Ultrasmall FeS2 Nanoparticles-Decorated Carbon Spheres with Laser-Mediated Ferrous Ion Release for Antibacterial Therapy.

Recent progress in nanotechnology and the ancient use of sulfur in treating dermatological disorders have promoted the development of nano-sulfides for antimicrobial applications. However, the variable valences and abundant forms of nano-sulfides have complicated investigations on their antibacterial activity. Here, carbon nanospheres (CNSs) with decoration of ultrasmall FeS2 nanoparticles (CNSs@FeS2 ) is synthesized, and their antibacterial ability and mechanism are explored. The CNSs@FeS2 released Fe2+ and sulfur ions simultaneously through dissolution and disproportionation. In vitro study indicated that the released Fe2+ killed bacteria by increasing the oxidative state of bacterial surfaces and intracellular molecules. Importantly, the released sulfur exhibited a protective effect on Fe2+ , ensuring the stable existence of Fe2+ to continuously combat bacteria. Moreover, the carbon shells of CNSs@FeS2 not only prevented the aggregation of FeS2 but also accelerated the release of Fe2+ through photothermal effects to achieve synergistic hyperthermia/Fe2+ therapy. In vivo experiments indicated that treatment with CNSs@FeS2 resulted in a marked reduction in bacterial number and improvement in survival in an acute peritonitis mouse model, and antibacterial wound experiments demonstrated high efficacy of CNSs@FeS2 -enabled synergistic hyperthermia/Fe2+ therapy. Thus, this study clarifies the antibacterial mechanism of FeS2 and offers a synergetic therapeutic platform with laser-mediated Fe2+ release for antibacterial applications.

Development and evaluation of copper-containing mesoporous bioactive glasses for bone defects therapy.

Mesoporous bioactive glasses (MBGs) are gaining increasing interest in the design of new biomaterials for bone defects treatment. An important research trend to enhance their biological behavior is the inclusion of moderate amounts of oxides with therapeutical action such as CuO. MBGs with composition (85-x)SiO2-10-CaO-5P2O5-xCuO (x = 0, 2.5 or 5 mol-%) were synthesized, investigating the influence of the CuO content and some synthesis parameters in their properties. Two series were developed; first one used HCl as catalyst and chlorides as CaO and CuO precursors, second one, used HNO3 and nitrates. MBGs of chlorides family exhibited calcium/copper phosphate nanoparticles between 10 and 20 nm in size. Nevertheless, CuO-containing MBGs of nitrates family showed metallic copper nanoparticles larger than 50 nm as well as quicker in vitro bioactive responses. Thus, MBGs of the nitrate series were coated by an apatite-like layer after 24 h soaked in simulated body fluid (SBF) a remarkably short period for a MBG containing 5% of CuO. A model, focused in the location of copper in the glass network, was proposed to relate nanostructure and in vitro behaviour. Moreover, after 24 h soaked in MEM or THB culture media, all the MBGs released therapeutic amounts of Ca2+ and Cu2+ ions. Because the quick bioactive response in SBF, the capacity to host biomolecules in their pores and to release therapeutic concentrations of Ca2+ and Cu2+ ions, MBGs of the nitrate families are proposed as excellent biomaterials for bone regeneration.

Studies on Silver Ions Releasing Processes and Mechanical Properties of Surface-Modified Titanium Alloy Implants.

Dispersed silver nanoparticles (AgNPs) on the surface of titanium alloy (Ti6Al4V) and titanium alloy modified by titania nanotube layer (Ti6Al4V/TNT) substrates were produced by the chemical vapor deposition method (CVD) using a novel precursor of the formula [Ag5(O2CC2F5)5(H2O)3]. The structure and volatile properties of this compound were determined using single crystal X-ray diffractometry, variable temperature IR spectrophotometry (VT IR), and electron inducted mass spectrometry (EI MS). The morphology and the structure of the produced Ti6Al4V/AgNPs and Ti6Al4V/TNT/AgNPs composites were characterized by scanning electron microscopy (SEM) and atomic force microscopy (AFM). Moreover, measurements of hardness, Young's modulus, adhesion, wettability, and surface free energy have been carried out. The ability to release silver ions from the surface of produced nanocomposite materials immersed in phosphate-buffered saline (PBS) solution has been estimated using inductively coupled plasma mass spectrometry (ICP-MS). The results of our studies proved the usefulness of the CVD method to enrich of the Ti6Al4V/TNT system with silver nanoparticles. Among the studied surface-modified titanium alloy implants, the better nano-mechanical properties were noticed for the Ti6Al4V/TNT/AgNPs composite in comparison to systems non-enriched by AgNPs. The location of silver nanoparticles inside of titania nanotubes caused their lowest release rate, which may indicate suitable properties on the above-mentioned type of the composite for the construction of implants with a long term antimicrobial activity.

Enhancing Wound Healing With Sprayable Hydrogel Releasing Multi Metallic Ions: Inspired by the Body's Endogenous Healing Mechanism.

In the pursuit of new wound care products, researchers are exploring methods to improve wound healing through exogenous wound healing products. However, diverging from this conventional approach, this work has developed an endogenous support system for wound healing, drawing inspiration from the body's innate healing mechanisms governed by the sequential release of metal ions by body at wound site to promote different stages of wound healing. This work engineers a multi-ion-releasing sprayable hydrogel system, to mimic this intricate process, representing the next evolutionary step in wound care products. It comprises Alginate (Alg) and Fibrin (Fib) hydrogel infused with Polylactic acid (PLA) polymeric microcarriers encapsulating multi (calcium, copper, and zinc) nanoparticles (Alg-Fib-PLA-nCMB). Developed sprayable Alg-Fib-PLA-nCMB hydrogel show sustained release of beneficial multi metallic ions at wound site, offering a range of advantages including enhanced cellular function, antibacterial properties, and promotion of crucial wound healing processes like cell migration, ROS mitigation, macrophage polarization, collagen deposition, and vascular regeneration. In a comparative study with a commercial product (Midstress spray), developed Alg-Fib-PLA-nCMB hydrogel demonstrates superior wound healing outcomes in a rat model, indicating its potential for next generation wound care product, addressing critical challenges and offering a promising avenue for future advancements in the wound management.

Multifunctional Bionic Periosteum with Ion Sustained-Release for Bone Regeneration.

In this study, a novel bionic periosteum (BP)-bioactive glass fiber membrane (BGFM) is designed. The introduction of magnesium ion (Mg2+) and zinc ion (Zn2+) change the phase separation during the electrospinning (ES) jet stretching process. The fiber's pore structure transitions from connected to closed pores, resulting in a decrease in the rapid release of metal ions while also improving degradation via reducing filling quality. Additionally, the introduction of magnesium (Mg) and zinc (Zn) lead to the formation of negative charged tetrahedral units (MgO4 2- and ZnO4 2-) in the glass network. These units effectively trap positive charged metal ions, further inhibiting ion release. In vitro experiments reveal that the deigned bionic periosteum regulates the polarization of macrophages toward M2 type, thereby establishing a conducive immune environment for osteogenic differentiation. Bioinformatics analysis indicate that BP enhanced bone repair via the JAK-STAT signaling pathway. The slow release of metal ions from the bionic periosteum can directly enhance osteogenic differentiation and vascularization, thereby accelerating bone regeneration. Finally, the bionic periosteum exhibits remarkable capabilities in angiogenesis and osteogenesis, demonstrating its potential for bone repair in a rat calvarial defect model.

Kornblum Oxidation Reaction-Induced Collective Transformation of Lead Polyhalides for Stable Perovskite Photovoltaics.

The iodide vacancy defects generated during the perovskite crystallization process are a common issue that limits the efficiency and stability of perovskite solar cells (PSCs). Although excessive ionic iodides have been used to compensate for these vacancies, they are not effective in reducing defects through modulating the perovskite crystallization. Moreover, these iodide ions present in the perovskite films can act as interstitial defects, which are detrimental to the stability of the perovskite. Here, an effective approach to suppress the formation of vacancy defects by manipulating the coordination chemistry of lead polyhalides during perovskite crystallization is demonstrated. To achieve this suppression, an α-iodo ketone is introduced to undergo a process of Kornblum oxidation reaction that releases halide ions. This process induces a rapid collective transformation of lead polyhalides during the nucleation process and significantly reduces iodide vacancy defects. As a result, the ion mobility is decreased by one order of magnitude in perovskite film and the PSC achieves significantly improved thermal stability, maintaining 82% of its initial power conversion efficiency at 85 °C for 2800 h. These findings highlight the potential of halide ions released by the Kornblum oxidation reaction, which can be widely used for achieving high-performance perovskite optoelectronics.

Physicochemical properties of AH plus bioceramic sealer, Bio-C Sealer, and ADseal root canal sealer.

BACKGROUND: The aim of this study was to evaluate the physicochemical properties of two newly introduced premixed calcium silicate-based root canal sealers (AH Plus Bioceramic Sealer and Bio-C Sealer) compared to a resin-based root canal sealer (ADseal root canal sealer). METHODS: Solubility, pH analysis, calcium ion release, and film thickness of each sealer were evaluated following ISO guidelines. The data were examined using the two-way ANOVA test. Furthermore, X-ray diffraction (XRD) examination was performed to investigate the crystalline phase of each type of sealer. X-ray fluorescence (XRF) analysis was done for the chemical elemental analysis of each sealer. RESULTS: The least film thickness, highest alkalinity, and highest calcium ion release were all displayed by AH Plus Bioceramic Sealer. High solubility, high alkalinity, intermediate calcium ion release, and intermediate film thickness were all displayed by Bio-C Sealer. While ADseal root canal sealer displayed the greatest film thickness, least solubility, alkalinity, and calcium ion release. CONCLUSIONS: Both AH Plus Bioceramic Sealer and Bio-C Sealer represented adequate properties to be considered a good sealer that could be used as a potential alternative to resin-based root canal sealers.

Release of ions enhanced the antibacterial performance of laser-generated, uncoated Ag nanoparticles.

Identifying the antibacterial mechanisms of elemental silver at the nanoscale remains a significant challenge due to the intertwining behaviors between the particles and their released ions. The open question is which of the above factor dominate the antibacterial behaviors when silver nanoparticles (Ag NPs) with different sizes. Considering the high reactivity of Ag NPs, prior research has primarily concentrated on coated particles, which inevitably hinder the release of Ag+ ions due to additional chemical agents. In this study, we synthesized various Ag NPs, both coated and uncoated, using the laser ablation in liquids (LAL) technique. By analyzing both the changes in particle size and Ag+ ions release, the impacts of various Ag NPs on the cellular activity and morphological changes of gram-negative (E. coil) and gram-positive (S. aureus) bacteria were evaluated. Our findings revealed that for uncoated Ag NPs, smaller particles exhibited greater ions release efficiency and enhanced antibacterial efficacy. Specifically, particles approximately 1.5 nm in size released up to 55 % of their Ag+ ions within 4 h, significantly inhibiting bacterial growth. Additionally, larger particles tended to aggregate on the bacterial cell membrane surface, whereas smaller particles were more likely to be internalized by the bacteria. Notably, treatment with smaller Ag NPs led to more pronounced bacterial morphological changes and elevated levels of intracellular reactive oxygen species (ROS). We proposed that the bactericidal activity of Ag NPs stems from the synergistic effect between particle-cell interaction and the ionic silver, which is dependent on the crucial parameter of particle size.

Evaluating the Translucency, Surface Roughness, and Cytotoxicity of a PMMA Acrylic Denture Base Reinforced with Bioactive Glasses.

The colonisation of the surface of removable acrylic dentures by various types of microorganisms can lead to the development of various diseases. Therefore, the creation of a bioactive material is highly desirable. This study aimed to develop a denture base material designed to release bioactive ions into the oral environment during use. Four types of bioactive glasses (BAG)-S53P4, Biomin F, 45S5, and Biomin C-were incorporated into the PMMA acrylic resin, with each type constituting 20 wt.% (10 wt.% non-silanised and 10% silanised) of the mixture, while PMMA acrylic resin served as the control group. The specimens were subsequently immersed in distilled water, and pH measurements of the aqueous solutions were taken every seven days for a total of 38 days. Additionally, surface roughness and translucency measurements were recorded both after preparation and following seven days of immersion in distilled water. The cytotoxicity of these materials on human fibroblast cells was evaluated after 24 and 48 h using Direct Contact and MTT assays. Ultimately, the elemental composition of the specimens was determined through energy-dispersive X-ray (EDX) spectroscopy. In general, the pH levels of water solutions containing BAG-containing acrylics gradually increased over the storage period, reaching peak values after 10 days. Notably, S53P4 glass exhibited the most significant increase, with pH levels rising from 5.5 to 7.54. Surface roughness exhibited minimal changes upon immersion in distilled water, while a slight decrease in material translucency was observed, except for Biomin C. However, significant differences in surface roughness and translucency were observed among some of the BAG-embedded specimens under both dry and wet conditions. The composition of elements declared by the glass manufacturer was confirmed by EDX analysis. Importantly, cytotoxicity analysis revealed that specimens containing BAGs, when released into the environment, did not adversely affect the growth of human gingival fibroblast cells after 48 h of exposure. This suggests that PMMA acrylics fabricated with BAGs have the potential to release ions into the environment and can be considered biocompatible materials. Further clinical trials are warranted to explore the practical applications of these materials as denture base materials.

Ag-Activated Metal-Organic Framework with Peroxidase-like Activity Synergistic Ag+ Release for Safe Bacterial Eradication and Wound Healing.

Silver nanoparticles (Ag NPs), a commonly used antibacterial nanomaterial, exhibit broad-spectrum antibacterial activity to combat drug-resistant bacteria. However, the Ag NPs often causes a low availability and high toxicity to living bodies due to their easy aggregation and uncontrolled release of Ag+ in the bacterial microenvironment. Here, we report a porous metal-organic framework (MOF)-based Zr-2-amin-1,4-NH2-benzenedicarboxylate@Ag (denoted as UiO-66-NH2-Ag) nanocomposite using an in-situ immobilization strategy where Ag NPs were fixed on the UiO-66-NH2 for improving the dispersion and utilization of Ag NPs. As a result, the reduced use dose of Ag NPs largely improves the biosafety of the UiO-66-NH2-Ag. Meanwhile, after activation by the Ag NPs, the UiO-66-NH2-Ag can act as nanozyme with high peroxidase (POD)-like activity to efficiently catalyze the decomposition of H2O2 to extremely toxic hydroxyl radicals (·OH) in the bacterial microenvironment. Simultaneously, the high POD-like activity synergies with the controllable Ag+ release leads to enhanced reactive oxygen species (ROS) generation, facilitating the death of resistant bacteria. This synergistic antibacterial strategy enables the low concentration (12 µg/mL) of UiO-66-NH2-Ag to achieve highly efficient inactivation of ampicillin-resistant Escherichia coli (AmprE. coli) and endospore-forming Bacillus subtilis (B. subtilis). In vivo results illustrate that the UiO-66-NH2-Ag nanozyme has a safe and accelerated bacteria-infected wound healing.

Direct contact, dissolution and generation of reactive oxygen species: How to optimize the antibacterial effects of layered double hydroxides.

Infections by pathogenic bacteria have been threatening several fields as food industries, agriculture, textile industries and healthcare products. Layered double hydroxides materials (LDHs), also called anionic clays, could be utilized as efficient antibacterial materials due to their several interesting properties such as ease of synthesis, tunable chemical composition, biocompatibility and anion exchange capacity. Pristine LDHs as well as LDH-composites including antibacterial molecules and nanoparticles loaded-LDHs were proven to serve as efficient antibacterial agents against various Gram-positive and Gram-negative bacterial strains. The achieved antibacterial effect was explained by the following mechanisms: (1) Direct contact between the materials and bacterial cells driven by electrostatic interactions between positively charged layers and negatively charged cell membranes, (2) Dissolution and gradual release over time of metallic ions or antibacterial molecules, (3) Generation of reactive oxygen species.

"Gingival Soft Tissue Integrative" Lithium Disilicate Glass-Ceramics with High Mechanical Properties and Sustained-Release Lithium Ions.

Due to their good mechanical performances and high biocompatibility, all-ceramic materials are widely applied in clinics, especially in orthopedic and dental areas. However, the "hard" property negatively affects its integration with "soft" tissue, which greatly limits its application in soft tissue-related areas. For example, dental implant all-ceramic abutments should be well integrated with the surrounding gingival soft tissue to prevent the invasion of bacteria. Mimicking the gingival soft tissue and dentine integration progress, we applied the modified ion-exchange technology to "activate" the biological capacity of lithium disilicate glass-ceramics, via introducing OH- to weaken the stability of Si-O bonds and release lithium ions to promote multi-reparative functions of gingival fibroblasts. The underlying mechanism was found to be closely related to the activation of mitochondrial activity and oxidative phosphorylation. In addition, during the ion-exchange process, the larger radius sodium ions (Na+) replaced the smaller radius lithium ions (Li+), so that the residual compressive stress was applied to the glass-ceramics surface to counteract the tensile stress, thus improving the mechanical properties. This successful case in simultaneous improvement of mechanical properties and biological activities proves the feasibility of developing "soft tissue integrative" all-ceramic materials with high mechanical properties. It proposes a new strategy to develop advanced bioactive and high strength all-ceramic materials by modified ion-exchange, which can pave the way for the extended applications of such all-ceramic materials in soft tissue-related areas.

Development and characterization of experimental ZnO cement containing niobophosphate bioactive glass as filling temporary material.

AIMS: The aim of this study was to develop and characterize a temporary restorative material based on a zinc oxide matrix containing niobophosphate bioactive glass (NbG) for the caries-affected dentin treatment. MATERIAL AND METHODS: NbG was added to a ZnO2 matrix in different concentrations (wt%). EDS-SEM, ATR-FTIR and XRD analyses were performed to characterize the cement. Calcium release was evaluated in TRIS solution after 1, 7 and 14 days by colorimetric method (A650). Compressive strengths and setting times were performed to analyze mechanical properties. RESULTS: EDS spectra confirmed the presence of Ca, P and Nb in the groups containing NbG. EDS mapping exhibit the ZnO2 homogeneous distribution, and NbG immersed in this matrix. Peaks suggesting interaction between matrix and NbG were not detected in Ftir spectra. Calcium releasing showed to be time-dependent for experimental groups containing 10, 20, 30 and 40%. The NbG incorporation progressively increased the compressive strength values in the experimental groups. NbG incorporation seemed to influence the ZnO2 matrix early setting reaction. No statistical difference was observed in the final setting time. CONCLUSION: The addition of NbG particles into zinc oxide matrix could work as a mechanical reinforcement. It is suggested that the calcium released by the cement containing at least 10% NbG could induce apatite formation.

Metal/metal oxide nanocomposites for bactericidal effect: A review.

Many microbial species causing infectious disease all over the world became a social burden and creating threat among community. These microbes possess long lifetime, enhancing mortality and morbidity rate in affected organisms. In this condition, the treatment was ineffective and more chances of spreading of infection into other organisms. Hence, it is necessary to initiate infection control efforts and prevention activities against multidrug resistant microbes, to reduce the death rate of people. Seriously concerning towards this problem progress was shown in developing significant drugs with least side effects. Emergence of nanoparticles and its novelty showed effective role in targeting and destructing microbes well. Further, many research works have shown nanocomposites developed from nanoparticles coupled with other nanoparticles, polymers, carbon material acted as an exotic substance against microbes causing severe loss. However, metal and metal oxide nanocomposites have gained interest due to its small size and enhancing the surface contact with bacteria, producing damage to it. The bactericidal mechanism of metal and metal oxide nanocomposites involve in the production of reactive oxygen species which includes superoxide radical anions, hydrogen peroxide anions and hydrogen peroxide which interact with the cell wall of bacteria causing damage to the cell membrane in turn inhibiting the further growth of cell with leakage of internal cellular components, leading to death of bacteria. This review provides the detailed view on antibacterial activity of metal and metal oxide nanocomposite which possessed novelty due to its physiochemical changes.

Lead release and species transformation of commercial minium pigments in aqueous phase under UV-irradiation.

This study reports the lead ions release and species transformation of minium pigment under UV-irradiation in aqueous phase. The effects of fulvic acid (FA) and pH on lead ions release were investigated. Lower pH and higher FA concentration facilitate the release of lead ions. During photoreaction, electron donors (FA) are provided to scavenge photogenerated holes and enhance the charge separation, leading to the increased lead ions release. When significant amounts of FA exist in the water, they will complex with the released lead ions preferentially. Then, lead ions react with CO2 and proton resulting in the formation of insoluble Pb3(CO3)2(OH)2 after FA consumed. Correspondingly, the dissolved lead ion concentration in water showed a trend of increasing first and then decreasing. Based upon characterization and experimental results, lead ions release and lead species transformation mechanisms of minium were eventually speculated. This research is helpful for better understanding the environmental behavior and risk of semiconductor pigments in natural water.

Development and characterization of self-etching adhesives doped with 45S5 and niobophosphate bioactive glasses: Physicochemical, mechanical, bioactivity and interface properties.

OBJECTIVE: The aim of study was to develop and characterize experimental bioactive glasses (45S5 and niobophosphate bioactive glass (NbG)) and evaluate the effects of their addition in self-etching adhesive systems on physicochemical, mechanical, and bioactive properties, microtensile bond strength (µTBS), and nanoleakage (NL). METHODS: Two-step self-etching adhesive systems containing 5, 10, and 20 wt.% of 45S5 and NbG bioactive glasses were developed. An experimental adhesive without microparticles and a commercial adhesive (Clearfil SE Bond) were used as control groups. The materials were evaluated for their degree of conversion (DC%), ultimate tensile strength (UTS), softening in solvent, radiopacity, sorption and solubility, alkalizing activity (pH), ionic release, and bioactivity. µTBS and NL were evaluated after 24 h and 1 year of storage. The data were subjected to analysis of variance and post-Holm-Sidak tests (α = 0.05). RESULTS: The addition of the two bioactive glasses did not change the values of the degree of conversion, ultimate tensile strength, and softening in solvent. The adhesive system containing 20% NbG showed the highest radiopacity. The incorporation of 45S5 increased water sorption and solubility, raised the pH, and allowed the release of large amounts of calcium. After 28 days of immersion in simulated body fluid, the 45S5 adhesive precipitated hydroxyapatite and calcium carbonate (SEM/EDX, ATR/FTIR, and XDR). The addition of 45S5 and NbG to the adhesives improved the stability of the resin-dentin interface after 1 year. SIGNIFICANCE: The incorporation of microparticles from 45S5 bioactive glass in self-etching adhesive systems is considered an excellent alternative for the development of a bioactive adhesive that improves the integrity of the hybrid layer on sound dentin.

Metal chloride-loaded biochar for phosphorus recovery: Noteworthy roles of inherent minerals in precursor.

Phosphorus (P) is a valuable resource, while it is vastly lost with wastewater causing eutrophication. In this study, to recover P, composite biochars were prepared by pyrolyzing biowaste impregnated with FeCl3 or MgCl2. It was found that inherent mineral profiles in the biowastes played important roles in interacting with metal chlorides and determined P sorption and precipitation. Specifically, two biowastes containing distinct mineral contents, sawdust and sediment, were selected as model components, being alone or mixed at 1:1 (w/w) to prepare biochars with low, moderate and high mineral contents. Results showed that biochar itself could not absorb P, while loading FeCl3 or MgCl2 achieved P recovery rates of approximate 60-100% and 50-100%, respectively, via electrostatic attraction or ligand exchange of PO43- with -OH/-COOH, which was attributed to the enhanced positive charges and -OH/-COOH on the materials by these metal chlorides. Inherent minerals inhibited FeCl3 transforming into Fe3O4 in pyrolysis and promoted generation of Fe4(PO4)3(OH)3 in P sorption, thus high-mineral content was more appropriate for FeCl3 loading; however, precursors with low-mineral content was suitable for MgCl2 loading, since the bulk-C in biochar acted as porous structure to support MgO crystals with high superficial area (∼255.85 m2 g-1). Besides, FeCl3 and MgCl2 both drove dissolution of inherent minerals significantly, while inherent minerals inhibited release of soluble Fe and Mg2+ into solution, which minimized secondary pollution. This study implied that in constructing composite biochar for catching P, the type of metal chloride should match the inherent minerals in biowastes to maximize P recovery and minimize secondary pollution.

Advanced Mg, Zn, Sr, Si Multi-Substituted Hydroxyapatites for Bone Regeneration.

PURPOSE: Compositional tailoring is gaining more attention in the development of advanced biomimetic nanomaterials. In this study, we aimed to prepare advanced multi-substituted hydroxyapatites (ms-HAPs), which show similarity with the inorganic phase of bones and might have therapeutic potential for bone regeneration. MATERIALS: Novel nano hydroxyapatites substituted simultaneously with divalent cations: Mg2+ (1.5%), Zn2+ (0.2%), Sr2+ (5% and 10%), and Si (0.2%) as orthosilicate (SiO4 4-) were designed and successfully synthesized for the first time. METHODS: The ms-HAPs were obtained via a wet-chemistry precipitation route without the use of surfactants, which is a safe and ecologically friendly method. The composition of synthesized materials was determined by inductively coupled plasma optical emission spectrometry (ICP-OES). The materials were characterized by X-ray powder diffraction (XRD), FT-IR and FT-Raman spectroscopy, BET measurements and by imaging techniques using high-resolution TEM (HR-TEM), FE-SEM coupled with EDX, and atomic force microscopy (AFM). The ion release was measured in water and in simulated body fluid (SBF). RESULTS: Characterization methods confirmed the presence of the unique phase of pure stoichiometric HAP structure and high compositional purity of all synthesized nanomaterials. The doping elements influenced the crystallite size, the crystallinity, lattice parameters, morphology, particle size and shape, specific surface area, and porosity. Results showed a decrease in both nanoparticle size and crystallinity degree, coupled with an increase in specific surface area of these advanced ms-HAP materials, in comparison with pure stoichiometric HAP. The release of biologically important ions was confirmed in different liquid media, both in static and simulated dynamic conditions. CONCLUSION: The incorporation of the four substituting elements into the HAP structure is demonstrated. Synthesized nanostructured ms-HAP materials might inherit the in vivo effects of substituting functional elements and properties of hydroxyapatite for bone healing and regeneration. Results revealed a rational tailoring approach for the design of a next generation of bioactive ms-HAPs as promising candidates for bone regeneration.

Fabrication and characterization of remineralizing dental composites containing hydroxyapatite nanoparticles.

The aim of this study was to fabricate and characterize dental composites containing hydroxyapatite nanoparticles (HApNPs). Four dental composites were produced from the same organic matrix (70 wt% Bis-GMA and 30 wt% TEGDMA), with partial replacement of BaBSi particles (65 wt%) by HApNPs in the following concentrations (wt%): E0 (0) - control, E10 (10), E20 (20) and E30 (30). Ca2+ and PO43- release was evaluated in solutions with different pHs (4, 5.5, and 7) using atomic emission spectroscopy with microwave-induced nitrogen plasma while the enamel remineralization potential was evaluated in caries-like enamel lesions induced by S. mutans biofilm using micro-CT. The following properties were characterized: degree of conversion (DC%), microhardness (KHN), flexural strength (FS), elastic modulus (EM) and translucency (TP). The higher the HApNPs content, the higher the Ca2+ and PO43- release. The ions release was influenced by pH (4 > 5.5 > 7) (p < 0.05). All composites loaded with HApNPs were able to remineralize the enamel (E30 = E20 > E10) (p < 0.05). Contrarily, E0 was not able of recovering the enamel mineral loss. E0 and E10 presented highest DC%, while E20 and E30 showed similar and lowest DC%. KHN and FS were decreased with the addition of HApNPs, while EM was not influenced by the incorporation of HApNPs. E10 presented statistically similar TP to E0, while this property decreased for E20 and E30 (p < 0.05). Incorporation of HApNPs into dental composites promoted enamel remineralization, mainly at potentially cariogenic pH (= 4), while maintained their overall performance in terms of physicomechanical properties.

Copper Oxide Nanoparticles Induce Oxidative DNA Damage and Cell Death via Copper Ion-Mediated P38 MAPK Activation in Vascular Endothelial Cells.

BACKGROUND: Inhaled nanoparticles can cross pulmonary air-blood barrier into circulation and cause vascular endothelial injury and progression of cardiovascular disease. However, the molecular mechanism underlying the vascular toxicity of copper oxide nanoparticles (CuONPs) remains unclear. We have recently demonstrated that the release of copper ions and the accumulation of superoxide anions contributed to CuONPs-induced cell death in human umbilical vein endothelial cells (HUVECs). Herein, we further demonstrate the mechanism underlying copper ions-induced cell death in HUVECs. METHODS AND RESULTS: CuONPs were suspended in culture medium and vigorously vortexed for several seconds before exposure. After treatment with CuONPs, HUVECs were collected, and cell function assays were conducted to elucidate cellular processes including cell viability, oxidative stress, DNA damage and cell signaling pathways. We demonstrated that CuONPs uptake induced DNA damage in HUVECs as evidenced by γH2AX foci formation and increased phosphorylation levels of ATR, ATM, p53 and H2AX. Meanwhile, we showed that CuONPs exposure induced oxidative stress, indicated by the increase of cellular levels of superoxide anions, the upregulation of protein levels of heme oxygenase-1 (HO-1) and glutamate-cysteine ligase modifier subunit (GCLM), the elevation of the levels of malondialdehyde (MDA), but the reduction of glutathione to glutathione disulfide ratio. We also found that antioxidant N-acetyl-L-cysteine (NAC) could ameliorate CuONPs-induced oxidative stress and cell death. Interestingly, we demonstrated that p38 mitogen-activated protein kinase (MAPK) signaling pathway was activated in CuONPs-treated HUVECs, while p38α MAPK knockdown by siRNA significantly rescued HUVECs from CuONPs-induced DNA damage and cell death. Importantly, we showed that copper ions chelator tetrathiomolybdate (TTM) could alleviate CuONPs-induced oxidative stress, DNA damage, p38 MAPK pathway activation and cell death in HUVECs. CONCLUSION: We demonstrated that CuONPs induced oxidative DNA damage and cell death via copper ions-mediated p38 MAPK activation in HUVECs, suggesting that the release of copper ions was the upstream activator for CuONPs-induced vascular endothelial toxicity, and the copper ions chelator TTM can alleviate CuONPs-associated cardiovascular disease.