Frontiers in Bioengineering and Biotechnology最新文献

Diabetes mellitus represents one of the most widespread chronic diseases globally, characterized by alterations in glucose metabolism that require constant monitoring of blood glucose levels. Traditionally, blood testing has been the standard for glucose monitoring; however, interstitial fluid has emerged as a viable alternative, due to its less invasive nature which enhances user comfort. Despite improvements in technology, the accuracy of currently available continuous glucose monitors remains a concern, particularly when the rate of change is higher, such as in hypoglycemic and hyperglycemic ranges. Effective management of hypoglycemia relies on the monitor's ability to provide precise and specific readings when blood glucose levels drop dangerously low. In this context, the demand for heightened accuracy is paramount to timely alert users to impending hypoglycemic events. The inaccuracies of these sensors are attributed to the dynamics of the sample analysis. Specifically the interstitial fluid experiences a delay in concentration due to the diffusion process from capillary blood to interstitial fluid. In this study, we developed a microfluidic device that simulates the diffusion dynamics from capillary glucose to interstitial fluid. We demonstrate the reduction of lag time diffusion from 20 min to 5 min by increasing dermal electro-osmotic flow, which generates convection that transports glucose faster than diffusion, thus resulting in lower lag times. These findings highlight the potential of inciting electro-osmotic flow for improving the responsiveness and accuracy of CGMs, ultimately enhancing diabetes management for users.

Recent advances in nano-biosensors are reshaping clinical diagnostics by enabling multiplexed biomarker detection with high sensitivity and precision. This mini-review examines both the opportunities and challenges in translating nano-biosensor technologies toward clinically relevant point-of-care (PoC) and wearable devices. We emphasize the integration of multiplexing strategies with microfluidic platforms and adaptive artificial intelligence (AI) algorithms, which together enable real-time, high-throughput, and personalized health monitoring. Electrochemical and optical transduction approaches for multi-biomarker diagnostics are discussed, along with the role of microfluidic integration in enhancing sensor performance through precise sample processing, reduced reagent use, and simultaneous biomarker detection. A comparative overview of multiplexing approaches, including spatial, spectral, and temporal encoding is presented, with particular attention to sensor surface regeneration for device reusability. Furthermore, we explore the role of adaptive AI algorithms in individualising diagnostics to diverse patient groups while addressing key ethical and regulatory considerations such as algorithm transparency, patient data protection, and compliance with evolving medical device standards. By drawing together insights across nano-biosensor design, microfluidics, and AI, this mini review provides practical guidance for advancing next-generation diagnostic platforms toward clinical translation.

Objective: Overhanging (OH) attachments were modified clear aligner (CA) attachments with an extended portion toward the root to apply force closer to the center of resistance and enable greater control over root movement, resembling power arms. This study investigated the biomechanical effects of OH attachment and partially gingival extension of CA trimline on canine movement during the closure of extraction space via finite element analysis (FEA).

Methods: CBCT data of an adult with Angle Class I molar relationship and mild anterior crowding was applied for comparing the biomechanical effects of three attachment types (no attachment, vertical, OH) and four trimline designs (partially buccal/lingual gingival coverage). Periodontal ligament (PDL) hydrostatic stress, tooth displacement, rotational center position, and CA stress distribution were assessed via FEA.

Results: OH attachment induced increased tooth displacement and PDL hydrostatic stress (95.5 kPa) compared to regular vertical attachment (53.1 kPa) in achieving root-controlled canine movement. OH attachment combined with a buccolingual gingival extension of CA trimline on 2-6 facilitated the most translational canine movement and lowest ratio of mesio-apical to disto-occlusal displacement (0.466, compared to 0.506 in group with no attachment and trimline extension), while simultaneously avoiding excessive aligner deformation and stress concentration.

Conclusion: Overhanging attachment combined with partial gingival extension of CA trimline significantly enhanced the orthodontic force for premolar extraction cases involving space closure between canines and molars, as a more efficient and feasible design for canine bodily movement.

Introduction: Human mesenchymal stem/stromal cells (hMSCs) hold significant regenerative potential due to their anti-inflammatory and pro-angiogenic secretome. Three-dimensional (3D) hMSC aggregates secrete extracellular vesicles (EVs) with enhanced immunomodulatory properties compared to 2D cultures. However, the clinical translation of hMSC-EVs remains limited by low production yield. This study investigates scalable EV generation from 3D hMSC aggregates in a novel Vertical-Wheel Bioreactor (VWBR), leveraging shear stress-mediated biochemical cues to enhance EV biogenesis and cargo relevant to nerve regeneration.

Methods: Bone marrow-derived hMSCs were cultured as 3D aggregates in VWBRs and exposed to two different culture media-αMEM/FBS (serum-containing) and DMEM/F12/B27 (serum-free)-under three agitation speeds (25, 40, and 64 rpm). Metabolite analysis and qRT-PCR were performed to assess metabolic activity and EV biogenesis, focusing on ESCRT machinery markers. EVs were isolated and evaluated for yield, size, markers, and microRNA cargo. Functional assays were conducted to measure the effects on EVs on Schwann cells under LPS-induced neural inflammation.

Results: VWBR culture resulted in increased expression of EV biogenesis genes and glycolytic pathway markers compared to static culture. The αMEM/FBS (serum-containing) condition was more robust than DMEM/F12/B27 (serum-free) condition. EV yield (EV number per cell) increased by 3-10 fold (in serum-containing medium) in VWBR compared to static culture, with particle sizes ranging from 120-180 nm and appropriate EV marker expression. microRNA-sequencing showed upregulation of miR-29a-3p, miR-451a, miR-224-5p, miR-16-5p, miR-133a-3p, and miR-143-3p, indicating enhanced EV biogenesis, metabolic reprogramming, and immunomodulatory potential. Functionally, VWBR-derived EVs modulated inflammatory gene expression in Schwann cells exposed to LPS.

Discussion: VWBR-driven hydrodynamics promotes EV biogenesis from 3D hMSC aggregates, improving metabolic activity, EV cargo relevance, and functional efficacy. The resulting EVs exhibit therapeutic cargo capable of modulating neural inflammation. These findings advance understanding of dynamic aggregation on metabolic cues and EV production, demonstrating a scalable strategy for generating therapeutically potent hMSC-EVs for neuropathic and regenerative applications.

Carotenoids and apocarotenoids constitute a structurally and functionally sundry class of isoprenoids whose significance extends from photosynthetic light capture and photoprotection to phytohormone signaling, flavor and aroma formation, and emerging biomedical applications. While recent appraisals have emphasized quantitative advances in microbial production, this mini-review adopts a pathway module-centric perspective. We examine each biosynthetic stage from precursor supply, condensation to geranylgeranyl diphosphate (GGPP), phytoene synthesis, desaturation/isomerization, cyclization, hydroxylation, ketolation, epoxidation, and oxidative cleavage, highlighting novel enzymatic variants, mutagenesis studies, fusion strategies, and compartmentalization approaches that impart metabolic control. Special emphasis is placed on recently discovered and engineered enzymes, as well as synthetic biology tools. This review integrates diverse enzyme sources, host ranges across plants, fungi, algae, yeasts, and bacteria, as well as pathway modularity, to provide an updated review of recent literature. We conclude by outlining future directions that highlight gaps and potential areas for future work. This focused synthesis aims to equip researchers with a hierarchical understanding of the pathways and strategies to advance carotenoid and apocarotenoid biosynthesis.

Background: Accurate and reproducible quantification of LA anatomy from CTA is essential for ablation, LAAC, and structural interventions, yet manual measurements are time-consuming and prone to inter-observer variability.

Objectives: To validate a deep learning-based CTA pipeline for automated quantification of eight clinically relevant LA metrics, and to assess its agreement, repeatability, and efficiency compared with expert measurements.

Methods: In this retrospective study, 407 patients were included and divided into training (n = 270), validation (n = 87), and clinical evaluation (n = 50) cohorts. A MedNeXt-based model performed multi-structure segmentation, and a geometry-driven framework computed eight metrics: LA volume, LAA volume, AP/ML/SI diameters, left/right PV ostial size, left/right PV inter-ostial angles, and LAA ostial size. Automated outputs were compared with expert annotations using intraclass correlation coefficients (ICCs) and Bland-Altman analysis (primary endpoints: LA volume and diameters). Workflow efficiency and usability (Likert scale, 1-5) were also assessed by electrophysiology/structural experts.

Results: Automated measurements demonstrated excellent agreement with experts for primary endpoints (LA volume ICC = 0.999; AP/ML/SI diameter ICCs = 0.972-0.985), with minimal bias and narrow limits of agreement. Agreement for other metrics was good to excellent (typical ICCs ≥0.84). Analysis time was reduced from 15.3 ± 1.4 min to 0.5 ± 0.1 min per case (≈92% reduction; p < 0.001). Usability ratings were ≥4/5 in most cases, with 63%-76% classified as Grade A (fully usable without manual edits). Performance remained consistent across voxel-size strata.

Conclusion: The proposed pipeline enables rapid, reproducible, and expert-level quantification of eight LA metrics on CTA, demonstrating technical feasibility for clinical integration pending prospective validation of procedural impact.

United States (U.S.) poliovirus research and vaccination programs have eliminated polio in the U.S. and brought the world to the brink of polio eradication. As part of a global action plan, the U.S. committed to safeguard the polio eradication efforts through identification of domestic facilities holding poliovirus materials and implementing stringent laboratory biocontainment measures overseen by U.S. CDC. In January 2025, the White House announced the withdrawal of the U.S. from the WHO. Consistent with the administration's policy and guidance, the U.S. CDC is developing a new framework for poliovirus containment independent of WHO to protect the health security of the U.S. from the continued threat of poliovirus and ensure the long-term success of polio eradication.

Introduction: Bacterial wound infections that lead to sepsis pose a major clinical challenge. This study aims to develop and optimize a novel cross-linked poly(acrylic acid)/carboxymethylcellulose sodium (PAA/CMC-Na) hydrogel encapsulating liquiritigenin (LQ) to improve wound healing and infection control.

Methods: The hydrogel matrix was optimized using response surface methodology (RSM). Mechanical properties, self-healing efficiency, and pH-responsive swelling behavior were characterized. In vitro drug release profiles were evaluated over 24 h, and molecular docking simulations were performed to assess the binding affinity of LQ to key sepsis targets. Biological safety was tested using CCK-8 and Trypan blue assays, while anti-inflammatory and antibacterial activities were evaluated using LPS-stimulated RAW264.7 macrophages and pathogen inhibition assays (E. coli and S. aureus).

Results: The optimized hydrogel achieved a high model fit (R2 = 0.976$) and exhibited superior mechanical performance, including 776% tensile strain and 100% self-healing efficiency. Swelling was pH-responsive (∼600% at pH 5.5 vs. ∼450% at pH 7.4). LQ showed sustained release (>90% over 24 hours) and strong binding affinity to sepsis-related targets. Biological assays confirmed high biocompatibility (>98% fibroblast viability). Furthermore, the hydrogel significantly reduced inflammatory cytokines (TNF-α, IL-6, IL-1β) in a dose-dependent manner and effectively inhibited the growth of E. coli and S. aureus.

Discussion: These findings demonstrate that the LQ-loaded hydrogel possesses excellent mechanical, biocompatible, and anti-inflammatory properties. Its dual-action as a pro-healing and antibacterial agent suggests it is a promising candidate for topical wound management and the prevention of infection-induced sepsis.

Heavy metals are essential for technological and economic growth but can cause serious environmental and health problems due to their toxicity and persistence. Traditional methods for metal recovery often have high costs and can create secondary pollution. Bioleaching offers a sustainable, low-energy, and eco-friendly alternative, effectively recovering metals from low-grade ores and various waste materials. Recovering metals from secondary sources such as industrial and electronic waste reduces the need for new mining, thus conserving natural resources and supporting circular economic goals. Recently, biomining has expanded beyond Earth, showing promising results in space environments. This review discusses the current understanding of bioleaching processes, their potential for sustainable metal recovery on Earth and in space, their challenges, and future perspectives. Overcoming technical challenges, such as raw material composition, slow reaction kinetics, optimization of process parameters, and addressing safety concerns is crucial. A further increase in research focus aiming at scaling up bioleaching technology is essential, alongside addressing ethical and economic concerns related to space mining.