Search Results (73)

Multiple myeloma is a hematologic malignancy characterized by the clonal proliferation of plasma cells within the bone marrow. The tumor microenvironment plays a crucial role in multiple myeloma pathogenesis, progression, and drug resistance. Traditional two-dimensional cell culture models have been instrumental in multiple myeloma research. However, they fail to recapitulate the complex in vivo bone marrow microenvironment, leading to limited predictive value for clinical outcomes. Three-dimensional cell culture models emerged as more physiologically relevant systems, offering enhanced insights into multiple myeloma biology. Scaffold-based systems (e.g., hydrogels, collagen, and Matrigel), scaffold-free spheroids, and bioprinted models have been developed to simulate the bone marrow microenvironment, incorporating key components like mesenchymal stromal cells, osteoblasts, endothelial cells, and immune cells. These models enable the functional assessment of cell adhesion-mediated drug resistance, cytokine signaling networks, and hypoxia-induced adaptations, which are often lost in 2D cultures. Moreover, 3D platforms demonstrated improved predictive value in preclinical drug screening, facilitating the evaluation of novel agents and combination therapies in a setting that better mimics the in vivo tumor context. Hence, 3D cultures represent a pivotal step toward bridging the gap between basic myeloma research and translational applications, supporting the development of more effective and patient-specific therapies. Full article

This work evaluates the effectiveness of in situ and ex situ passivation methods for mitigating the pyrophoricity of uranium–6 wt.% niobium spherical powders produced via the hydride–dehydride process coupled with plasma spheroidization. Oxide layer thickness was characterized using STEM/EDX, and pyrophoricity was assessed by a UN-recommended test method, which involves directly dropping the powders in the air. In situ passivation, performed by introducing flowing oxygen during spheroidization, produced oxide layers ranging from tens to hundreds of nanometers but resulted in inconsistent pyrophoricity mitigation at lower oxygen flow rates. Ex situ passivation, achieved by slow oxygen exposure over several months, formed uniform oxide layers of approximately 20 nm and consistently mitigated pyrophoricity. Despite requiring higher bulk oxygen content, in situ passivation enables faster processing and control of oxygen, while ex situ passivation achieves superior oxide uniformity with lower oxygen incorporation. These findings highlight the trade-offs between passivation methods and provide a foundation for improving the safety and scalability of reactive metal powder production. Full article

This work presents a new approach for the fabrication of 316L/Al₂O₃ composites, based on a combination of spray granulation, radio frequency (RF) plasma spheroidization and spark plasma sintering (SPS). Initially, a suspension containing 316L and alumina powders is formulated by precisely adjusting the pH and selecting an appropriate dispersant, thereby ensuring homogeneous dispersion of the constituents. The spray granulation process then produces granules with controlled size and morphology. RF plasma spheroidization, carried out using a TekSphero-40 system, is investigated by varying parameters such as the power, gas flow rates, injection position and feed rate, in order to optimize the formation of spherical and dense particles. The analysis reveals a marked sensitivity to heat transfer from the plasma to the particles, with a tendency for fine particles to segregate, which underscores the necessity for precise control of the processing conditions. Finally, SPS densification, performed under a constant pressure and a rigorously controlled thermal cycle, yields composites with excellent density and hardness characteristics. This study thus demonstrates that the proposed hybrid process offers an optimal synergy between a uniform distribution of alumina and a controlled microstructure, opening up promising avenues for the design of high-performance composite materials for demanding applications. Full article

Standard 2D cultures inadequately mimic the natural microenvironment of mesenchymal stromal cells (MSCs), compromising their properties. This study investigated the impact of 3D cultures in spheroids, alginate microspheres (AMSs), and blood plasma scaffolds on human-adipose-derived MSC behavior. The cell morphology, viability/apoptosis (6-CFDA/Annexin-Cy3.18), actin filament development (phalloidin-FITC), and metabolic activity (Alamar Blue) were assessed on the 3rd day of the generated 3D construct cultures. The abilities for adipogenic and osteogenic differentiation were evaluated after 21 days of culture in media with inducers by Nile Red and Alizarin Red staining, respectively. The 3D culture supported closer-to-physiological cell interactions and morphology and resulted in F-actin reduction compared with the 2D culture. While the metabolic activity was elevated in the scaffolds, it was significantly reduced in the spheroids and AMSs, which reflected natural-like quiescence. The differentiation was maintained across all the 3D constructs. These findings highlight the essential influence of 3D construct design on MSC function, underscoring its potential for advancing both in vitro models and cell-based therapies. Full article

Background/Objectives: Cold atmospheric plasma (CAP) has shown a strong anticancer effect on a variety of tumors, presenting a new approach for the effective treatment of oral squamous cell carcinoma (OSCC), one of the most prevalent malignant neoplasms with a high mortality rate. Here, we aimed to comprehensively investigate the antitumor potential of two approaches of CAP treatment on both two-dimensional and three-dimensional OSCC cell line models, as well as to analyze whether plasma treatment enhances the sensitivity of OSCC to chemotherapy. Methods: An in-house designed plasma needle, with helium as a working gas, was used to treat the SCC-25 cell line directly or indirectly via plasma-treated medium (PTM). The antitumor effect of CAP was assessed by measuring cell viability, apoptosis, adhesion, and migration. In addition, the combined effect of PTM and cisplatin was analyzed in SCC-25 tumor spheroids, as a more complex and reliable in vitro model. Results: Both plasma treatments showed time-dependent antitumor effects affecting their viability, adhesion, and migration. The rate of apoptosis was higher after incubation with PTM and is mediated by the intrinsic pathway. By utilizing the 3D spheroid carcinoma model, we confirmed the antitumor potential of CAP and additionally demonstrated an increased chemosensitivity of PTM-treated carcinoma cells. Conclusions: The results of our study illustrate a promising avenue for the application of CAP as a therapeutic option for OSCC, either as a standalone treatment or in combination with cisplatin. Full article

Melanoma is an aggressive disease that arises from mutations in the cells that produce the pigment melanin, melanocytes. Melanoma is characterized by a high mortality rate, due to avoidance of applied therapies and metastasis to other organs. The peculiar features of boron neutron capture therapy (BNCT), particularly its cell-level selectivity, make BNCT a promising modality for melanoma treatment. However, appropriate cellular models should be used to study new therapies or improve the efficacy of existing therapies. Spheroids, which have been used for years for in vitro studies of the efficacy of anti-cancer therapies, have many characteristics shared with tumors through which they can increase the accuracy of the cellular response compared to 2D culture in vitro studies and reduce the use of animals for research in the future. To the best of our knowledge, when we started researching the use of spheroids in BNCT in vitro, there was no publication showing such use. Our study aimed to evaluate the efficacy of a 3D cellular model (spheroids) for testing BNCT on melanoma cells. We assessed boronophenylalanine (¹⁰BPA) uptake using inductively coupled plasma mass spectrometry in both spheroids and 2D cultures of melanoma and melanocytes. DNA damage, Ki67 protein expression, and spheroid growth were analyzed. The experimental groups included: (1) IR_B (neutron flux + 50 µg ¹⁰B/mL), (2) IR (neutron flux alone), (3) C_B (no irradiation, 50 µg ¹⁰B/mL), and (4) C (no irradiation and no treatment with boron). The total absorbed doses were estimated to be 2.1–3.1 Gy for IR_B cells and spheroids as well as 8.3–9.4 Gy for IR_B spheroids, while estimated doses for IR cells were 0.5–1.9 Gy. The results indicated that IR_B spheroids might exhibit a reduced diameter. Melanoma cells in the 3D model showed that their DNA damage levels may be higher than those in the 2D model. Moreover, the Ki67 assay revealed differences in the expression of this marker between irradiated melanoma cell lines. In conclusion, preincubation with ¹⁰BPA enhances BNCT efficacy, leading to cell growth inhibition and increased DNA fragmentation. Differences in DNA damage between 2D and 3D models may be due to dissimilarities in cell metabolism caused by a changed cell architecture. Full article

Alumina is the most widely used oxide ceramic, and its applications are widespread in engineering and in biomedical fields. Its spheroidization was performed by a prototypal direct current (DC) thermal plasma, which was designed and installed at ENEA, investigating surface morphology, particle size distribution, crystallinity, spheroidization, and reactivity. Features such as morphology and porosity significantly influence the flowability of the powder on the printer bed and, consequently, the density of the printed parts. It has been reported that spherical powder shape is highly recommended in additive manufacturing (AM) due to its superior flowability compared to other shapes whose interaction between powder particles results in poor flowability. In this paper, the spheroidization process of alumina powders using two different DC plasma powers and two kinds of secondary gas is reported. The average value of the circularity of the powders, after plasma treatment, has always been greater than or equal to 0.8 with the degree of the spheroidization over 90% at high power. The best process parameters of the thermal plasma were properly selected to produce spherical powders suitable for AM applications, and powders with high circularity were successfully obtained. Forming, debinding, and sintering tests were performed to verify the processability and the densification of produced powders, with good results in terms of density (97%). Full article

Lung cancer is the most common type of malignant tumor worldwide. Plasma-activated medium (PAM) is an innovative cancer treatment method that has received considerable scientific attention. The objective of this study is to evaluate the effects of PAM on the anti-tumor characteristics of non-small cell lung cancer (NSCLC) cells in two-dimensional (2D) and three-dimensional (3D) cultures. The effects of PAM treatment on the proliferative and migratory capabilities of A549 cells in 2D and 3D cultures were assessed using MTT, migration, invasion assays, and cell cycle, respectively. The study also investigated the impact of PAM treatment on the changes in the content of intracellular and extracellular reactive species and analyzed protein expression using the Western Blot method. PAM treatment inhibited the viability, migration, and invasion abilities of A549 cells in both 2D and 3D cultures, suppressed the epithelial–mesenchymal transition (EMT) process, and downregulated the expression of the RAS/ERK signaling pathway, which effectively inhibited tumor spheroid formation. Additionally, the effect of PAM on A549 cells was mediated through ROS-induced oxidative reactions, and PAM treatment exhibited greater cytotoxicity in 2D culture compared to 3D culture. As compared to 2D, the 3D cell culture model provides a viable in vitro cell model for studying the mechanisms of PAM treatment in lung cancer. PAM represents an effective new treatment for NSCLC. Full article

Additive manufacturing is a promising and actively developing method for the synthesis of metal products. The development of techniques for the production of spherical powder particles with specified properties from metals and alloys represents a significant challenge in the field of additive manufacturing. A new method for the production of titanium powders with spherical particles has been proposed, including the method of hydrogenation and dehydrogenation with subsequent spheroidization in thermal plasma. Titanium sponge, used as a feedstock, was saturated with hydrogen using the energy-efficient self-propagating high-temperature synthesis (SHS) method. The resulting hydride was then mechanically ground and then dehydrogenated by thermal decomposition in a vacuum furnace. The resulting precursor was subjected to plasma treatment, which resulted in a product (titanium powder) with a high degree of spheroidization. The physical, chemical, and technological parameters of the titanium powders were investigated. It was found that the final product, spherical titanium powder, has the necessary properties for use in additive manufacturing technologies. Full article

The process of obtaining powders from the 5–50 μm fraction of a W-Ni-Fe system consisting of particles with predominantly spherical shapes was investigated. Experimental studies on the plasma–chemical synthesis of a nanopowder composed of WNiFe-90 were carried out in a plasma reactor with a confined jet flow. A mixture of tungsten trioxide, nickel oxide, and iron oxide powders interacted with a flow of hydrogen-containing plasma generated in an electric-arc plasma torch. The parameters of the spray-drying process and the composition of a suspension consisting of WNiFe-90 nanoparticles were determined, which provided mechanically strong nanopowder microgranules with a rounded shape and a homogeneous internal structure that contained no cavities. The yield of the granule fraction under 50 μm was 60%. The influence of the process parameters of the plasma treatment of the nanopowder microgranules in the thermal plasma flow on the degree of spheroidization and the microstructure of the obtained particles, seen as their bulk density and fluidity, was established. It was shown that the plasma spheroidization of the microgranules of the W-Ni-Fe system promoted the formation of a submicron internal structure in the obtained spherical particles, which were characterized by an average tungsten grain size of 0.7 μm. Full article

This review explores the critical role of powder quality in metal 3D printing and the importance of effective powder recycling strategies. It covers various metal 3D printing technologies, in particular Selective Laser Melting, Electron Beam Melting, Direct Energy Deposition, and Binder Jetting, and analyzes the impact of powder characteristics on the final part properties. This review highlights key challenges associated with powder recycling, including maintaining consistent particle size and shape, managing contamination, and mitigating degradation effects from repeated use, such as wear, fragmentation, and oxidation. Furthermore, it explores various recycling techniques, such as sieving, blending, plasma spheroidization, and powder conditioning, emphasizing their role in restoring powder quality and enabling reuse. Full article

Extracellular HSP90α (eHSP90α) is a promoter of tumor development and malignant progression. Patients with malignancies, including pancreatic ductal adenocarcinoma (PDAC), have generally shown 5~10-fold increases in serum/plasma eHSP90α levels. In this study, we developed a humanized antibody HH01 to target eHSP90α and evaluated its anticancer efficacy. HH01, with novel complementarity-determining regions, exhibits high binding affinity toward HSP90α. It recognizes HSP90α epitope sites ₂₃₅AEEKEDKEEE₂₄₄ and ₂₅₁ESEDKPEIED₂₆₀, with critical amino acid residues E237, E239, D240, K241, E253, and K255. HH01 effectively suppressed eHSP90α-induced invasive and spheroid-forming activities of colorectal cancer and PDAC cell lines by blocking eHSP90α’s ligation with the cell-surface receptor CD91. In mouse models, HH01 potently inhibited the tumor growth of PDAC cell grafts/xenografts promoted by endothelial-mesenchymal transition-derived cancer-associated fibroblasts while also reducing serum eHSP90α levels, reflecting its anticancer efficacy. HH01 also modulated tumor immunity by reducing M2 macrophages and reinvigorating immune T-cells. Additionally, HH01 showed low aggregation propensity, high water solubility, and a half-life time of >18 days in mouse blood. It was not cytotoxic to retinal pigmented epithelial cells and showed no obvious toxicity in mouse organs. Our data suggest that targeting eHSP90α with HH01 antibody can be a promising novel strategy for PDAC therapy. Full article

The tumor suppressor gene F-box and WD repeat domain-containing (FBXW) 7 reduces cancer stemness properties by promoting the protein degradation of pluripotent stem cell markers. We recently demonstrated the transcriptional repression of FBXW7 by the three-dimensional (3D) spheroid formation of several cancer cells. In the present study, we found that the transcriptional activity of FBXW7 was promoted by the inhibition of the Ca²⁺-activated K⁺ channel, K_Ca1.1, in a 3D spheroid model of human prostate cancer LNCaP cells through the Akt-Nrf2 signaling pathway. The transcriptional activity of FBXW7 was reduced by the siRNA-mediated inhibition of the CCAAT-enhancer-binding protein C/EBP δ (CEBPD) after the transfection of miR223 mimics in the LNCaP spheroid model, suggesting the transcriptional regulation of FBXW7 through the Akt-Nrf2-CEBPD-miR223 transcriptional axis in the LNCaP spheroid model. Furthermore, the K_Ca1.1 inhibition-induced activation of FBXW7 reduced (1) K_Ca1.1 activity and protein levels in the plasma membrane and (2) the protein level of the cancer stem cell (CSC) markers, c-Myc, which is a molecule degraded by FBXW7, in the LNCaP spheroid model, indicating that K_Ca1.1 inhibition-induced FBXW7 activation suppressed CSC conversion in K_Ca1.1-positive cancer cells. Full article

To modify the structure of thermal barrier coatings and improve their high-temperature resistance, induction plasma spheroidization (IPS) technology was applied to regulate the structure of YSZ powders in this study. The surface morphology, particle size distribution, phase composition, and internal microstructure of the conventional agglomerated and spheroidized powders were characterized using scanning electron microscopy and focused ion beam analysis methods. The results showed that the microstructure of the powders presented uneven evolution in the induction plasma stream. Due to the existence of the temperature gradient along the radial direction of the powders, the IPS powders consisted of outer dense shells and internal porous cores. The mechanical property of such shell–core structure was analyzed by using the finite elemental simulation method. In addition, coatings were prepared using the IPS powders and the agglomerated powders. The IPS coating showed improved water-cooling thermal cycling resistance compared to the conventional coating. Full article

In this study, the induction plasma spheroidization (IPS) technique was adopted to improve the microstructure and properties of the traditional agglomerated ZrO₂-7wt%Y₂O₃ (YSZ) powders used in thermal barrier coating (TBC) applications. Compared with agglomerated YSZ powders, IPS-treated powder has a more desirable microstructure, and the overall performance of the spray powders for TBC preparation is significantly improved. Specifically, IPS-treated powder has a dense, solid, defect-free, and chemically uniform microstructure, and its apparent density, flowability, and powder strength are significantly improved, which is believed to substantially enhance the coating performance when prepared with this IPS-treated powder. Full article