Search Results (75)

Nucleopeptides (NPs) are unnatural hybrid polymers designed by coupling nucleobases to the side chains of amino acid residues within peptides. In this study, we present the synthesis of an Fmoc-protected nucleobase amino acid (NBA) monomer (Fmoc-1,4-TzlNBA_A) with adenine attached to the side chain of L-homoazidoalanine (Aha) through a 1,4-linked-1,2,3-triazole. The coupling was accomplished by a Cu(I)-catalyzed azide–alkyne cycloaddition (CuAAC) of Fmoc-Aha and N9-propargyladenine. Subsequently, a homotrinucleopeptide (HalTzl_AAA) containing three 1,4-TzlNBA_A residues was synthesized, using different solid-phase peptide synthesis (SPPS) approaches, and its ability to recognize U-rich motifs of RNAs involved in the HIV replication cycle was studied using circular dichroism (CD) and fluorescence spectroscopy. CD curves confirmed the binding of HalTzl_AAA to U-rich motifs of the transactivation responsive element (TAR UUU RNA HIV-1) bulge and the anticodon stem–loop domain of human tRNALys3 (ASLLys3) by a decrease in the positive ellipticity band intensity around 265 nm during the complexation. 5′-(FAM(6))-labeled TAR UUU and hASLLys3 were used for fluorescence anisotropy binding studies. Fluorescence data revealed that HalTzl_AAA bound TAR’s UUU bulge with a moderate affinity (K_d ≈ 38 µM), whereas the ASLLys3 UUUU-containing loop sequence was recognized with 2.5 times lower affinity (with K_d ≈ 75 µM). Both the standard SPPS method and its variants, which involved the attachment of adenine to the L-Aha side chain using the click reaction during the synthesis on the resin or after the nucleopeptide cleavage, were characterized by a similar efficiency and yield. The CD and fluorescence results demonstrated that HalTzl_AAA recognized the U-rich sequences of the RNAs with moderate and varied affinities. It is likely that both the hydrogen bonds associated with the complementarity of the interacting sequences and the conformational aspects associated with the high conformational dynamics of U-rich motifs are important in the recognition process. The nucleopeptide represents a new class of RNA binders and may be a promising scaffold for the development of new antiviral drugs. Full article

In this study, bio-based polyurethanes (PUs) were synthesized using renewable polyols derived from sunflower seed oil, aiming to develop flexible yet robust polymeric films and scaffolds. Given their composition and favorable physico-chemical properties, these materials may represent promising candidates for the design and development of advanced biomedical systems. Two distinct oil polyols were prepared via glycerol transesterification (GM) and epoxidation (EPO) with hydrogen peroxide/glacial acetic acid, respectively. These polyols, in combination with poly(tetramethylene ether) glycol (PTMEG) and/or poly(ethylene glycol) (PEG), served as diol components in a one-step reaction with 1,6-hexamethylene diisocyanate (HDI). The structure of the polyol precursors was thoroughly characterized by MALDI-TOF MS and NMR spectroscopy, confirming successful functionalization. The resulting PU films exhibited excellent flexibility (885%) and mechanical properties (23 MPa), as evaluated by ATR-FTIR, Tensile test, DSC, DMA and SEM methods. The crosslink density of the order of 10⁻³ also contributes to the development of outstanding mechanical properties. Stress relaxation experiments were described using a stretched exponential (Kohlrausch–Williams–Watts) model to capture the viscoelastic behavior of the materials. In addition, stress vs. relative elongation curves revealing strain-hardening behavior were also analyzed and modeled mathematically to better describe the mechanical response under deformation. Furthermore, salt leaching techniques were employed to fabricate porous scaffolds. This work highlights the versatility of vegetable oil-based feedstocks in producing functional polyurethanes with tunable mechanical properties for applied polymer systems. Full article

We propose Federated Entropic High-Order Descent (FedEHD), a drop-in client optimizer that augments local SGD with (i) an entropy (sign) term and (ii) quadratic and cubic gradient components for drift control and implicit clipping. Across non-IID CIFAR-10 and CIFAR-100 benchmarks (100 clients, 10% sampled per round), FedEHD achieves faster and higher convergence than strong baselines including FedAvg, FedProx, SCAFFOLD, FedDyn, MOON, and FedAdam. On CIFAR-10, it reaches 70% accuracy in approximately 80 rounds (versus 100 for MOON and 130 for SCAFFOLD) and attains a final accuracy of 72.5%. On CIFAR-100, FedEHD surpasses 60% accuracy by about 150 rounds (compared with 250 for MOON and 300 for SCAFFOLD) and achieves a final accuracy of 68.0%. In an environmental monitoring case study involving four distributed air-quality stations, FedEHD yields the highest macro AUC/F1 and improved calibration (ECE 0.183 versus 0.186–0.210 for competing federated methods) without additional communication and with only $\mathcal{O}(d)$ local overhead. The method further provides scale-invariant coefficients with optional automatic adaptation, theoretical guarantees for surrogate descent and drift reduction, and convergence curves that illustrate smooth and stable learning dynamics. Full article

Scaffolds are temporary structures that workers usually use during building or repair work. These structures can be built in different shapes and types depending on the type of joints to which the beams and columns of the scaffolds are connected. Due to their temporary nature, they are very sensitive to vibration under dynamic or static actions, and this causes many accidents and unstable behaviours in them. This unstable behaviour has different reasons, including bracing conditions and slenderness of the columns, stiffness of joints and anchors, imperfections in the construction, damage and corrosion due to climate change, etc. This article aims to reanalyse the mechanical properties of scaffold joints and anchors and obtain some critical factors in the overall stability of the mentioned structures, including load-bearing capacity, initial stiffness, energy absorption, and ductility. To this aim, some recent research on scaffolds has been summarised and discussed, and then the failure mode and mechanical behaviour of the scaffolds in different types of scaffold joints and anchors have been estimated and considered from previous studies. Moreover, some mechanical properties, including ductility, initial stiffness, and energy absorption, have been estimated and developed based on the force-displacement curves of previous studies. The results highlight the crucial importance of the mechanical properties and behaviour of anchors and joints in estimating the behaviour and stability of scaffolds. The results also revealed that determining the mechanical characteristics of the mentioned elements can have a significant influence on the optimisation and design of scaffolds more accurately and predictably. Moreover, determining the mechanical properties of the anchors and joints can enhance our insights and understanding of how the mentioned parameters can improve the behaviour, stability, and safety of the scaffold structures. Full article

Additive manufacturing technology, specifically material extrusion, offers great potential for scaffold manufacturing in tissue engineering. This study presents a novel methodology for the design and optimization of 3D printed polymeric scaffolds to enhance cell viability, thereby promoting improved cell proliferation for tissue engineering applications. Different infill patterns, including gyroid, parallel sinusoidal, and symmetric sinusoidal, were evaluated to determine their impact on cell proliferation and tissue regeneration. To overcome the limitations of existing slicer software, a novel open-source software called FullControl GCode Designer was utilized, enabling the creation of customized infill patterns without restrictions. VOLCO software was employed to generate voxelized 3D models of the scaffolds, simulating the material extrusion process. Finite element analysis was conducted using Abaqus software to evaluate the mechanical properties of the different designs. Additionally, new scripts were developed to evaluate the interconnectivity and pore size of the voxelized models. A factorial design of experiments and a genetic algorithm (combined with Kriging metamodels) were applied to identify the optimal configuration based on optimization criteria (keeping the mechanical stiffness and pore size within the recommended values for trabecular bone and maximizing the surface and interconnectivity). Biological testing was conducted on polylactic acid scaffolds to preliminarily validate the effectiveness of the modeling and optimization methodologies in this regard. The results demonstrated the agreement between the optimization methodology and the biological test since the optimum in both cases was a symmetric sinusoidal pattern design with a configuration resulting in a structure with 53.08% porosity and an equivalent pore size of 584 µm. Therefore, this outcome validates the proposed methodologies, emphasizing the role of pore surface area and interconnectivity in supporting cell proliferation. Overall, this research contributes to the advancement of AM technology in tissue engineering and paves the way for further optimization studies in scaffold design. Full article

Perfusable microvasculature is critical for advancing in vitro tissue models, particularly for neural applications where limited diffusion impairs organoid growth and fails to replicate neurovascular function. This study presents a versatile fabrication platform that integrates mesh-driven design, two-photon lithography (TPL), and modular interfacing to create multi-material, perfusable 3D microvasculatures. Various 2D and 3D capillary paths were test-printed using both polygonal and lattice support strategies. A double-layered capillary scaffold based on the Hilbert curve was used for comparative materials testing. Methods for printing rigid (OrmoComp), moderately stiff hydrogel (polyethylene glycol diacrylate, PEGDA 700), and soft elastomeric (photocurable polydimethylsiloxane, PDMS) materials were developed and evaluated. Cone support structures enabled high-fidelity printing of the softer materials. A compact heat-shrink tubing interface provided leak-free perfusion without bulky fittings. Physiologically relevant flow velocities and Dextran diffusion through the scaffold were successfully demonstrated. Cytocompatibility assays confirmed that all TPL-printed scaffold materials supported human neural stem cell viability. Among peripheral components, lids fabricated via fused deposition modeling designed to hold microfluidic needle adapters exhibited good biocompatibility, while those made using liquid crystal display-based photopolymerization showed significant cytotoxicity despite indirect exposure. Overall, this platform enables creation of multi-material microvascular systems facilitated by TPL technology for complex, 3D neurovascular modeling, blood–brain barrier studies, and integration into vascularized organ-on-chip applications. Full article

Background: Human African trypanosomiasis (HAT), caused by Trypanosoma brucei, is a neglected tropical disease with limited treatments, highlighting the pressing need for new drugs. Cell division cycle-2-related kinase 12 (CRK12), a pivotal protein involved in the cell cycle regulation of T. brucei, has emerged as a promising therapeutic target for HAT, yet effective CRK12 inhibitors remain lacking. Methods: An integrated strategy combining computational modeling, virtual screening, molecular dynamics (MD) simulations, and experimental validation was adopted to discover potential inhibitors against CRK12. By using the predicted and refined 3D structure of CRK12 from AlphaFold2 and MD simulation, over 1.5 million compounds were screened based on multiple-scale molecular docking, and 26 compounds were selected for evaluation of biological activity based on anti-T. brucei bioassays. Dose–response curves were generated for the most potent inhibitors, and the interaction mechanism between the top four compounds and CRK12 was explored by MD simulations and MM/GBSA binding free energy analysis. Results: Of the 26 compounds, six compounds demonstrated sub-micromolar to low-micromolar IC₅₀ values (0.85–3.50 µM). The top four hits, F733-0072, F733-0407, L368-0556, and L439-0038, exhibited IC₅₀ values of 1.11, 1.97, 0.85, and 1.66 µM, respectively. Binding free energy and energy decomposition analyses identified ILE335, VAL343, PHE430, ALA433, and LEU482 as hotspot residues for compound binding. Hydrogen bonding analysis demonstrated that these compounds can form stable hydrogen bonds with the hinge residue ALA433, ensuring their stable binding within the active site. Conclusions: This study establishes a robust and cost-effective pipeline for CRK12 inhibitor discovery, identifying several novel inhibitors demonstrating promising anti-HAT activity. The newly discovered scaffolds exhibit structural diversity distinct from known CRK12 inhibitors, providing valuable lead compounds for anti-trypanosomal drug development. Full article

Background/Objective: This study aimed to develop a predictive model to classify and rank highly active compounds that inhibit HIV-1 integrase (IN). Methods: A total of 2271 potential HIV-1 inhibitors were selected from the ChEMBL database. The most relevant molecular descriptors were identified using a hybrid GA-SVM-RFE approach. Predictive models were built using Random Forest (RF), eXtreme Gradient Boosting (XGBoost), Support Vector Machines (SVM), and Multi-Layer Perceptron (MLP). The models underwent a comprehensive evaluation employing calibration, Y-randomization, and Net Gain methodologies. Results: The four models demonstrated intense calibration, achieving an accuracy greater than 0.88 and an area under the curve (AUC) exceeding 0.90. Net Gain at a high probability threshold indicates that the models are both effective and highly selective, ensuring more reliable predictions with greater confidence. Additionally, we combine the predictions of multiple individual models by using majority voting to determine the final prediction for each compound. The Rank Score (weighted sum) serves as a confidence indicator for the consensus prediction, with the majority of highly active compounds identified through high scores in both the 2D descriptors and ECFP4-based models, highlighting the models’ effectiveness in predicting potent inhibitors. Furthermore, cluster analysis identified significant classes associated with vigorous biological activity. Conclusions: Some clusters were found to be enriched in highly potent compounds while maintaining moderate scaffold diversity, making them promising candidates for exploring unique chemical spaces and identifying novel lead compounds. Overall, this study provides valuable insights into predicting integrase binders, thereby enhancing the accuracy of predictive models. Full article

Over the past two decades, additive manufacturing has advanced significantly, enabling rapid fabrication of functional components across various applications. In medical devices, it has been used for prototyping, prosthetics, drug delivery platforms, and more recently, tissue scaffolding. However, current technologies face challenges, particularly in depositing conformal layers over curved surfaces. This study introduces a novel multi-nozzle extrusion printer concept designed to deposit soft gel layers onto curved surfaces. A custom clearance locking mechanism enhances the printer’s ability to achieve conformal coatings on both flat and curved substrates. We investigate key deposition parameters, including displacement volume and nozzle configuration, while comparing two deposition sequences: “Press and Express” and “Express and Press”. Our results demonstrate that the “Express and Press” technique yields more uniform, merged conformal layers than the “Press and Express” method. This technology holds promise for further refinement and potential applications in tissue engineering. Full article

The increasing reliance on digital tools in architectural education has transformed design workflows, offering new opportunities for creativity while posing challenges to students’ logical reasoning and structured problem-solving abilities. While digital tools facilitate automation and generative design, over-reliance on them can limit students’ ability to navigate design complexity independently. Addressing this issue, this study develops the Logic-Driven and Technology-Supported Creativity Development Model to examine the roles of logical frameworks, digital tools, and open-ended design tasks in fostering structured creativity. The findings reveal that logical frameworks provide essential cognitive scaffolding, helping students balance creative exploration with structured decision-making. Digital tools enhance form generation but introduce challenges such as automation bias and steep learning curves. Open-ended tasks promote design flexibility, yet their effectiveness depends on logical structures to maintain coherence. This study highlights the importance of curriculum design in supporting structured creativity, emphasizing the integration of technical training, interdisciplinary methods, and reflective learning. The findings contribute to design education theory and provide practical insights for improving course structures and pedagogical approaches in digital design environments. Full article

This study presents experimental investigations of the flexural bearing capacity of the lower load-bearing structures of pull-up cantilever scaffolds with adjustable steel tie rods. First, load-bearing structures with three different specifications are tested to analyze their primary failure modes and failure mechanisms. The experimental results are then simulated and validated using a finite element analysis (FEA) method. Subsequently, an extended parametric analysis is performed numerically, and a simplified calculation formula is derived through nonlinear curve fitting to evaluate the load-bearing capacity. Finally, the effects of the transverse spacing of the vertical rods, the length of the cantilever beams, and the spacing of the hanging ears on the flexural bearing capacity of the structures are analyzed. Full article

This study investigated the buckling behaviour of the scaffold independent supporting system considering semi-rigid nodes. Firstly, a scaffold independent supporting system without the horizontal and diagonal braces in the middle or/and bottom parts of the columns was proposed. The scaffold independent supporting system consisted of horizontal beams located under concrete formwork, upright columns, and beam–column nodes. There was a lot of free space within the scaffold independent supporting system, which made it possible to conduct other operational work during the curing of concrete. Then, using numerical simulation, the rotation stiffness of the beam–column node was calculated as 37.18 kN·m/rad. According to the normalized moment–rotation curve, the beam–column node was assessed as a semi-rigid node. Finally, a numerical simulation method was proposed to analyse the buckling behaviour and determine the effective length factor of the scaffold independent supporting system, in which the semi-rigid connection was characterized by setting the spring elements on the beam–column node. The results indicate that the column space and column height have effects on the effective length factor of the scaffold independent supporting system. The effective length factor increased with the increase in the column space, whereas it decreased with the increase in the column height. In addition, the initial imperfection had no obvious effects on the effective length factor. Full article

This study investigates the design and mechanical evaluation of hydroxyapatite (HAp) scaffolds for bone tissue engineering, using stereolithography (SLA) to fabricate homogeneous and hollow elongated Voronoi structures. HAp, known for its biocompatibility and biodegradability, was selected to create scaffolds with a structure that supports cell growth. Both scaffold designs were tested under compression to measure key properties, including compressive strength, Young’s modulus, stiffness, and energy absorption. The homogeneous design demonstrated superior mechanical properties, achieving a maximum load of 913.6 N at a displacement of 0.166 mm and a stiffness of 5162.8 N/mm, indicating a higher load-bearing capacity and energy absorption compared to the hollow design. Despite these strengths, failure analysis revealed early fractures at strut junctions, particularly in slender areas, leading to fluctuations in the load–displacement curve and suggesting a risk to neighboring tissues in practical applications. These findings underscore the potential of Voronoi-based scaffolds for orthopedic use, while also highlighting the need for structural refinements to improve scaffold durability and clinical effectiveness. Full article

Hyperthermia is nowadays intensively investigated as a promising strategy to improve the therapeutic efficacy against different types of cancer and resistant infections. In particular, the remote generation of localized hyperthermia by magnetic field through iron-oxide nanoparticles (IONPs) offers good thermal conductivity in a controlled area. The incorporation of these IONPs in 3D-printed scaffolds designed for bone tissue regeneration has been scarcely addressed in the literature. This strategy would add the potential of magnetic-mediated hyperthermia against remnant cancer or resistant infections in the damaged tissue area to these personalized bone-related scaffolds. The present work proposes two methodologies to obtain 3D-printed bone-related scaffolds with magnetic properties: 1-Direct 3D printing with IONPs-embedded polylactic acid (PLA) and hydroxyapatite (HA), resulting in a uniform distribution of IONPs; and 2-Drop coating on 3D-printed PLA/HA scaffolds, resulting in the IONPs being concentrated on the scaffold surface. Physicochemical/mechanical characterizations were performed to confirm the IONPs’ distributions and viability assays were carried out to validate the absence of cytotoxicity. Hyperthermia tests (314 kHz) were carried out, including the simulation/validation of the experimental equipment, to establish optimal distances from the planar coil. Temperature–time/distance curves were obtained and parametrized (R² > 0.96) for both methodologies in relation to the contribution of IONPs (0.20–1.00 mg), their distribution in the scaffold (uniform/concentrated), the electric-current intensity, and the distance. The results validated both methodologies to obtain personalized 3D-printed PLA/HA scaffolds with magnetic properties, reaching the required moderate/ablative hyperthermia levels. Full article

Due to their nature, using shear thickening fluids (STFs) in engineering applications has sparked an interest in developing energy-dissipating systems, such as damping devices or shock absorbers. The Rheinforce technology allows the design of customized energy dissipative composites by embedding microfluidic channels filled with STFs in a scaffold material. One of the reasons for using microfluidic channels is that their shape can be numerically optimized to control pressure drop (also known as rectifiers); thus, by controlling the pressure drop, it is possible to control the energy dissipated by the viscous effect. Upon impact, the fluid is forced to flow through the microchannel, experiencing the typical entry flow until it reaches the fully developed flow. It is well-known for Newtonian fluid that the entrance flow is responsible for a non-negligible percentage of the total pressure drop in the fluid; therefore, an analysis of the fluid flow at the entry region for STFs is of paramount importance for an accurate design of the Rheinforce composites. This analysis has been numerically performed before for shear-thickening fluids modeled by a power-law model; however, as this constitutive model represents a continuously growing viscosity between end-viscosity plateau values, it is not representative of the characteristic viscosity curve of shear-thickening fluids, which typically exhibit a three-region shape (thinning-thickening-thinning). For the first time, the influence of these three regions on the entry flow on an axisymmetric pipe is analyzed. Two-dimensional numerical simulations have been performed for four STFs consisting of four dispersions of fumed silica nanoparticles in polypropylene glycol varying concentrations (7.5–20 wt%). Full article