to information–exploration UAVs that randomly patrol the disaster area and GS–relay UAVs that follow spoke-like routes to periodically visit the GS, and (ii) an extended PRoPHET-based routing protocol that exploits exogenous information on GS visits to bias delivery predictabilities toward GS–relay UAVs and UAVs returning for recharging. Simulations with The ONE in a 10 km × 10 km scenario with multiple clusters show that the proposed method suppresses BDR degradation by up to 41% relative to PRoPHET, raising the BDR from 0.27 to 0.39 in the five-cluster case and increasing the proportion of bundles delivered with lower delay. These results indicate that the proposed method is well-suited for relaying critical disaster-related information. Full article

Accurate trajectory tracking is a key requirement in unmanned ground vehicles (UGVs) operating in autonomous driving, mobile robotics, and industrial automation. In wireless Time-Sensitive Networking (WTSN) scenarios, trajectory accuracy strongly depends on deterministic packet delivery, precise traffic scheduling, and time synchronization among distributed devices. This paper quantifies the impact of IEEE 802.1Qbv time-aware traffic scheduling on trajectory tracking accuracy in UGVs operating over Wi-Fi-enabled TSN networks. The analysis focuses on how misconfigured real-time (RT) and best-effort (BE) transmission windows, as well as clock misalignment between devices, affect packet reception and control performance. A mathematical framework is introduced to predict the number of correctly received RT packets based on cycle time, packet periodicity, scheduling window lengths, and synchronization offsets, enabling the a priori dimensioning of RT and BE windows. The proposed model is validated through extensive simulations conducted in an ROS–Gazebo environment, utilising Linux-based traffic shaping and scheduling tools. Results show that improper traffic scheduling and synchronization offsets can significantly degrade trajectory tracking accuracy, while correctly dimensioned scheduling windows ensure reliable packet delivery and stable control, even under imperfect synchronization. The proposed approach provides practical design guidelines for configuring wireless TSN networks supporting real-time trajectory tracking in mobile robotic systems. Full article

Mechano-Organ-on-Chip (Mechano-OoC) platforms are emerging as powerful microphysiological systems that place mechanical cues at the center of tumor modeling, providing a scalable and human-relevant approach to recapitulate the biophysical complexity of the tumor microenvironment. Mechanical factors such as matrix stiffness, viscoelasticity, solid stress, interstitial flow, confinement, and shear critically regulate cancer progression, metastasis, immune interactions, and treatment response, yet remain poorly captured by conventional in vitro models and are often studied separately in tumor-on-chip and mechanobiology research. In this review, we summarize recent advances in mechano-OoC technologies for cancer research, highlighting strategies that integrate engineered mechanical cues with microfluidics, tunable extracellular matrices, vascular and stromal interfaces, and dynamic loading to model tumor invasion, vascular transport, immune trafficking, and drug delivery. We also discuss emerging approaches for real-time, multimodal readouts, including sensor-integrated platforms and artificial intelligence-assisted data analysis, and outline key challenges that limit translation, such as device complexity, limited throughput, insufficient standardization, and inadequate validation against in vivo and clinical data. By organizing progress across platform engineering, sensing and readout, data standardization, and AI-driven analytics, this review provides a unified framework for advancing mechanobiology-aware tumor models and guiding the development of predictive preclinical platforms for precision cancer therapy. Full article

This paper proposes an efficient and automated smart healthcare communication framework that integrates a two-level filtering scheme with a multi-objective Genetic Algorithm (GA) to enhance the reliability, timeliness, and energy efficiency of Internet of Medical Things (IoMT) systems. In the first stage, physiological signals collected from heterogeneous sensors (e.g., blood pressure, glucose level, ECG, patient movement, and ambient temperature) were pre-processed using an adaptive least-mean-square (LMS) filter to suppress noise and motion artifacts, thereby improving signal quality prior to analysis. In the second stage, a GA-based optimization engine selects optimal routing paths and transmission parameters by jointly considering end-to-end delay, Signal-to-Noise Ratio (SNR), energy consumption, and packet loss ratio (PLR). The two-level filtering strategy, i.e., LMS, ensures that only denoised and high-priority records are forwarded for more processing, enabling timely delivery for supporting the downstream clinical network by optimizing the communication. The proposed mechanism is evaluated via extensive simulations involving 30–100 devices and multiple generations and is benchmarked against two existing smart healthcare schemes. The results demonstrate that the integrated GA and filtering approach significantly reduces end-to-end delay by 10%, as well as communication latency and energy consumption, while improving the packet delivery ratio by approximately 15%, as well as throughput, SNR, and overall Quality of Service (QoS) by up to 98%. These findings indicate that the proposed framework provides a scalable and intelligent communication backbone for early disease detection, continuous monitoring, and timely intervention in smart healthcare environments. Full article

Cystic fibrosis (CF) is caused by loss-of-function variants in the cystic fibrosis transmembrane conductance regulator (CFTR) chloride and bicarbonate channel and affects multiple organs, with pancreatic involvement showing very high penetrance. In pancreatic ducts, CFTR drives secretion of alkaline, bicarbonate-rich fluid that maintains intraductal patency, neutralises gastric acid and permits safe delivery of digestive enzymes. Selective impairment of CFTR-dependent bicarbonate transport, even in the presence of residual chloride conductance, is strongly associated with exocrine pancreatic insufficiency, recurrent pancreatitis and cystic-fibrosis-related diabetes. These clinical manifestations are captured by pharmacodynamic anchors such as faecal elastase-1, steatorrhoea, pancreatitis burden and glycaemic control, providing clinically meaningful benchmarks for CFTR-targeted therapies. In this review, we summarise the principal mechanisms underlying pancreatic pathophysiology and the current approaches to clinical management. We then examine in vitro pancreatic duct models that are used to evaluate small molecules and emerging therapeutics targeting CFTR. These experimental systems include native tissue, primary cultures, organoids, co-cultures and microfluidic devices, each of which has its own advantages and limitations. Intact micro-perfused ducts provide the physiological benchmark for studying luminal pH control and bicarbonate (HCO₃⁻) secretion. Primary pancreatic duct epithelial cells (PDECs) and pancreatic ductal organoids (PDO) preserve ductal identity, patient-specific genotype and key regulatory networks. Immortalised ductal cell lines grown on permeable supports enable scalable screening and structure activity analyses. Co-culture models and organ-on-chip devices incorporate inflammatory, stromal and endocrine components together with flow and shear and provide system-level readouts, including duct-islet communication. Across this complementary toolkit, we prioritise bicarbonate-relevant endpoints, including luminal and intracellular pH and direct measures of HCO₃⁻ flux, to improve alignment between in vitro pharmacology and clinical pancreatic outcomes. The systematic use of complementary models should facilitate the discovery of next-generation CFTR modulators and adjunctive strategies with the greatest potential to protect both exocrine and endocrine pancreatic function in people with CF. Full article

Background/Objectives: Older adults often face nutrition challenges due to mobility issues, chronic conditions, and limited access to adequate nutrition. Digital and technology-based interventions, including those with nutrition education, nutrition counseling and Medically Tailored Meals [MTMs], can help address these barriers. However, the extent and characteristics of such programs in the United States remain unclear. This scoping review aimed to map the existing evidence on digital and technology-based (“digi-tech”) nutrition interventions for older adults in the United States, with particular attention to the presence, characteristics, and gaps related to MTMs. Methods: This scoping review followed the PRISMA-ScR framework to map existing evidence on technology-enabled nutrition care interventions for older adults aged ≥ 60 years in the United States. Systematic searches were conducted across multiple databases, yielding 18,177 records. Following title and abstract screening, full-text review, and eligibility assessment, 16 intervention studies were included. Study designs comprised randomized controlled trials, quasi-experimental and non-randomized studies, mixed-methods feasibility studies, pilot studies, and one retrospective longitudinal cohort study. Data were extracted on study design, population characteristics, intervention components, technology modalities, outcomes, feasibility, acceptability, and reported barriers. Results: Interventions varied in duration [8 weeks to ≥12 months] and content. Foci ranged from remote nutrition education and mobile app-based tracking to multicomponent interventions integrating exercise, nutrition counseling, health literacy, and meal delivery. Telehealth was the most commonly used technology modality, followed by mobile health applications, wearable devices, and online educational platforms. Most interventions reported high feasibility and acceptability, with improvements in diet quality, adherence to healthy eating patterns, clinical measures such as HbA1c and blood pressure, and functional performance. Common implementation barriers included declining technology use over time, digi-tech literacy, and access to devices or the internet. Notably, no studies evaluated a digi-tech-based MTMs intervention exclusively for older adults in the U.S. Conclusions: Digital and technology-based nutrition interventions show promise for improving dietary and health outcomes in older adults, but there is insufficient empirical evidence. Future research might develop and evaluate hybrid digi-tech intervention models that leverage the potential of digi-tech tools while addressing barriers to technology adoption among older adults. Full article

Background: Solid microneedles (MNs) are effective transdermal delivery devices but are commonly fabricated from metallic or non-biodegradable materials, raising concerns related to sustainability, waste management, and processing constraints. This study aimed to evaluate the suitability of the biodegradable biopolyester poly(3-hydroxybutyrate-co-3-hydroxyvalerate-co-3-hydroxyhexanoate) (PHBHVHHx) as a structuring material for solvent-free fabrication of solid MN arrays and to assess their mechanical performance, insertion capability, and drug delivery potential. Methods: PHBHVHHx MN arrays were fabricated by solvent-free micromolding at 200 °C. The resulting MNs were morphologically characterized by scanning electron microscopy. Mechanical properties were assessed by axial compression testing, and insertion performance was evaluated using a multilayer Parafilm skin simulant model. Diclofenac sodium was used as a model drug and applied via surface coating using a FucoPol-based formulation. In vitro drug release was assessed in phosphate-buffered saline under sink conditions and quantified by UV–Vis spectroscopy. Results: PHBHVHHx MN arrays consisted of sharp, well-defined conical needles (681 ± 45 µm length; 330 µm base diameter) with micro-textured surfaces. The MNs withstood compressive forces up to 0.25 ± 0.03 N/needle and achieved insertion depths of approximately 396 µm in the Parafilm model. Drug-coated MNs retained adequate mechanical integrity and exhibited a rapid release profile, with approximately 73% of diclofenac sodium released within 10 min. Conclusions: The results demonstrate that PHBHVHHx is a suitable biodegradable thermoplastic for the fabrication of solid MN arrays via a solvent-free process. PHBHVHHx MNs combine adequate mechanical performance, reliable insertion capability, and compatibility with coated drug delivery, supporting their potential as sustainable alternatives to conventional solid MN systems. Full article

Next-generation therapeutic devices will rely on an intelligent integrated system that consolidates multiple functions into a single platform. These individual chemical components exhibit diverse physicochemical properties, demonstrating multifunctional characteristics. In this review, we focus on how the distinctive properties of upconversion nanoparticles (UCNPs), achieved via refined preparation methods, unlock novel functionalities in biomedical applications. Specifically, features such as near-infrared excitation, deep-tissue penetration, low autofluorescence, and tunable multicolor emission endow UCNPs with substantial potential in fields including deep-tissue imaging, targeted drug delivery, and photodynamic therapy. This article systematically reviews recent advances in the design and functionalization of UCNPs, elucidating their role in facilitating the development of integrated diagnostic and therapeutic platforms and fostering the establishment of intelligent responsive treatment systems. Finally, we address current technical challenges—including uniformity in large-scale production, long-term biosafety, and in vivo metabolic mechanisms—and provide insights into future interdisciplinary integration, clinical translation pathways, and their potential role in personalized medicine. Full article

Accurate immobilization is critical in head and neck (H&N) radiotherapy to ensure precise dose delivery while minimizing irradiation of surrounding healthy tissues. However, conventional thermoplastic masks cannot secure 100% replicas of the patient’s surface and are often limited by mechanical weakness, patient discomfort, and workflow inefficiencies. Recently, the best replicas of the patient’s face have been obtained by exploring personal CT or MRI scans of patients that are used for manufacturing of immobilization masks. This study aimed to design and evaluate customizable immobilization masks using acrylonitrile butadiene styrene (ABS)-based composites reinforced with bismuth oxide (Bi₂O₃) and to compare their mechanical performance against commercial thermoplastic masks. ABS and ABS/Bi₂O₃ composite filaments (5, 10, and 20 wt%) were fabricated and characterized by tensile testing. A patient-specific virtual mask was modeled and subjected to finite element analysis (FEA) under clinically relevant loading scenarios, including neck flexion and lateral bending. Results were benchmarked against two commercial thermoplastic masks. ABS and ABS-based composites exhibited significantly higher stiffness (1.7–2.5 GPa) and yield strength (20–25 MPa) compared to commercial thermoplastics (0.25–0.3 GPa, ~7 MPa; p < 0.001). FEA simulations revealed markedly reduced displacement in ABS masks (1–5 mm at 2 mm thickness; <1 mm at 4 mm thickness) relative to commercial masks, which exceeded 20 mm under lateral load. Hybrid configurations with reinforced edges further optimized rigidity while limiting material usage. Customized ABS-based immobilization masks outperform conventional thermoplastics in mechanical stability and displacement control, with the potential to reduce planning margins and improve patient comfort. In addition, ABS-based masks can be recycled, and Bi₂O₃-filled composites can be reused for printing new immobilization masks, thus contributing to a reduced amount of plastic waste. These findings support their promise as next-generation immobilization devices for precision radiotherapy, warranting further clinical validation, workflow integration and sustainable implementation within a circular economy. Full article

Background: Although surfactant replacement therapy has been a cornerstone of respiratory distress syndrome (RDS) management for decades, traditional delivery via endotracheal intubation and mechanical ventilation is associated with procedure-related complications and increased risk of bronchopulmonary dysplasia (BPD). These concerns have driven the development of less invasive surfactant administration strategies. Objective: This review aims to summarize and evaluate the current literature on less invasive surfactant delivery techniques used in preterm infants with RDS, with a focus on their feasibility, efficacy, and short- and long-term neonatal outcomes. Methods: We reviewed the available literature evaluating less invasive surfactant administration methods, including InSurE, Less Invasive Surfactant Therapy/Minimally Invasive Surfactant Therapy (LISA/MIST), surfactant administration via laryngeal mask airway (SALSA/LMA), pharyngeal administration, and nebulized surfactant. We compared major outcomes, namely the need for mechanical ventilation, incidence of BPD, procedural complications and long-term neurodevelopmental outcomes. Results: Non-invasive surfactant administration techniques have been associated with reduced exposure to mechanical ventilation and lower rates of BPD compared with conventional approaches. Studies on LISA/MIST demonstrate the most consistent evidence in reducing the need for mechanical ventilation and BPD, while other techniques such as LMA-assisted delivery and nebulization show promise but remain limited by device constraints, gestational age applicability, and heterogeneous study designs. Long-term neurodevelopmental outcome data remain sparse across all techniques. Conclusions: Non-invasive surfactant administration represents an important advancement in the management of RDS. While several techniques offer potential advantages over traditional intubation-based delivery, further high-quality studies are required to optimize patient selection, standardize techniques, develop safe and effective delivery devices, and evaluate long-term neurodevelopmental outcomes. Full article