Search Results (1,150)

Stroke remains a leading cause of disability worldwide, underscoring the urgent need for novel and innovative therapeutic strategies to enhance neuroprotection, support regeneration, and improve functional recovery. Previous research has shown that phytochemicals such as curcumin, tannic acid, gallic acid, ginsenosides, resveratrol, and isorhamnetin display extensive neuroprotective properties, including antioxidant, anti-inflammatory, and anti-apoptotic effects. These natural compounds could also promote neurogenesis, angiogenesis, and the preservation of the blood–brain barrier. Despite their promising bioactivities, clinical application is often limited by poor solubility, bioavailability, and suboptimal pharmacokinetics. Hydrogels offer a promising solution by encapsulating and controlling the gradual release of these phytochemicals directly at the site of injury. Recent advancements in hydrogel formulations, constructed from biopolymers and functionalized using nanotechnological approaches, could significantly improve the solubility, stability, and targeted delivery of phytochemicals. Controlled release profiles from pH-sensitive and environment-responsive hydrogels could ensure that the compounds’ therapeutic effects are optimally timed with individual and critical stages of post-stroke repair. Moreover, hydrogel scaffolds with tailored material properties and biocompatibility can create a favorable microenvironment, reducing secondary inflammation, enhancing tissue regeneration, and potentially improving functional and cognitive outcomes following stroke. This review explores the potential of integrating phytochemicals within hydrogel-based delivery systems specifically designed for post-stroke recovery. The design and synthesis of biocompatible, biodegradable hydrogels functionalized especially with phytochemicals and their applications are also discussed. Lastly, we emphasize the need for additional robust and translatable preclinical studies. Full article

This article reports on the first qualitative phase of an exploratory sequential mixed method (ESMM) research design focusing on EFL pronunciation instruction in Spanish primary schools. Firstly, it presents an analysis of the National Curriculum in light of recent policy changes and adaptations across seventeen Autonomous Communities (AACC) to assess coherence and the scaffolding of contents. Secondly, based on results from Focus Groups with eight instructors from five different schools and two different AACC, teachers’ perceptions on EFL pronunciation teaching in the current curriculum change are examined according to two main strands, i.e., Curriculum Design and Development and Teacher Professional Development. The results reveal asymmetries in Curriculum Contents regarding specificity and teaching methodologies, as well as some conceptual inconsistencies and dispositions that seem to be leading to overregulation, particularly in relation to increased measures of public accountability. These appear to be heightening tensions that are causing a mismatch between the intended Curriculum and the instructor-experienced curriculum. Another key observation is that, in this scenario, the positive beliefs and attitudes of primary school teachers towards EFL pronunciation are insufficient for optimal teaching. Intervention measures and innovations are suggested to improve the situation, which may be extrapolated to other similar EFL contexts. Full article

Cardiovascular disease (CVD) remains the leading cause of death globally, with myocardial infarction (MI) being a major contributor. The current therapeutic approaches are limited in effectively regenerating damaged cardiac tissue. Up-to-date strategies for heart regeneration/reconstitution aim at cardiac remodeling through repairing the damaged tissue with an external cell source or by stimulating the existing cells to proliferate and repopulate the compromised area. Cell reprogramming is addressed to this challenge as a promising solution, converting fibroblasts and other cell types into functional cardiomyocytes, either by reverting cells to a pluripotent state or by directly switching cell lineage. Several strategies such as gene editing and the application of miRNA and small molecules have been explored for their potential to enhance cardiac regeneration. Those strategies take advantage of cell plasticity by introducing reprogramming factors that regress cell maturity in vitro, allowing for their later differentiation and thus endorsing cell transplantation, or promote in situ cell proliferation, leveraged by scaffolds embedded with pro-regenerative factors promoting efficient heart restoration. Despite notable advancements, important challenges persist, including low reprogramming efficiency, cell maturation limitations, and safety concerns in clinical applications. Nonetheless, integrating these innovative approaches offers a promising alternative for restoring cardiac function and reducing the dependency on full heart transplants. Full article

Poly (lactic acid) (PLA), a biodegradable polymer, is widely used in medical applications, particularly for 3D-printed tissue engineering scaffolds. The fused filament fabrication (FFF) 3D printer is an available processing tool for PLA. The nozzle scan pattern and interior fill percentage (IFP) considerably influence the mechanical properties of formed structures and may have dominant effects on the rates at which the mechanical properties of PLA deteriorate. When the IFP is set to a low value, such as 80%, internal gaps form within the structure, leading to different deterioration patterns compared to structures formed under the IFP 100% condition. In this study, we fabricated test pieces with an FFF 3D printer using three different nozzle scan patterns. After immersing the test pieces in phosphate buffer saline (PBS) for up to 120 days, the water content was measured and the test pieces underwent tensile testing to determine the tensile strength, elastic modulus, and breaking energy. Both the deterioration rate and water uptake rate varied among the different nozzle scan patterns used for the fabrication. For the test pieces formed with internal gaps, the water uptake and deterioration proceeded in two stages. The deterioration rate of the structures with internal gaps was faster than that of the fully filled structures. The data obtained in this study will be useful for the design of PLA structures applied in tissue engineering. Full article

Spinal cord injury (SCI) is a life-altering condition that leads to severe neurological deficits and significantly impacts patients’ quality of life. Despite advancements in medical care, current treatment options remain largely palliative, with limited ability to promote meaningful functional recovery. Induced pluripotent stem cells (iPSCs) have emerged as a promising avenue for regenerative medicine, offering patient-specific, cell-based therapeutic potential for SCI repair. This review provides a comprehensive overview of recent advancements in iPSC-based approaches for SCI, detailing the strategies used to generate neural cell types, including neural progenitor cells, oligodendrocytes, astrocytes, and microglia, and their roles in promoting neuroprotection and regeneration. Additionally, we examine key preclinical and clinical studies, highlighting functional recovery assessments and discussing both standardized and debated evaluation metrics. Furthermore, we address critical challenges related to safety, tumorigenicity, immune response, survival, integration, and overcoming the inhibitory microenvironment of the injured spinal cord. We also explore emerging approaches in biomaterial scaffolds, gene editing, and rehabilitation strategies that may enhance the clinical applicability of iPSC-based therapies. By addressing these challenges and refining translational strategies, iPSC-based interventions hold significant potential to revolutionize SCI treatment and improve outcomes for affected individuals. Full article

Ischemic heart disease (IHD) is the leading cause of mortality worldwide, underscoring the urgent need for innovative therapeutic strategies. The cardiac extracellular matrix (ECM) undergoes extreme transformations during IHD, adversely influencing the heart’s structure, mechanics, and cellular signaling. Researchers investigating the regenerative capacity of the diseased heart have turned their attention to exploring the modulation of ECM to improve therapeutic outcomes. In this review, we thoroughly examine the current state of knowledge regarding the cardiac ECM and its therapeutic potential in the ischemic myocardium. We begin by providing an overview of the fundamentals of cardiac ECM, focusing on the structural, functional, and regulatory mechanisms that drive its modulation. Subsequently, we examine the ECM’s interactions within both chronically ischemic and acutely infarcted myocardium, emphasizing key ECM components and their roles in modulating angiogenesis. Finally, we discuss recent ECM-based approaches in biomedical engineering, focusing on different types of scaffolds as delivery tools and their compositions, and conclude with future directions for therapeutic research. By harnessing the potential of these emerging ECM-based therapies, we aim to contribute to the development of novel therapeutic modalities for IHD. Full article

Greenhouse cultivation in Almería, Spain, has experienced continuous growth over the last five decades, and this area has established itself as one of Europe’s leading vegetable-producing regions. With 8201 hectares under cultivation, tomatoes are the most important crop, accounting for 63% of the total value of greenhouse tomato production in Spain. The aim of this study is to design and develop a tool that facilitates tomato trellising under greenhouse conditions and allows it to be carried out at the ground level. An operating principle is developed, and a static analysis of the tool is carried out. Time, costs, and risk of falling from height are compared with traditional methods (ladders, stilts, manual wheeled scaffolding, and motorized scaffolding). The tool incorporates a telescopic carbon fiber mast, a direct-current motor, and electromagnets. The results indicate that the tool is the second fastest method (4′38″) and has the second lowest cost (EUR 8026.93). It is concluded that it is a viable option for trellising, since it eliminates the risk of falling from height while maintaining competitive times and reasonable costs. Full article

Fibrosis, characterized by excessive extracellular matrix (ECM) deposition, disrupts tissue architecture and impairs organ function, ultimately leading to severe health consequences and even failure of vital organs such as the lung, heart, liver, and kidney. Despite significant advances in understanding the molecular mechanisms underlying fibrosis, effective therapeutic options remain limited. Emerging evidence highlights scaffold proteins as critical regulators in the progression of fibrosis. These multifunctional proteins serve as molecular platforms that organize and coordinate key signaling pathways—including those governing ECM remodeling, cytoskeletal organization, and cell migration—thereby integrating both profibrotic and antifibrotic signals. Their pivotal role in linking mechanotransduction, inflammatory, and developmental signals offers a unique therapeutic window, as targeted interventions (e.g., small-molecule inhibitors, peptides, biologics, and gene therapy) are emerging to modulate these pathways. This review synthesizes recent findings on scaffold protein functions across multiple organs and discusses novel therapeutic strategies to manage and potentially reverse fibrosis. Full article

Cartilage damage is common in sports injuries and cartilage-related diseases, such as degenerative joint and rheumatic disorders. Autologous chondrocyte implantation (ACI) is a widely used cell-based therapy for repairing cartilage damage in clinical practice. In this procedure, a patient’s chondrocytes are isolated, cultured in vitro to expand the cell population, and then implanted into the damaged site. However, in vitro expansion of chondrocytes on standard 2D culture surfaces leads to dedifferentiation (loss of the chondrocyte phenotype), and the delivery of detached cells has proven to be ineffective. To overcome these limitations, the matrix-assisted ACI (MACI) procedure was developed. In MACI, matrices such as hydrogels and microspheres are used as cell carriers or scaffolds to deliver expanded chondrocytes, enhancing cell viability and precision delivery. To streamline the two key steps of MACI—cell expansion and delivery—this study aims to investigate various configurations of gelatin-based hydrogels for their potential to support both cell expansion and delivery as a single step. This study evaluated gelatin microspheres (Gel MS), micronized photo-crosslinked GelMA microparticles (GelMA MP), and bulky GelMA hydrogels containing cells (GelMA HG). Cell growth, maintenance of the chondrocyte phenotype, and cartilage extracellular matrix (ECM) production were assessed in pellet cultures for cells grown on/in these carriers, compared with cells cultured on tissue culture-treated polystyrene (TCP). Our results demonstrate that normal human knee articular chondrocytes exhibit robust growth on Gel MS and form aggregates enriched with glycosaminoglycan-rich ECM. Gel MS outperformed both GelMA MP and GelMA HG as a cell carrier by both supporting long-term cell growth with reduced dedifferentiation and precision delivery. Full article

4(3H)-quinazolinone is a functional scaffold that exists widely both in natural products and synthetic organic compounds. Its drug-like derivatives have been extensively synthesized with interesting biological features including anticancer, anti-inflammatory, antiviral, antimalarial, antibacterial, antifungal, and herbicidal, etc. In this review, we highlight the medicinal and agrochemical versatility of the 4(3H)-quinazolinone scaffold according to the studies published in the past six years (2019–2024), and comprehensively give a summary of the target recognition, structure–activity relationship, and mechanism of its analogs. The present review is expected to provide valuable guidance for discovering novel lead compounds containing 4(3H)-quinazolinone moiety in both drug and agrochemical research. Full article

Periodontitis is accompanied by inflammation that causes dysregulation of the Wnt/β-catenin and TGF-β signaling pathways. This leads to a violation of the homeostasis of periodontal tissues. Components of the extracellular matrix (ECM) are an important part of biomaterials used for the repair of periodontal tissue. The purpose of this study was to evaluate the components of the effect of ECM (hyaluronic acid (HA), fibronectin (Fn), and laminin (Lam)) on the osteogenic and odontogenic differentiation of periodontal ligament stem cells (PDLSCs) in the collagen I hydrogel under conditions of disruption of the Wnt/β-catenin and TGF-β signaling pathways. The study showed that the addition of components of the ECM restored the expression of odontogenic markers in PDLSCs, which was absent during inhibition of the canonical Wnt signaling pathway, and their multidirectional effect on the secretion of transforming growth factor-β1 (TGF-β1) and bone morphogenetic protein 2 (BMP-2). Fn and Lam suppressed the expression of odontogenic markers in PDLSCs against the background of inhibition of the TGF-β signaling pathway. The addition of HA under the conditions of the TGF-β signaling pathway improved BMP-2 secretion, preserving odontogenic differentiation. Thus, our results demonstrated that disruption of the Wnt/β-catenin and TGF-β signaling pathways causes disorders in the differentiation of PDLSCs, preventing the regeneration of periodontal tissues. This should be taken into account when developing multicomponent scaffolds that recapitulate the ECM microenvironment at endogenic regeneration of the periodontium. Inclusion of hyaluronic acid as one of these components may enhance the therapeutic effect of such biomaterials. Full article

Bridge construction equipment (BCE) is crucial for efficiently executing large-scale infrastructure projects, particularly those involving continuous long-span bridges. Current BCE technologies, like the Overhead Movable Scaffolding System (OMSS), are often chosen for their high efficiency and cost-effective reusability. However, the lack of a standardised design framework tailored to Australian conditions complicates the design process, potentially leading to increased inefficiencies and safety concerns. This research project seeks to establish a novel design procedure for BCE, using the OMSS in Australia as a case study. The project adopts parametric design techniques using Rhinoceros (Rhino) 3D and Grasshopper to create a three-dimensional linear model. This model undergoes initial structural optimisation with Karamba3D. Subsequent advanced analyses include linear static design assessments performed in Strand7, a sophisticated finite element analysis software. The evaluation primarily utilises Australian standards to assess performance against various load types and combinations, such as permanent (dead), imposed (live), and wind loads. The structural integrity, including maximum displacement, axial forces, and bending moments, is manually verified against the analysis outcomes. The results confirm that the OMSS model adheres to ultimate and serviceability limit state requirements, affirming the effectiveness of the proposed design procedure for BCE. The research culminates in a design procedure flowchart and further suggests future research directions to refine BCE design methodologies for complex bridge construction scenarios. Full article

Myocardial infarction remains a leading cause of death worldwide due to the heart’s limited regenerative capability and the current lack of viable therapeutic solutions. Therefore, there is an urgent need to develop effective treatment options to restore cardiac function after a heart attack. Stem cell-derived cardiac cells have been extensively utilised in cardiac tissue regeneration studies. However, the use of Matrigel as a substrate for the culture and maturation of these cells has been a major limitation for the translation of this research into clinical application. Hydrogels are emerging as a promising system to overcome this problem. They are biocompatible and can provide stem cells with a supportive scaffold that mimics the extracellular matrix, which is essential for repairing damaged tissue in the myocardium after an infarction. Thus, hydrogels provide an alternative and reproducible option in addressing myocardial infarction due to their unique potential therapeutic benefits. This review explores the different types of natural and synthetic polymers used to create hydrogels and their various delivery methods, the most common being via injection and cardiac patches and other applications such as bioprinting. Many challenges remain before hydrogels can be used in a clinical setting, but they hold great promise for the future of cardiac tissue regeneration. Full article

Background/Objectives: Type 1 diabetes (T1D) is a chronic autoimmune condition characterized by the destruction of pancreatic β-cells, leading to insulin deficiency. Current therapies, such as islet transplantation, face significant challenges, including limited donor availability and the need for lifelong immunosuppression. Encapsulation technologies offer a promising alternative, providing immune protection and maintaining β-cell viability. In this study, we propose an encapsulation device featuring a spiral tubular semipermeable polyethersulfone (PES) membrane reinforced with a rigid biocompatible resin scaffold. Methods: The PES membrane was engineered with a tailored porosity of 0.5 µm, enabling efficient nutrient and oxygen exchange while preventing immune cell infiltration. Using INS-1E insulin-secreting cells aggregated into size-controlled islet-like spheroids (ILSs), we evaluated the device’s performance. Results: The device achieved high ILS viability and insulin secretion over 48 h at therapeutic densities, maintaining functionality comparable to free-floating ILSs (control). The PES membrane, with its mechanical stability and biocompatibility, ensured durability without compromising diffusion dynamics, overcoming a critical limitation of other encapsulation approaches. Importantly, the device geometry allowed for the encapsulation of up to 356,000 islet equivalents (IEQs) in a single capillary fiber, reaching therapeutic thresholds for T1D patients. Conclusions: this device, with its innovative design, enables high-density encapsulation while preserving ILS functionality and scalability, making it a potential platform for clinical application. This work highlights the potential of PES-based encapsulation devices to overcome key barriers in T1D treatment, paving the way for personalized, long-term solutions to restore insulin independence. Full article

BCR-ABL1 kinase is a critical driver of chronic myeloid leukemia (CML) pathophysiology. The approval of allosteric inhibitor asciminib brings new hope for overcoming drug resistance caused by mutations in the ATP-binding site. To expand the chemical diversity of BCR-ABL1 kinase inhibitors with positive anti-tumor effect with asciminib, structure-based virtual screening and molecular dynamics simulations were employed to discover novel scaffolds. This approach led to the identification of a series of N-(2-acetamidobenzo[d]thiazol-6-yl)-2-phenoxyacetamide derivatives as new BCR-ABL1 inhibitors. The most potent compound, 10m, demonstrated inhibition of BCR-ABL-dependent signaling and showed an anti-tumor effect against K562 cells, with an IC₅₀ value of 0.98 μM. Compound 10m displayed powerful synergistic anti-proliferation and pro-apoptotic effects when combined with asciminib, highlighting its potential as a promising lead for the development of potential BCR-ABL inhibitors. Full article