Matrix Mineralization Research Articles

Improvement of osteogenic differentiation potential of placenta-derived mesenchymal stem cells by metformin via AMPK pathway activation.

Placenta-derived human mesenchymal stem cells (PL-MSCs) have gained a lot of attention in the field of regenerative medicine due to their availability and bone-forming capacity. However, the osteogenic differentiation capacity of these cells remains inconsistent and could be improved to achieve greater efficiency. Although metformin, a widely used oral hypoglycemic agent, has been shown to increase bone formation in various cell types, its effect on osteogenic differentiation of PL-MSCs has not yet been investigated. Therefore, the objective of this study was to examine the effect of metformin on the osteogenic differentiation capacity of PL-MSCs and the underlying mechanisms. The PL-MSCs were treated with 0.5 to 640µM metformin and their osteogenic differentiation capacity was examined by an alkaline phosphatase (ALP) activity assay, Alizarin red S staining and expression levels of osteogenic genes. The role of adenosine 5'-monophosphate-activated protein kinase (AMPK) signaling in mediating the effect of metformin on the osteogenic differentiation capacity of PL-MSCs was also investigated by determining levels of phosphorylated AMPK(pAMPK)/AMPK ratio and by using compound C, an AMPK inhibitor. The results showed that 10-160µM metformin significantly increased the viability of PL-MSCs in a dose- and time-dependent manner. Furthermore, 80-320µM metformin also increased ALP activity, matrix mineralization, and expression levels of osteogenic genes, runt-related transcription factor 2 (RUNX2), osterix (OSX), osteocalcin (OCN) and collagen I (COL1), in PL-MSCs. Metformin increases osteogenic differentiation of PL-MSCs, at least in part, through the AMPK signaling pathway, since the administration of compound C inhibited its enhancing effects on ALP activity, matrix mineralization, and osteogenic gene expression of PL-MSCs. This study demonstrated that metformin at concentrations of 80-320μM significantly enhanced osteogenic differentiation of PL-MSCs in a dose- and time-dependent manner, primarily through activation of the AMPK signaling pathway. This finding suggests that metformin could be used with other conventional drugs to induce bone regeneration in various bone diseases. Additionally, this study provides valuable insights for future osteoporosis treatment by highlighting the potential of modulating the AMPK pathway to improve bone regeneration.

LSD1 Conditional Myeloid Cell Knockout Mice have Decreased Osteoclast Differentiation Due to Increased IFN-β Gene Expression

Abstract Osteoclasts are large multinucleated cells that degrade bone mineral and extracellular matrix. Investigating the epigenetic mechanisms orchestrating osteoclast differentiation is key to our understanding of the pathogenesis of skeletal related diseases such as periodontitis and osteoporosis. Lysine specific demethylase 1 (LSD1/KDM1A) is a member of the histone demethylase family that mediates the removal of mono- and dimethyl groups from H3K4 and H3K9 to elicit dichotomous effects on gene expression. Prior to our study, little was known about the contributions of LSD1 to skeletal development and osteoclast differentiation. Here we show that conditional deletion of Lsd1 within the myeloid lineage or macrophage/osteoclast precursors results in enhanced bone mass of male and female mice accompanied by diminished osteoclast size in vivo. Furthermore, Lsd1 deletion decreased osteoclast differentiation and activity within in vitro assays. Our bulk RNA-SEQ data suggests Lsd1 ablation in male and female mice inhibits osteoclast differentiation due to enhanced expression of IFN-β target genes. Lastly, we demonstrate that LSD1 forms an immune complex with HDAC1 and HDAC2. These data suggest that the combination of methylation and acetylation of histone residues, facilitated by LSD1, mechanistically promotes osteoclast gene expression.

Dental Pulp Stem Cell Conditioned Medium Enhance Osteoblastic Differentiation and Bone Regeneration.

Cell-free approaches, utilizing mesenchymal stem cell secretome, have promising prospects in various fields of regenerative medicine. In this study, we examined in vitro and in vivo the potential of dental pulp stem cell-conditioned medium (DPSC-CM) for bone regeneration. The secretome of undifferentiated stem cells from dental pulp were collected, and the effects of this DPSC-CM were assessed for osteodifferentiation of osteoblast-like cells (MG-63) and osteoblasts deriving from DPSC. Cell proliferation, alkaline phosphatase (ALP) activity, gene expression of Runt-related transcription factor 2 (Runx2), Bone Sialoprotein (BSP), Osteocalcin (OCN), and extracellular matrix mineralization were evaluated. The rat caudal vertebrae critical size defect model was to investigate the effect of DPSC-CM in vivo. Results showed that DPSC-CM induced cell growth, and increased ALP activity and the expression of key marker genes at an early stage of osteoblastic differentiation compared to control. A rat bone defect model was used to illustrate the effect of DPSC-CM in vivo. The bone density within the defects were improved using conditioned medium, even though there was no significant difference between the control and DPSC-CM groups. The analysis of DPSC-CM by human growth factor antibody array revealed the presence of several factors involved in osteogenesis. Taken together, these findings indicate that DPSC-CM is a promising therapeutic candidate for bone regenerative therapy, accelerating the maturation of osteoblastic cells. And even though safety and efficiency of DPSC-CM have to be confirmed in preclinical studies, these results represent a first step toward clinical application.

Enhanced ICP-MS detection of 24 elemental impurities in complex, high matrix mineral, medicinal lanthanum carbonates according to ICH Q2 (R2).

Validation of the specificity of ICP-MS methods by ICH Q2 (R2) through spiking experiments cannot characterize the multi-atomic interference of complex high matrix samples, possibly affecting the accuracy of the method and reliability of results. In this study, we highlight this issue by investigating the elemental impurities in lanthanum carbonate raw materials and use isotope ratio analysis to overcome this limitation and establishing an accurate ICP-MS method for 24 elemental impurities (listed in ICH Q3D). An Agilent 7900 ICP-MS was used with an automatic sampler for sample determination in the He mode. The isotope ratio of elemental impurities in the spiked samples was analyzed to characterize polyatomic interference and select the exclusive mass number of elemental impurities. While the recovery rate of most elemental impurities met the requirements, that of selenium (default measurement mass number 78Se) exceeded the standard in the matric sample. The isotope ratio of Se (78Se/82Se) was much higher than the theoretical value, indicating that the response intensity of m/z 78 was formed by the combination of 78Se and other mass-to-charge ratios, such as LaOH2+ formed by the large amount of La in the matrix. Therefore, 82 was chosen as the mass number for Se. The validation results indicate that the method has strong specificity, high accuracy, and is simple and facile. This study provides technical support for the control of elemental impurities in lanthanum carbonates and isotope ratios can be used as a supplementary means of spiked recovery rates.

Investigating the potential effect of Holothuria scabra extract on osteogenic differentiation in preosteoblast MC3T3-E1 cells

The present medical treatments of osteoporosis come with adverse effects. It leads to the exploration of natural products as safer alternative medical prevention and treatment. The sea cucumber, Holothuria scabra, has commercial significance in Asian countries with rising awareness of its properties as a functional food. This study aims to investigate the effects of the inner wall (IW) extract isolated from H. scabra on extracellular matrix maturation, mineralization, and osteogenic signaling pathways on MC3T3-E1 preosteoblasts. The IW showed the expression of several growth factors. Molecular docking revealed that H. scabra BMP2/4 binds specifically to mammal BMP2 type I receptor (BMPR-IA). After osteogenic induction, the viability of cells treated with IW extract was assessed and designated with treatment of 0.1, 0.5, 1, and 5 µg/ml of IW extract for 21 consecutive days. On days 14 and 21, treatments with IW extract at 1 and 5 µg/ml showed increased alkaline phosphatase (ALP) activity and calcium deposit levels in a dose-dependent manner compared to the control group. Moreover, the transcriptomic analysis of total RNA of cells treated with 5 µg/ml of IW extract exhibited upregulation of TGF-β, PI3K/Akt, MAPK, Wnt and PTH signaling pathways at days 14. This study suggests that IW extract from H. scabra exhibits the potential to enhance osteogenic differentiation and mineralization of MC3T3-E1 preosteoblasts through TGF-β, PI3K/Akt, MAPK, Wnt and PTH signaling pathways. Further investigation into the molecular mechanisms underlying the effect of IW extract on osteogenesis is crucial to support its application as a naturally derived supplement for prevention or treatment of osteoporosis.

Simulated microgravity environment inhibits matrix mineralization during the osteoblast to osteocyte differentiation

This study investigates the effects of microgravity on the differentiation and mineralization of IDG-SW3 osteocyte-like cells to understand the response of bone cells to microgravity and develop strategies to mitigate bone loss in astronauts. IDG-SW3 cells were cultured in collagen-coated dishes and subjected to a 3D clinostat to simulate microgravity 14 days after initiating differentiation. The static group remained under normal gravity. Cells were analyzed on days 14, 18, 22, and 26. Alizarin red staining demonstrated a substantial and time-dependent increase in mineralization in the static group, whereas the microgravity group exhibited little detectable mineralization throughout the experimental period. Quantitative RT-PCR revealed significant upregulation of Rankl, Alpl, Dmp1, and Fgf23 and downregulation of Sost and Phex in the microgravity group. RNA sequencing on day 26 showed distinct gene expression profiles between conditions. Heatmaps highlighted upregulated genes (Ptgs2, Alpl, Comp, Atf4, Lox) and downregulated genes (Rspo2, Ank, Ptn, Mmp13, Aspn, Spp1) under microgravity. Gene ontology (GO) enrichment analysis indicated that upregulated genes were associated with cytoskeletal organization and receptor activities, while downregulated genes were linked to extracellular matrix components and immune response. These findings provide insights into the molecular mechanisms of bone loss in space and emphasize the importance of gravity in bone remodeling. Future studies should validate these genes' functions in osteocyte biology under microgravity.

Endochondral ossification: insights into the cartilage mineralization processes achieved by an anhydrous freeze substitution protocol

Growth plate cartilage (GP) serves as a dynamic site of active mineralization and offers a unique opportunity to investigate the cell-regulated matrix mineralization process. Transmission electron microscopy (TEM) provides a means for the direct observation of these mechanisms, offering the necessary resolution and chemical analysis capabilities. However, as mineral crystallinity is prone to artifacts using aqueous fixation protocols, sample preparation techniques are critical to preserve the mineralized tissue in its native form. We optimized cryofixation by high-pressure freezing followed by freeze substitution in anhydrous acetone containing 0.5% uranyl acetate to prepare murine GP for TEM analysis. This sample preparation workflow maintains cellular and extracellular protein structural integrity with sufficient contrast for observation and without compromising mineral crystallinity. By employing appropriate sample preparation techniques, we were able to observe two parallel mineralization processes driven by chondrocytes: 1) intracellular- and 2) extracellular-originating mineralized vesicles. Both mechanisms are based on sequestering calcium phosphate (CaP) within a membrane-limited structure, albeit originating from different compartments of the chondrocytes. In the intracellular originating pathway, CaP accumulates within mitochondria as globular CaP granules, which are incorporated into intracellular vesicles (500-1000 nm) and transported as granules to the extracellular matrix (ECM). In contrast, membrane budding vesicles with a size of approximately 100-200nm, filled with needle-shaped minerals were observed only in the ECM. Both processes transport CaP to the collagenous matrix via vesicles, they can be differentiated based on the vesicle size and mineral morphologies. Their individual importance to the cartilage mineralization process is yet to be determined. Statement of SignificanceWe do not fully understand the process by which epiphyseal cartilage mineralizes - a vital step in endochondral bone formation. Previous work has proposed that mitochondria and intracellular vesicles are storage sites for the delivery of mineral to collagen fibrils. However, these concepts are founded on results from in vitro models of mineralization; no prior work has observed mineral-containing intracellular vesicles or mitochondria in developing epiphyseal cartilage. Here we developed a new cryofixation preparation route for transmission electron microscopy (TEM) imaging that has disclosed a cell-regulated process of mineralization in epiphyseal cartilage. High resolution TEM images revealed an involvement of mitochondria and intracellular and extracellular vesicles in delivering transient mineral phases to the collagen fibrils to promote cartilage mineralization.

Matrix Gla protein suppresses osteoblast senescence and promotes osteogenic differentiation by the PI3K-AKT signaling pathway

Age-related bone loss in mice is associated with senescent cell accumulation and reduced bone formation by osteoblasts. Matrix Gla protein (MGP), secreted by osteoblasts, is pivotal in regulating the bone extracellular matrix mineralization. Previous research has demonstrated that Mgp null mice exhibit osteopenia and fractures, and ultimately die prematurely. To elucidate the mechanisms underlying MGP’s role of MGP in bone metabolism, we generated osteoblast-specific Mgp knockout (Mgp cKO) mice by crossing Mgpfl/fl mice with Bglap-Cre mice. The study revealed that in 3-month-old Mgp cKO male mice, trabecular bone volume decreased, and the senescence marker protein p21 increased. Primary osteoblasts from Mgp cKO mice exhibited markers of DNA damage and senescence, such as increased γH2AX foci, p21, and senescence-associated β-galactosidase staining, as well as attenuated cellular proliferation and osteogenic differentiation abilities. In addition, bone marrow stromal cells’ colony formation and spontaneous osteogenic ability were impaired in Mgp cKO mice, whereas osteoclastogenesis was enhanced. In vitro treatment with recombinant human MGP promotes osteogenesis in osteoblasts derived from Mgp cKO mice via the PI3K-AKT signaling pathway. Thus, our results suggest that MGP is protective by suppressing osteoblast senescence, offering new insights into potential therapeutic strategies for age-related osteoporosis.

Consideration of spectral interference in total reflection X-ray fluorescence analysis using a limited number of calibration samples: Case study of ocean polymetallic nodules

A novel approach for quantitative analysis in total-reflection X-ray fluorescence (TXRF) which can be employed for the samples with complex matrices inducing overlapping spectral signals in the scenario of limited availability of standard samples is proposed. The approach is based on the least squares (LS) decomposition of real spectra into the weighted sum of simulated individual element subspectra and requires only a single sample of matrix-matched reference material. Oceanic polymetallic nodules and crusts, having complex mineral matrix and containing high concentrations of overlapping elements, were chosen to demonstrate the feasibility of the approach in quantification of 11 elements. The comparison of the results obtained with LS decomposition, internal standard and linear calibration with three standard samples was performed. It was demonstrated that the performance of the proposed approach and of the linear calibration was better than that of internal standard for most of the elements; however, the proposed method requires only a single standard sample.

Innovative 3D-Printed Titanium Specimens Favor a Modulation of Inflammation in Dental Pulp Stem Cells During Liposome-Triggered Mineralization.

developing customized titanium specimens, with innovative surfaces, is a suitable strategy to overcome implant failure. Additionally, a faster and efficient osteogenic commitment assists tissue regeneration. To investigate the interplay between inflammation and differentiation upon implantation, Dental Pulp Stem Cells (DPSCs) were cultured on 3D-printed titanium owning an internal open cell form, administering osteogenic factors by a liposomal formulation (LipoMix) compared to traditional delivery of differentiation medium (DM). osteogenic differentiation was evaluated by western blot, by measuring β1 integrin expression, and by and real-time RT-PCR, by measuring SP7 and Collagen I gene expression; while.angiogenesis was characterized by measuring VEGF secretion levels. Matrix mineralization was assessed by means of Alizarin Red Staining, cell adhesion and inflammation responses through western blot, enzymatic and ELISA assays evaluating Nrf2 expression, catalase activity and Prostaglandin E2 secretion, respectively. LipoMix enhances cell proliferation and adhesion, as revealed by increased integrin β1 expression. Mineralized matrix deposition, SP7 gene expression, Collagen I release and Alkaline Phosphatase activity appear increased in LipoMix condition. Additionally, the redox-sensitive transcription factor Nrf2 is overexpressed at the earliest experimental times, triggering the catalase activity. data reported confirm that internal topography and post-production treatments on titanium surfaces dynamically and positively condition the DPSC progress towards the osteogenic phenotype, moreover, the combination with LipoMix fastens the positive modulation of inflammation under osteogenic conditions. Therefore, the development of customized surfaces along with the administration of differentiating factors enclosed in a liposomal delivery system, could represent a promising and innovative tool in regenerative dentistry.

Potential of Cranberry to Stimulate Osteogenesis: An In Vitro Study

This study investigated the potential of Cranberry extract to stimulate osteogenesis in vitro. The total phenolic and monomeric anthocyanin contents in the Cranberry were determined. Liquid chromatography coupled with mass spectrometry was used to identify the Cranberry’s constituents. To assess the Cranberry’s cytotoxicity, a thiazolyl blue tetrazolium bromide assay was employed. Concerning the osteogenesis potential of Cranberry, alkaline phosphatase (ALP) activity, bone morphogenetic protein 2 (BMP-2) expression, and extracellular matrix mineralization were evaluated. The total phenolic content was 522.72 ± 9.80 mg GAE g-1 ES and 364.95 ± 12.49 mg GAE/g detected by the Fast Blue BB and Folin–Ciocalteu method, respectively. For monomeric anthocyanin, the content was 460 ± 30 mg ECG g-1 ES. Moreover, Cranberry concentrations ranged from 62.5 to 500 mg/mL and were found to be biocompatible with osteoblasts and mesenchymal stromal cells. Regarding osteogenesis, 20 mg/mL of Cranberry promoted 2-fold more ALP activity and almost 1.5-fold more BMP-2 than compared to the positive control group. Additionally, 200 mg/mL of Cranberry stimulated a 1.7-fold increase in extracellular matrix mineralization compared to the positive control group. In conclusion, Cranberry displayed potential in stimulating early and late markers of osteogenesis. Its ability to promote osteogenesis and its biocompatibility at higher concentrations hold promise for future application into biomaterials for bone regeneration.

Bioleaching of Industrial Metallic Steel Waste by Mixed Cultures of Thermoacidophilic Archaea

Different mixed cultures of extremely thermoacidophilic microorganisms were used for bioleaching of metalliferous industrial dust waste derived from the basic oxygen furnace (BOF) steelmaking process. Such mixed cultures can extract various metals from multi-metallic BOF-dust waste, improving the metal dissolution and bioleaching performance in frames of metal recycling processes to assist circular economies and waste management. The results of the investigation showed that mixed cultures of thermoacidophilic archaea of the order Sulfolobales (Acidianus spp., Sulfolobus spp., and Metallosphaera sedula) during their growth in laboratory glass bioreactors provided a superior bioleaching system to Acidianus manzaensis alone. Depending on the composition of mixed thermoacidophilic cultures, extraction of various metals from BOF-dust could be achieved. Among the three different types of mixed cultures tested, the mixed culture system of A. manzaensis, A. brierleyi, and S. acidocaldarius was most effective for extraction of major elements (Fe, Ca, Zn, Mn, and Al). The mixed culture of A. manzaensis, A. brierleyi, and M. sedula showed high performance for bioleaching of most of the minor elements (Cu, Ni, Pb, Co, Mo, and Sr). The efficient ability of mixed cultures to colonise the mineral matrix of the metal waste product was observed via scanning electron microscopy, while their metal extraction capacities were analysed by inductively coupled plasma mass spectrometry. These investigations will promote the further design of microbial consortia in order to break down the solid matrix and efficiently extract metals from metalliferous waste materials.

Mitigation of Fluoride Contamination in Drinking Water Supply Sources by Adsorption Using Bone Char: Effects of Mineral and Organic Matrix

This study focused on fluoride (F−) contamination of water sources in Bahimi village, Cameroon. After the first investigation, results revealed that all water samples collected had elevated concentrations of fluoride ions (2.3 ± 0.1) mg/L to (4.5 ± 0.2) mg/L above the WHO guidelines (less than 1.5 mg/L). To mitigate the F− levels, the use of bone char (BC) as an adsorbent material was proposed and its performance was tested. BC was prepared from bovine bones at different calcination temperatures (350 °C, 450 °C, 550 °C and 650 °C) and residence times (1 h and 2 h). The prepared materials were characterized in detail by SEM/EDS, BET, FTIR, and XRD. The BET findings indicated that the surface area of BC samples decreased with increasing calcination temperature and residence time. At a lower heating temperature and holding time (350 °C, 1 h), the prepared BC exhibited a higher specific surface area (112.3 ± 0.3) m2/g and adsorption capacity for F− in the sampled water. Also, the batch adsorption experiments showed that the optimized adsorbent dose of 8 g/L facilitates the reduction in the F− level of the sampled water below the acceptable limit level (1.5 mg/L) within 5 min of treatment. The presence of Ca2+ and Mg2+ in natural water has a positive effect on the removal of F− in BC resulting in a high adsorption performance range of (72.5 ± 1.4)% to (80.3 ± 0.6)%. It was found that the adsorption of Ca2+ on the BC surface occurs via cation exchange with Na+. However, an increase in dissolved organic carbon (DOC) in the treated water limited the application of BC. Overall, the study presented a cost-effective adsorbent for the removal of this recalcitrant ion in the water source.

TMEM175 plays a crucial role in osteoblast differentiation by regulating lysosomal function and autophagy

Bone provides structural support, enables movement, protects internal organs, regulates calcium and phosphorus levels, and contains bone marrow essential for hematopoiesis. Osteoblasts are specialized cells responsible for bone formation through the secretion of extracellular matrix components. Transmembrane protein 175 (TMEM175), which functions as an endosomal/lysosomal K+ channel and a lysosomal H+ channel, regulates lysosomal function and autophagy. Despite the recognized importance of lysosomes and autophagy in osteoblast differentiation, the specific role of TMEM175 in osteoblast differentiation has not been revealed. In this study, we investigated whether TMEM175 is associated with human bone mineral densityand fracture and examined the role of TMEM175 in osteoblast differentiation. In analyses of single nucleotide polymorphismsof pore ion channel genes using the mouse2human database, a significant correlation between TMEM175 single nucleotide polymorphisms and human bone mineral density and fracture was identified. TMEM175 expression levels were found to increase during osteoblast differentiation from bone chip-derived mesenchymal stem cells (BMSCs). Knockdown of TMEM175 in BMSCs suppressed osteoblast differentiation, as evidenced by decreased matrix mineralization and lower expression levels of osteoblast marker genes. Further analysis indicated that TMEM175 deficiency leads to lysosomal dysfunction and partially impairs autophagic clearance during osteoblast differentiation. Moreover, the TMEM175 inhibitor 4-aminopyridinedecreased osteoblast differentiation of BMSCs. Taken together, this study reveals that TMEM175 plays an important role in osteoblast differentiation by regulating lysosomal function and autophagic clearance.

Tauroursodeoxycholic acid combined with selenium accelerates bone regeneration in ovariectomized rats.

More recently, increased studies have revealed that antioxidants can cure osteoporosis by inhibiting oxidative stress. Tauroursodeoxycholic acid (TUDCA) and Selenium (Se) have been confirmed to possess potent anti-oxidative effects and accelerate bone regeneration. In addition, very little is currently known about the effects of a combination with Se and TUDCA on bone defects in osteoporotic states. We, therefore, aimed to assess the protective effect of combination with Se and TUDCA on bone regeneration and investigate the effect and underlying mechanisms. When MC3T3-E1 was cultured in the presence of H2H2, Se, TUDCA and Se/TUDCA therapy could increase the matrix mineralization and promote expression of anti-oxidative stress markers in MC3T3-E1, while reducing intracellular reactive oxygen species (ROS) and mitochondrial ROS levels. Meanwhile, silent information regulator type 1 (SIRT1) was upregulated in response to Se, TUDCA and Se/TUDCA exposures in H2H2 treated-MC3T3-E1. In the OVX rat model, Se, TUDCA and Se/TUDCA showed a clear positive effect against impaired bone repair in osteoporosis. The results above demonstrate that Se/TUDCA exhibits superior efficacy in both cellular and animal experiments, as compared to Se and TUDCA. In conclusion, combination with Se and TUDCA stimulates bone regeneration and is a promising candidate for promoting bone repair in osteoporosis.

Extracorporeal Magnetotransduction Therapy as a New Form of Electromagnetic Wave Therapy: From Gene Upregulation to Accelerated Matrix Mineralization in Bone Healing.

Electromagnetic field therapy is gaining attention for its potential in treating bone disorders, with Extracorporeal Magnetotransduction Therapy (EMTT) emerging as an innovative approach. EMTT offers a higher oscillation frequency and magnetic field strength compared to traditional Pulsed Electromagnetic Field (PEMF) therapy, showing promise in enhancing fracture healing and non-union recovery. However, the mechanisms underlying these effects remain unclear. This study demonstrates that EMTT significantly enhances osteoblast bone formation at multiple levels, from gene expression to extracellular matrix mineralization. Key osteoblastogenesis regulators, including SP7 and RUNX2, and bone-related genes such as COL1A1, ALPL, and BGLAP, were upregulated, with expression levels surpassing those of the control group by over sevenfold (p < 0.001). Enhanced collagen synthesis and mineralization were confirmed by von Kossa and Alizarin Red staining, indicating increased calcium and phosphate deposition. Additionally, calcium imaging revealed heightened calcium influx, suggesting a cellular mechanism for EMTT's osteogenic effects. Importantly, EMTT did not compromise cell viability, as confirmed by live/dead staining and WST-1 assays. This study is the first to show that EMTT can enhance all phases of osteoblastogenesis and improve the production of critical mineralization components, offering potential clinical applications in accelerating fracture healing, treating osteonecrosis, and enhancing implant osseointegration.

Europium-Containing Nanospheres for Treating Ovariectomy-Induced Osteoporosis: Targeted Bone Remodeling and Macrophage Polarization Modulation.

Osteoporosis, characterized by reduced bone mass and structural deterioration, poses a significant healthcare challenge. Traditional treatments, while effective in reducing fracture risks, are often limited by side effects. This study introduces a novel nanocomplex, europium (Eu) ions-doped superparamagnetic iron oxide (SPIO) nanocrystals encapsulated in poly(lactic-co-glycolic acid) (PLGA) nanospheres, abbreviated as SPIO:Eu@PLGA nanospheres, as a potential therapeutic agent for osteoporosis by modulating macrophage polarization, enhancing osteoblast differentiation and inhibiting osteoclastogenesis. SPIO and SPIO:Eu nanocrystals were synthesized through pyrolysis and encapsulated in PLGA using an emulsification method. To evaluate the impact of SPIO:Eu@PLGA nanospheres on macrophage reprogramming and reactive oxygen species (ROS) production, flow cytometry analysis was conducted. Furthermore, an ovariectomized (OVX) rat model was employed to assess the therapeutic efficacy of SPIO:Eu@PLGA nanospheres in preventing the deterioration of osteoporosis. In vitro, SPIO:Eu@PLGA nanospheres significantly attenuated M1 macrophage activation induced by lipopolysaccharides, promoting a shift towards the M2 phenotype. This action is linked to the modulation of ROS and the NF-κB pathway. Unlike free Eu ions, which do not achieve similar results when not incorporated into the SPIO nanocrystals. SPIO:Eu@PLGA nanospheres enhanced osteoblast differentiation and matrix mineralization while inhibiting RANKL-induced osteoclastogenesis. In vivo studies demonstrated that SPIO:Eu@PLGA nanospheres effectively targeted trabecular bone surfaces in OVX rats under magnetic guidance, preserving their structure and repairing trabecular bone loss by modulating macrophage polarization, thus restoring bone remodeling homeostasis. The study underscores the critical role of Eu doping in boosting the anti-osteoporotic effects of SPIO:Eu@PLGA nanospheres, evident at both cellular and tissue levels in vitro and in vivo. The inclusion of Eu into SPIO matrix suggests a novel approach for developing more effective osteoporosis treatments, particularly for conditions induced by OVX. This research provides essential insights into SPIO:Eu@PLGA nanospheres as an innovative osteoporosis treatment, addressing the limitations of conventional therapies through targeted delivery and macrophage polarization modulation.

Synthesis and Characterization of Shungite Modified Poly-N-Ninylpyrrolidone-Agarose Composites for Medical Application.

A systematic investigation was conducted to synthesize hybrid composite materials that use synthetic poly-N-vinylpyrrolidone and natural (agar-agar) macromolecules with plasticizers (PEG-400) and mineral filler shungite by means of electron irradiation. The XRD and SEM data showed that the structure of the resulting hybrid composites is an interpenetrating network with distributed particles of mineral component. It has been established that the mechanical properties of hybrid composites are determined mainly by the structural organization of the interpenetrating polymer network formed under electron irradiation of the initial synthetic and natural polymer mixture in the presence of plasticizers, as well as by the conditions for intercalation of polymer segments into the mineral matrix and vice versa. It has been revealed that the degree of swelling of hybrid composites strongly depends on the concentration of a low-molecular plasticizer in the polymeric interpenetrating network, which easily impregnates into the matrix of shungite. Successfully obtained [PVP-AA-PEG] hydrogels with shungite can be applied in regenerative medicine as wound healing dressings.

Changes in Kerogen and Mineral Matrix Characteristics of Rocks of Bazhenov Deposits during Laboratory Modelling of Hydrothermal Processes

Changes in Kerogen and Mineral Matrix Characteristics of Rocks of Bazhenov Deposits during Laboratory Modelling of Hydrothermal Processes

Thermal insulation and fire protection plaster for FRP systems incorporating aerogel nanoparticles and phyllosilicates

Fiber Reinforced Polymers (FRP) Systems are the most advanced systems in structural repair and strengthening field for their minimal time of application, limited space needed, and high durability. However, FRP systems still have a major drawback that limits their utilization in many projects, namely low fire-resistance. A novel material that was introduced lately with a substantial thermal performance is Aerogel, which has been widely utilized in other fields. This study attempted to develop fire-protective plaster incorporating nano silica-aerogel particles and phyllosilicates. During the experimental process, different surfactants were assessed as wetting agents, and their impact on both cement and mineral matrices. Finally, the selected plaster was evaluated under fire conditions. The results reveal that aerogel incorporation in mineral (gypsum) matrix was successfully achieved using various types of surfactants. The mechanical and thermal performance of the developed plasters were promising, with a fire-rating performance reaching 82 minutes for FRP system.