Search Results (2,995)

In this study, 3-trimethoxy-silylpropane-1-thiol (MPTMS) was used as a surface modifier for Al₂O₃ powder to systematically analyze the effects of MPTMS concentration on the rheological properties, photocuring characteristics, and 3D printing performance of photocurable composite slurries. MPTMS concentration significantly influenced the rheological behavior of the slurry. Slurries containing 2 wt.% and 5 wt.% MPTMS exhibited a wide linear viscoelastic range (LVR). However, at concentrations of 10 wt.% and 20 wt.%, the LVR range narrowed, which led to reduced dispersion stability. In dispersion stability tests, the slurry with 2 wt.% MPTMS showed the most stable dispersion, while the 5 wt.% MPTMS concentration exhibited the highest photocuring rate. In 3D printing experiments, the 5 wt.% MPTMS concentration resulted in the most stable printed structures, whereas printing failures occurred with the 2 wt.% concentration. At 10 wt.% and 20 wt.%, internal cracking was observed, leading to structural defects. In conclusion, MPTMS forms silane bonds on the Al₂O₃ surface, significantly impacting the stability, rheological properties, and printing quality of Al₂O₃-acrylate composite slurries. An MPTMS concentration of 5 wt.% was found to be optimal, contributing to the formation of stable and robust structures. Full article

Large osseous defects resulting from trauma, tumor resection, or fracture render the inherent ability of the body to repair inadequate and necessitate the use of bone grafts to facilitate the recovery of both form and function of the bony defect sites. In the United States alone, a large number of bone graft procedures are performed yearly, making it an essential area of investigation and research. Synthetic grafts represent a potential alterative to autografts due to their patient-specific customizability, but currently lack widespread acceptance in the clinical space. Early in their development, non-autologous bone grafts composed of metals such as stainless steel and titanium alloys were favorable due to their biocompatibility, resistance to corrosion, mechanical strength, and durability. However, since their inception, bioceramics have also evolved as viable alternatives. This review aims to present an overview of the fundamental prerequisites for tissue engineering devices using bioceramics as well as to provide a comprehensive account of their historical usage and significant advancements over time. This review includes a summary of commonly used manufacturing techniques and an evaluation of their use as drug carriers and bioactive coatings—for therapeutic ion/drug release, and potential avenues to further enhance hard tissue regeneration. Full article

The limited capacity of articular cartilage for self-repair is a critical challenge in orthopedic medicine. Here, we aimed to develop a simplified method of generating chondrocyte particles from human-induced pluripotent stem cell-derived expandable limb-bud mesenchymal cells (ExpLBM) using a cell self-aggregation technique (CAT). ExpLBM cells were induced to form chondrocyte particles through a stepwise differentiation protocol performed on a CAT plate (prevelex-CAT^®), which enables efficient and consistent production of an arbitrary number of uniformly sized particles. Histological and immunohistochemical analyses confirmed that the generated chondrocyte particles expressed key cartilage markers, such as type II collagen and aggrecan, but not hypertrophic markers, such as type X collagen. Additionally, when these particles were transplanted into osteochondral defects in rats with X-linked severe combined immunodeficiency, they demonstrated successful engraftment and extracellular matrix production, as evidenced by Safranin O and Toluidine Blue staining. These data suggest that the plate-based CAT system offers a robust and scalable approach to produce a large number of chondrocyte particles in a simplified and efficient manner, with potential application to cartilage regeneration. Future studies will focus on refining the system and exploring its clinical applications to the treatment of cartilage defects. Full article

Background/Objectives: Mitochondria are the main organelles for ATP synthesis able to produce energy for several different cellular activities. Cardiac cells require high amounts of energy and, thus, they contain a high number of mitochondria. Consequently, mitochondrial dysfunction in these cells is a crucial factor for the development of cardiovascular diseases. Mitochondria constitute central regulators of cellular metabolism and energy production, producing approximately 90% of the cells’ energy needs in the form of ATP via oxidative phosphorylation. The mitochondria have their own circular, double-stranded DNA encoding 37 genes. Any mitochondrial DNA sequence anomaly may result in defective oxidative phosphorylation and lead to cardiac dysfunction. Methods: In this study, we investigated the potential association between mitochondrial DNA mutation and cardiovascular disease. Cardiac tissue and serum samples were collected from seven patients undergoing coronary artery bypass grafting. Total DNA was extracted from cardiac muscle tissue specimens and serum and each sample was subjected to polymerase chain reaction (PCR) to amplify the NADH dehydrogenase 1 (ND1) gene, which is part of the mitochondrial complex I enzyme complex and was screened for mutations. Results: We identified one patient with a homoplasmic A to G substitution mutation in cardiac tissue DNA and two patients with heteroplasmic A3397G mutation in serum DNA. Specifically, amplicon sequence analysis revealed a homoplasmic A3397G substitution in the ND1 gene in a tissue sample of the patient with ID number 1 and a heteroplasmic mutation in A3397G in serum samples of patients with ID numbers 3 and 6, respectively. The A to G substitution changes the amino acid from methionine (ATA) to valine (GTA) at position 31 of the ND1 gene. Conclusions: The detection of this novel mutation in patients with coronary artery disease may contribute to our understanding of the association between mitochondrial dysfunction and the disease, implying that mitochondria may be key players in the pathogenesis of cardiovascular diseases. Full article

Congenital heart diseases (CHDs) are a group of complex diseases characterized by structural and functional malformations during development in the human heart; they represent an important problem for public health worldwide. Within these malformations, septal defects such as ventricular (VSD) and atrial septal defects (ASD) are the most common forms of CHDs. Studies have reported that CHDs are the result of genetic and environmental factors. Here, we review and summarize the role of genetics involved in cardiogenesis and congenital cardiac septal defects. Moreover, treatment regarding these congenital cardiac septal defects is also addressed. Full article

Molding injects a molding compound into a mold to form a protective shell around the wafer. During the injection process, overflow may occur, leading to mold flash, which reduces yield and causes significant manufacturing cost losses. This paper proposes a deep-learning-based method for detecting and predicting the occurrence of mold flash probability to address this issue. First, the paper conducts random forest importance analysis and correlation analysis to identify the key parameters that significantly impact mold flash. This paper uses these key parameters as input signals for the prediction model. The paper introduces an HLGA Transformer to construct an ensemble meta-learning model that predicts the probability of molding defects, achieving a prediction accuracy of 98.16%. The ensemble meta-learning approach proposed in this paper outperforms other methods in terms of performance. The model predictions can be communicated to the system in real time, allowing it to promptly adjust critical machine operation parameters, thereby significantly improving the molding process yield and reducing substantial manufacturing cost losses. Full article

Store-operated Ca²⁺ entry (SOCE) controls Ca²⁺ homeostasis and mediates multiple Ca²⁺-dependent signaling pathways and cellular processes. It relies on the concerted activity of the reticular Ca²⁺ sensor STIM1 and the plasma membrane Ca²⁺ channel ORAI1. STIM1 and ORAI1 gain-of-function (GoF) mutations induce SOCE overactivity and excessive Ca²⁺ influx, leading to tubular aggregate myopathy (TAM) and Stormorken syndrome (STRMK), two overlapping disorders characterized by muscle weakness and a variable occurrence of multi-systemic anomalies affecting spleen, skin, and platelets. To date, different STIM1 mouse models exist, but only a single ORAI1 mouse model with muscle-specific TAM/STRMK phenotype has been described, precluding a comparative analysis of the physiopathology in all affected tissues. Here, we generated and characterized mice harboring a prevalent ORAI1 TAM/STRMK mutation and we provide phenotypic, physiological, biochemical, and functional data. Examination of Orai1^V109M/+ mice revealed smaller size, spleen enlargement, reduced muscle force, and decreased platelet numbers. Morphological analyses of muscle sections evidenced the presence of tubular aggregates, the histopathological hallmark on biopsies from TAM/STRMK patients absent in all reported STIM1 models. Overall, Orai1^V109M/+ mice reliably recapitulate the human disorder and highlight the primary physiological defects caused by ORAI1 gain-of-function mutations. They also provide the possibility to investigate the formation of tubular aggregates and to develop a common therapy for different TAM/STRMK forms. Full article

Wire Electric Discharge Machining (WEDM) is an unconventional machining technology that uses electrical impulses to generate very high temperatures to cut material. The WEDM process hence causes some unfortunate defects, such as cracks and burnt cavities, which can impact the correct functionality of the machined pieces and shorten their service life. This study was carried out to understand which materials remain defect-free after WEDM. The examined materials were the Ampcoloy 35 copper alloy, the high-entropy steels FeCoCrMnNi and FeCoCrMnNiC_0.2, and the B1914 and Nimonic 263 nickel alloys. The influence of the machining parameters, namely the pulse off time, gap voltage, discharge current, pulse on time, and wire feed, on the cutting speed and the surface topography of the machined piece was investigated. The surface morphology, the state of the subsurface layer in a cross-section, and the number of diffused elements from the wire electrode were analysed. All the analysed materials were found completely suitable for WEDM machining as they do not form any surface or subsurface defects. Full article

Hemoglobinopathies, namely β-thalassemia and sickle cell disease (SCD), are hereditary diseases, characterized by molecular genetic aberrations in the beta chains of hemoglobin. These defects affect the normal production of hemoglobin with severe anemia due to less or no amount of beta globins in patients with β-thalassemia (quantitative disorder), while SCD is a serious disease in which a mutated form of hemoglobin distorts the red blood cells into a crescent shape at low oxygen levels (qualitative disorder). Despite the revolutionary progress in recent years with the approval of gene therapy and gene editing for specific patients, there is an unmet need for highlighting the mechanisms influencing hemoglobin production and for the development of novel drugs and targeted therapies. The identification of the transcription factors and other genetic modifiers of hemoglobin expression is of utmost importance for discovering novel therapeutic approaches for patients with hemoglobinopathies. The aim of this review is to describe these complex molecular mechanisms and pathways affecting hemoglobin expression and to highlight the relevant investigational approaches or pharmaceutical interventions focusing on restoring the hemoglobin normal function by linking the molecular background of the disease with the clinical perspective. All the associated drugs increasing the hemoglobin expression in patients with hemoglobinopathies, along with gene therapy and gene editing, are also discussed. Full article

In this paper, the microstructure and mechanical properties at the interface of Incoloy825/X65 bimetallic composite pipe achieved by explosive welding were systematically studied. Results show that a periodic wavy bonding interface was formed between the Incoloy825 and X65 due to the jets caused by the high-impact stresses during explosive welding, which was beneficial for improving the bonding strength of the Incoloy825 and X65. Atomic diffusion and localized melting occurred near the interface during explosive welding. Some fine crystal grains were generated in the vicinity of the interface due to the strong plastic deformation and dynamic recrystallization, whereas some elongated grains growing in the perpendicular direction to the interface were found in the wider localized melted zone. Room temperature nanoindentation test showed that due to the existence of fine grains resulting from the recrystallization at the interface, the hardness of the interface was higher than that of the base metals. Voids and defects were prone to appearing in the vortex regions near the interface, where the weak point in the interface was located. Full article

Incremental sheet forming has emerged as an excellent alternative to other material forming procedures, incrementally deforming flat metal sheets into complex three-dimensional profiles. The main characteristics of this process are its versatility and cost-effectiveness; additionally, it allows for greater formability compared to conventional sheet forming processes. Recently, its application has been extended to polymers and composites. The following review aims to present the current state of the art in the incremental sheet forming of polycarbonate, an outstanding engineering plastic, beginning with initial studies on the feasibility of this process for polymers. Attention is given to the advantages, drawbacks, and main applications of incrementally formed polycarbonate sheets, as well as the influence of process parameters and toolpath strategies on features such as formability, forming forces, deformation and failure mechanisms, geometric accuracy, surface quality, etc. Additionally, new hybrid forming methods for process optimisation are presented. Finally, a discussion is provided on the technical challenges and future research directions for incremental sheet forming of polycarbonate and, more generally, thermoplastics. Thus, this review aims to offer an extensive overview of the incremental forming of polycarbonate sheets, useful to both academic and industrial researchers working on this topic. Full article

One of the technological hurdles in the widespread application of additive manufacturing is the formation of undesired microstructure and defects, e.g., the formation of columnar grains in Ti-6Al-4V—the columnar microstructure results in anisotropic mechanical properties, a reduction in ductility, and a decrease in the endurance limit. Here, we present the potential implementation of a hexagonal array of synchronized lasers to alter the microstructure of Ti–6Al–4V toward the formation of preferable equiaxed grains. An anisotropic heat transfer model is employed to obtain the temporal/spatial temperature distributions and construct the solidification map for various process parameters, i.e., laser power, scanning speed, and the internal distance among lasers in the array. Approximately 55% of the volume fraction of equiaxed grains is obtained using a laser power of P = 500 W and a scanning speed of v = 100 mm/s. The volume fraction of the equiaxed grains decreases with increasing scanning velocity; it drops to 38% for v = 1000 mm/s. This reduction is attributed to the decrease in absorbed heat and thermal crosstalk among lasers, i.e., the absorbed heat is higher at low scanning speeds, promoting thermal crosstalk between melt pools and subsequently forming a large volume fraction of equiaxed grains. Additionally, a degree of overlap between lasers in the array is required for high scanning speeds (v = 1000 mm/s) to form a coherent melt pool, although this is unnecessary for low scanning speeds (v = 100 mm/s). Full article

This study investigated the effects of incorporating reduced-graphene-oxide-coated alumina (Al₂O₃–RGO) nanoparticles and unmodified graphene oxide (GO) onto the microstructure as well as the mechanical properties of Al₂O₃/TiB₂ matrix ceramic materials. The microstructure observation revealed that, compared with GO addition, the addition of Al₂O₃–RGO nanoparticles significantly improved RGO dispersion in the ceramic materials and reduced defects such as pores caused by graphene agglomeration. In addition, the uniformly dispersed RGO nanosheets were interwoven with each other to form a three-dimensional grid structure due to grain growth and the disappearance of pores during sintering, which increased the contact area and interface-bonding strength between the RGO and ceramic matrix. According to the results of microstructure observation and analysis, the good interfacial strength not only facilitated load transfer from the ceramic matrix to the RGO but also induced the fracture mechanism of the RGO, which consumes more fracture energy than the traditional toughening mechanism. The results of mechanical properties analysis showed that the hardness, flexural strength, and fracture toughness of the obtained ATB–RG3.0 ceramic material was measured at 19.52 GPa, 1063.52 MPa, and 9.16 MPa·m1/2, respectively. These values are 16.82%, 27.92%, and 26.87% higher than those of the ceramic material with 3.0 vol.% GO. Full article

The diffusional dynamics and vibrational spectroscopy of molecular hydrogen (H₂) in myoglobin (Mb) is characterized. Hydrogen has been implicated in a number of physiologically relevant processes, including cellular aging or inflammation. Here, the internal diffusion through the protein matrix was characterized, and the vibrational spectroscopy was investigated using conventional empirical energy functions and improved models able to describe higher-order electrostatic moments of the ligand. Depending on the energy function used, H₂ can occupy the same internal defects as already found for Xe or CO (Xe1 to Xe4 and B-state). Furthermore, four additional sites were found, some of which had been discovered in earlier simulation studies. Simulations using a model based on a Morse oscillator and distributed charges to correctly describe the molecular quadrupole moment of H₂ indicate that the vibrational spectroscopy of the ligand depends on the docking site it occupies. This is consistent with the findings for CO in Mb from experiments and simulations. For H₂, the maxima of the absorption spectra cover ∼20 cm⁻¹ which are indicative of a pronounced Stark effect of the surrounding protein matrix on the vibrational spectroscopy of the ligand. Electronic structure calculations show that H₂ forms a stable complex with the heme iron (stabilized by ∼−12 kcal/mol), but splitting of H₂ is unlikely due to a high activation energy (∼50 kcal/mol). Full article

The current strategy for treating osteomyelitis includes surgical procedures for complete debridement of the formed biofilm and necrotic tissues, systemic and oral antibiotic therapy, and the clinical use of cements and three-dimensional scaffolds as bone defect fillers and delivery systems for therapeutic agents. The aim of our research was to formulate a low-cost hybrid nanoparticulate biomaterial using poly(lactic-co-glycolic acid) (PLGA), in which we incorporated the therapeutic agent (ciprofloxacin), and to deposit this material on titanium plates using the matrix-assisted pulsed laser evaporation (MAPLE) technique. The deposited material demonstrated antibacterial properties, with all analyzed samples inhibiting the growth of tested bacterial strains, confirming the release of active substances from the investigated biocomposite. The poly(lactic-co-glycolic acid)-ciprofloxacin (PLGA-CIP) nanoparticle scaffolds displayed a prolonged local sustained release profile over a period of 45 days, which shows great promise in bone infections. Furthermore, the burst release ensures a highly efficient concentration, followed by a constant sustained release which allows the drug to remain in the implant-adjacent area for an extended time period. Full article