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The constantly increasing demand of Rare Earth Elements (REEs) made them to be part of the so-called "critical elements" indispensable for the energy transition. The monopoly of only a few countries, the so-called balance problem between demand and natural abundance, and the need to limit the environmental costs of their mining, stress the necessity of a recycling policy of these elements. Different methods have been tested for REEs recovery. Despite the well-known ion-exchange properties of zeolites, just few preliminary works investigated their application for REEs separation and recycle. In this work we present a double ion exchange experiment on a NH 4 -13X zeolite, aimed at the recovery of different REEs from solutions mimicking the composition of liquors obtained from the leaching of spent fluorescent lamps. The results showed that the zeolite was able to exchange all the REEs tested, but the exchange capacity was different: despite Y being the more concentrated REE in the solutions, the cation exchange was lower than less concentrated ones (16 atoms p.u.c. vs 21 atoms for Ce and La solutions), suggesting a possible selectivity. In order to recover REEs from the zeolite, a second exchange with an ammonium solution was performed. The analyses of the zeolites show that almost all of Ce and Eu remain in the zeolite, while nearly half of La and Y are released. This, once again, suggests a possible selective release of REEs and open the possibility for a recovery process in which Rare Earths can be effectively separated., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Considering the increase in patients who suffer from osteoporosis and the bone defects that occur in these patients, bone tissue regeneration is a promising option to solve this problem. To achieve a synergistic effect between the synthesis of a proper structure and bioactive/pharmaceutical activity, ions with a physiological effect can be added to silica structures, such as Ca 2+ , thanks to its bioactive behavior, and Ga 3+ for its antibacterial and anticancer action. In this work, the synthesis of large pore mesoporous silica (LPMS), potential bioactive glasses containing Ca 2+ and Ga 3+ , has been studied. Corresponding structures, in terms of composition, have been synthesized following the Sol-Gel EISA (Evaporation Induced Self-Assembly) process (obtaining Classical Mesoporous Silica, MS). Pore structure characterization of LPMSs and MSs has been performed using N 2 adsorption/desorption and Hg-porosimetry, showing the presence of pores for LPMSs in the range of 20-60 and 200-600 nm. Nisin, a polycyclic antibacterial peptide, has been used for load tests. The load and release tests performed highlight a higher loading and releasing, doubled for LPMSs if compared to MSs. To confirm the maintenance of the structure of LPMSs and their mechanical strength and resistance, scanning electron microscopy images were acquired before and after release tests. Ca and Ga release in SBF has been studied through inductively coupled plasma-optical emission spectroscopy (ICP-OES), showing a particularly high release of these ions performed with LPMSs. The bioactive behavior of Ca-containing structures has been confirmed using FT-IR (Fourier-transform infrared spectroscopy), SEM-EDS (Scanning Electron Microscope-Energy Dispersive Spectroscopy), and X-ray powder diffraction (XRDP). In conclusion, LPMSs showed better loading and releasing properties compared with classical MS and better release in terms of active ions. In addition, it has also been demonstrated that LPMSs have bioactive behavior (a well-known characteristic of MSs).

The synthesis of a scaffold that can accommodate big molecules with a pharmaceutical role is important to shield them and maintain their biological activity. In this field, silica particles with large pores (LPMS) are innovative supports. Large pores allow for the loading of bioactive molecules inside the structure and contemporarily their stabilization and protection. These purposes cannot be achieved using classical mesoporous silica (MS, pore size 2-5 nm), because their pores are not big enough and pore blocking occurs. LPMSs with different porous structures are synthesized starting from an acidic water solution of tetraethyl orthosilicate reacting with pore agents (Pluronic ® F127 and mesitylene), performing hydrothermal and microwave-assisted reactions. Time and surfactant optimization were performed. Loading tests were conducted using Nisin as a reference molecule (polycyclic antibacterial peptide, with dimensions of 4-6 nm); UV-Vis analyses on loading solutions were performed. For LPMSs, a significantly higher loading efficiency (LE%) was registered. Other analyses (Elemental Analysis, Thermogravimetric Analysis and UV-Vis) confirmed the presence of Nisin in all the structures and its stability when loaded on them. LPMSs showed a lower decrease in specific surface area if compared to MS; in terms of the difference in LE% between samples, it is explained considering the filling of pores for LPMSs, a phenomenon that is not allowed for MSs. Release studies in simulated body fluid highlight, only for LPMSs, a controlled release, considering the longer time scale of release. Scanning Electron Microscopy images acquired before and after release tests shows the LPMSs' maintenance of the structure, demonstrating strength and mechanical resistance of structures. In conclusion, LPMSs were synthesized, performing time and surfactant optimization. LPMSs showed better loading and releasing properties with respect to classical MS. All collected data confirm a pore blocking for MS and an in-pore loading for LPMS.

Cancer is a leading cause of death worldwide, its genesis and progression are caused by homeostatic errors, and reactive oxygen species play a major role in promoting aberrant cancer homeostasis. In this scenario, curcumin could be an interesting candidate due to its versatile antioxidant, anti-inflammatory, anti-tumor, anti-HIV, and anti-infection properties. Nonetheless, the major problem related to its use is its poor oral bioavailability, which can be overcome by encapsulating it into small particles, such as hydrogel beads containing mesoporous silica. In this work, various systems have been synthesized: starting from mesoporous silica glasses (MGs), cerium-containing MGs have been produced; then, these systems have been loaded with 4 to 6% of curcumin. Finally, various MGs at different compositions have been included in alginate beads. In vitro studies showed that these hybrid materials enable the stabilization and effective delivery of curcumin and that a synergic effect can be achieved if Ce 3+ /Ce 4+ and curcumin are both part of the beads. From swelling tests, it is possible to confirm a controlled curcumin release compartmentalized into the gastrointestinal tract. For all beads obtained, a curcumin release sufficient to achieve the antioxidant threshold has been reached, and a synergic effect of cerium and curcumin is observed. Moreover, from catalase mimetic activity tests, we confirm the well-known catalytic activity of the couple Ce 3+ /Ce 4+ . In addition, an extremely good radical scavenging effect of curcumin has been demonstrated. In conclusion, these systems, able to promote an enzymatic-like activity, can be used as drug delivery systems for curcumin-targeted dosing., Competing Interests: The authors declare no conflict of interest

Curcumin is known for its therapeutic properties; among these, antioxidant, anti-inflammatory and anti-cancer ones stand out. Besides, curcumin metal complexes have shown widespread application in medicine and can be exploited as lead structures for developing metal-based drugs. Unfortunately, curcumin is poorly bioavailable, mainly due to its instability in physiological conditions; this weakness is tightly connected to the presence of the β-diketo moiety undergoing tautomeric equilibrium. Stability and metal-chelating ability can be tuned by modulating the electronic effects and steric hindrance close to the β-diketo moiety; in addition, formation of a metal complex shifts the tautomeric equilibrium towards the β-keto-enol form and increases stability in biological media. Among the metals used in clinical therapy, gallium nitrate has shown to have significant antitumor activity against non-Hodgkin lymphoma and bladder cancer, thus indicating that gallium-based drugs have potential for further development as antineoplastic agents with improved therapeutic activity. Curcuminoids have demonstrated high affinity for gallium(III), allowing the formation of stable positively charged M:L 1:2 β-diketonate complexes that benefit from the therapeutic activity of both the metal and the ligand. Seven new curcumin derivatives were synthesized and completely characterized. The new derivatives retain the solvent-dependent keto-enol tautomerism, with the prevalence of the diketo form in aqueous solution. Enhanced stability in simulated physiological conditions was observed in comparison to the lead compound curcumin. The presence of Ga 3+ anticipates the dissociation of the enolic proton, allowing chelate complex formation, and simultaneously it shifts the tautomeric equilibrium towards the keto-enol form. A complete 1 H/ 13 C NMR and UV-Vis study was performed to define the metal-to-ligand stoichiometry ratio and the overall stability constants. In addition, we demonstrated that some of the derivatives have increased antiproliferative activity on colon cancer cells compared to curcumin and antioxidant properties. On the whole, the synthesized curcumin-based molecules may act as new gallium(III) chelators with improved stability with respect to curcumin and could open interesting perspectives for the development of novel therapeutic agents for cancer.

Bioactive glasses (BGs) for biomedical applications are doped with therapeutic inorganic ions (TIIs) in order to improve their performance and reduce the side effects related to the surgical implant. Recent literature in the field shows a rekindled interest toward rare earth elements, in particular cerium, and their catalytic properties. Cerium-doped bioactive glasses (Ce-BGs) differ in compositions, synthetic methods, features, and in vitro assessment. This review provides an overview on the recent development of Ce-BGs for biomedical applications and on the evaluation of their bioactivity, cytocompatibility, antibacterial, antioxidant, and osteogenic and angiogenic properties as a function of their composition and physicochemical parameters.

(1) Background: a cell evaluation focused to verify the self-regenerative antioxidant activity is performed on cerium doped bioactive glasses. (2) Methods: the glasses based on 45S5 Bioglass ® , are doped with 1.2 mol%, 3.6 mol% and 5.3 mol% of CeO 2 and possess a polyhedral shape (~500 µm 2 ). Glasses with this composition inhibit oxidative stress by mimicking catalase enzyme (CAT) and superoxide dismutase (SOD) activities; moreover, our previous cytocompatibility tests (neutral red (NR), 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and Bromo-2-deoxyUridine (BrdU)) reveal that the presence of cerium promotes the absorption and vitality of the cells. The same cytocompatibility tests were performed and repeated, in two different periods (named first and second use), separated from each other by four months. (3) Results: in the first and second use, NR tests indicate that the presence of cerium promotes once again cell uptake and viability, especially after 72 h. A decrease in cell proliferation it is observed after MTT and BrdU tests only in the second use. These findings are supported by statistically significant results (4) Conclusions: these glasses show enhanced proliferation, both in the short and in the long term, and for the first time such large dimensions are studied for this kind of study. A future prospective is the implantation of these bioactive glasses as bone substitute in animal models.

Salen-type metal complexes have been actively studied for their nonlinear optical (NLO) properties, and push-pull compounds with charge asymmetry generated by electron releasing and withdrawing groups have shown promising results. As a continuation of our research in this field and aiming at solid-state features, herein we report on the synthesis of mononuclear copper(II) derivatives bearing either tridentate N 2 O Schiff bases L (a-c)- and pyridine as the forth ancillary ligand, [Cu(L a-c )(py)](ClO 4 ) ( 1a - c ), or unsymmetrically-substituted push-pull tetradentate N 2 O 2 Schiff base ligands, [Cu(5-A-5'-D-saldpen/chxn)] ( 2a - c ), both derived from 5-substituted salicylaldehydes (sal) and the diamines (1 R ,2 R )-1,2-diphenylethanediamine (dpen) and (1 S ,2 S )-1,2-diaminocyclohexane (chxn). All compounds were characterized through elemental analysis, infrared and UV/visible spectroscopies, and mass spectrometry in order to guarantee their purity and assess their charge transfer properties. The structures of 1a - c were determined via single-crystal X-ray diffraction studies. The geometries of cations of 1a - c and of molecules 2a - c were optimized through DFT calculations. The solid-state NLO behavior was measured by the Kurtz-Perry powder technique @1.907 µm. All chiral derivatives possess non-zero quadratic electric susceptibility ( χ (2) ) and an efficiency of about 0.15-0.45 times that of standard urea.

The cytocompatibility of potential bioactive cerium-containing (Ce 3+ /Ce 4+ ) glasses is here investigated by preparing three different glasses with increasing amount of doping CeO₂ (1.2, 3.6 and 5.3 mol% of CeO₂, called BG_1.2, BG_3.6 and BG_5.3, respectively) based on 45S5 Bioglass® (called BG). These materials were characterized by Environmental Scanning Electron Microscopy (ESEM) and infrared spectroscopy (FTIR) after performing bioactivity tests in Dulbecco's Modified Eagle Medium (DMEM) solution, and the ions released in solution were determined by Inductively Coupled Plasma Mass Spectrometry (ICP-MS) and Optical Emission Spectrometry (ICP-OES). The data obtained clearly show that the glass surfaces of BG, BG_1.2 and BG_3.6 were covered by hydroxyapatite (HA), while BG_5.3 favored the formation of a cerium phosphate crystal phase. The cytotoxicity tests were performed using both murine long bone osteocyte-like (MLO-Y4) and mouse embryonic fibroblast (NIH/3T3) cell lines. The cerium-containing bioactive glasses show an increment in cell viability with respect to BG, and at long times, no cell aggregation and deformation were observed. The proliferation of NIH/3T3 cells increased with the cerium content in the glasses; in particular, BG_3.6 and BG_5.3 showed a higher proliferation of cells than the negative control. These results highlight and enforce the proposal of cerium-doped bioactive glasses as a new class of biomaterials for hard-tissue applications.

The phosphors of formula Ba₅Si₈O 21 :Eu 2+ ,Dy 3+ were synthesized and studied in order to improve their properties. Their synthesis conditions were evaluated as a function of precursors, crucible composition, flux agents, dopants and temperatures. The samples were characterised by means of a systematic investigation through elemental, kinetic, mineralogical (both qualitative and quantitative), and morphological analysis. This study allows for a careful evaluation of the parameters that influence the formation and properties of Ba₅Si₈O 21 :Eu 2+ ,Dy 3+ phosphors. As for the synthesis conditions, the use of Na₂SiO₃, BaCO₃ and NH₄Cl as precursors was very important to reduce the temperature and time of synthesis. The reducing atmosphere produced with purified coal was cheaper and gave results similar to the more traditional gas mixture (H₂/N₂). At the end of this study, a phosphor with improved long persistent phosphorescence (LPP) characteristics was obtained with Ba/Si = 0.7, Eu/Si = 2.8 × 10 -3 and Dy/Si = 3.6 × 10 -3 following a 6 h-synthesis in a quartz crucible., Competing Interests: The authors declare no conflict of interest.

The addition of cerium oxide to bioactive glasses, important materials for bone tissue regeneration, has been shown to induce multifunctionality, combining a significant bioactivity with antioxidant properties. We provide a real time investigation of the evolution of the electronic properties of highly diluted cerium ions in a liquid environment containing hydrogen peroxide - the most abundant reactive oxygen species in living cells. This challenging task is undertaken by means of high-energy resolution fluorescence detected by X-ray absorption near-edge spectroscopy at the Ce L3 edge. We investigate samples with variable compositions and different morphologies. We relate the observed spectroscopic changes not only to variations in the concentration of the two Ce oxidation states in the samples, but also to changes in the local atomic environment of Ce ions, providing a clear picture of the role of cerium ions in the dissociation of hydrogen peroxide. The obtained results contribute to the understanding of the mechanisms that come into play in the process and provide a basis for the optimization of the functionalities of this class of materials.

Beneficial effects in bone cell growth and antibacterial action are currently attributed to Ga 3+ ions. Thus, they can be used to upgrade mesoporous bioactive glasses (MBGs), investigated for tissue engineering, whenever they released therapeutic amounts of gallium ions to the surrounding medium. Three gallium-enriched MBGs with composition (in mol %) x SiO₂- y CaO- z P₂O₅-5Ga₂O₃, being x = 70, y = 15, z = 10 for Ga_1 ; x = 80, y = 12, z = 3 for Ga_2 ; and x = 80, y = 15, z = 0 for Ga_3 , were investigated and compared with the gallium-free 80SiO₂-15CaO-5P₂O₅ MBG ( B ). 29 Si and 31 P MAS NMR analyses indicated that Ga 3+ acts as network modifier in the glass regions with higher polymerization degree and as network former in the zones with high concentration of classical modifiers (Ca 2+ ions). Ga_1 and Ga_2 exhibited a quick in vitro bioactive response because they were coated by an apatite-like layer after 1 and 3 days in simulated body fluid. Although we have not conducted biological tests in this paper (cells or bacteria), Ga_1 released high but non-cytotoxic amounts of Ga 3+ ions in Todd Hewitt Broth culture medium that were 140 times higher than the IC90 of Pseudomonas aeruginosa bacteria, demonstrating its potential for tissue engineering applications., Competing Interests: The authors declare no conflict of interest.

In this paper, we report the study of the loading and the release of curcuminoids by bioactive glasses (BG) and mesoporous bioactive glasses (MBG). Through a detailed spectroscopic study, it was possible to determine the amount and the type of molecules released in water and in simulated body fluid (SBF). In particular, curcumin and K2T21 show a good ability to be released in di-keto and keto-enolic form, depending from the pH. However, after 24 h, the amount of pristine curcumin release is very low with a consequent increment of degradation products derived by curcuminoids. The presence of -OH groups on curcuminoids is a fundamental pre-requisite in order to obtain a high loading and release in polar solution such as water and SBF. The substrate on which we loaded the drugs does not seem to affect significantly the loading and the release of the drugs. The environment, instead, affects the release: for all the drugs, the release in SBF, buffered at pH of 7.4, is slightly worse than the release in water (basic pH values).

The ability of Ce-containing bioactive glasses to inhibit oxidative stress in terms of reduction of hydrogen peroxide, by mimicking the catalase enzyme activity is demonstrated here for the first time. The antioxidant properties of three bioactive glasses containing an increasing amount of CeO2 have been evaluated by following the degradation of hydrogen peroxide with time after immersion in H2O2 aqueous solutions with different concentration. XPS and UV-vis measurements allowed us to determine the Ce(3+)/Ce(4+) ratio in the bulk and on the glass surface, and to correlate it with the ability of the samples to show catalase mimetic activity. Interestingly, we have found that the bioactive glass with composition 23.2Na2O-25.7CaO-43.4SiO2-2.4P2O5-5.3CeO2 immersed in 0.1 M H2O2 aqueous solution is able to degrade 90% of it in 1 week. The reduction in bioactivity of the glasses with increasing CeO2 content is here rationalized in terms of a lower amount of phosphate groups available for the hydroxyapatite layer formation, after binding with cerium ions. In fact, classical molecular dynamics simulations revealed that the addition of CeO2 leads to the formation of cerium phosphate rich regions. The formation of an insoluble CePO4 crystalline phase is also observed by XRD analysis after thermal treatment of the glass samples.

Bioceramics, such as silica-based glasses, are widely used in bone and teeth restoration. Nowadays, the association between nanotechnology and pharmacology is one of the most promising research fields in cancer therapy. The advanced processing methods and new chemical strategies allow the incorporation of drugs within them or on their functionalized surfaces. Bioceramics can act as local drug delivery systems to treat bone and teeth diseases. The present paper reports data related to the development of a pH-stimuli responsive bioactive glass. The glass conjugation with 5-aminofluorescein (5-AF), through a pH-sensitive organic spacer, allows to produce a pH-responsive bioactive biomaterial: when it is exposed to specific pH changes, it can favour the release of 5-AF directly at the target site. 5-AF has been chosen as a simple, low cost, non toxic model to simulate doxorubicin, an anticancer drug. As doxorubicin, 5-AF contains an amino group in its structure in order to form an amide bond with the carboxylic functionalities of the glass. Raman spectroscopy and thermal analysis confirm the glass conjugation of 5-AF by means of an amide bond; the amount of 5-AF loaded was very high (≈ 65 and 44 wt%). The release tests at two different pH (4.2 and 7.4) show that the amount of released 5-AF is higher at acid pH with respect to physiological one. This preliminary datum evidenced that a pH-sensitive drug delivery system has been developed. The low amount of 5-AF released (<1 wt% of the total 5-AF) is due to the very low solubility of 5-AF in aqueous medium. This disadvantage, may be overcome in a dynamic environment (physiological conditions), where it is possible to obtain a drug release system ensuring an effective therapeutic dose for long times and, at the same time, avoiding the drug toxicity.

Zn 2+ ions exhibit osteogenic, angiogenic and antimicrobial properties. For this reason, they are often added in small amounts to bioceramics being investigated for bone tissue engineering. In this paper, the cytocompatibility and antibacterial properties of 80% SiO 2 -15% CaO-5% P 2 O 5 (mol%) mesoporous bioactive glass (MBG) scaffolds substituted with 4.0% and 7.0% of ZnO were studied and compared with the Zn-free scaffold. Cell proliferation, morphology, differentiation and cytotoxic effects of Zn 2+ ions released from the samples were examined by culturing human osteoblast-like cells (HOS) osteoblasts both in the presence of sample extracts and on the scaffold surface. The bacterial inhibition capacity of the scaffolds was explored by using Gram-positive Stapylococcus aureus bacteria, responsible for numerous infections in orthopedic surgery, to simulate a severe infection. Our results show that the Zn-MBG scaffolds possess a hierarchical meso-macropore structure suitable for osteoblast growth. Furthermore, the amount of Zn 2+ released from the scaffold with 4.0% ZnO was found to be more favorable for HOS cell development than that released from the scaffold including 7.0% ZnO. Zn 2+ released to the medium from both scaffolds exhibited antibacterial properties against S. aureus. Thus, the cytocompatibility and the antibacterial ability exhibited by the MBG scaffold containing 4.0% ZnO make it a suitable candidate for bone regeneration applications.

The aim of the present contribution is to prepare a functionalized bioactive glass potentially useful as prosthetic material, but also able to release organic molecules in response to a change of the pH environment. By this approach it is possible to develop devices which can be used for a triggered drug release in response to specific stimuli; this is an attractive research field, in order to avoid either systemic and/or local toxic effects of drugs. In particular, in the present paper we report data related to the development of a new formulation of bioactive glasses, their functionalization with organic molecules to obtain a pH-sensitive bond, their physicochemical characterization and in vitro bioactivity in simulated biological fluids (SBF), and organic molecule delivery tests at different pH. The glass functionalization, by means of a covalent reaction, allows us to produce a model of pH-responsive bioactive biomaterial: when it is exposed to specific pH changes, it can favor the release of the organic molecules directly at the target site. Cysteamine and 5-aminofluorescein are used as model molecules to simulate a drug. The materials, before and after the different functionalization steps and in vitro release tests at different pH, have been characterized by means of different experimental techniques such as X-ray powder diffraction (XRPD), Raman, FTIR and fluorescence spectroscopies, N2 adsorption, thermogravimetric (TGA) and elemental analysis.

A gallium containing glass 45.7SiO2·24.1Na2O·26.6CaO·2.6P2O5·1.0Ga2O3 (referred to as "Ga1.0") and a parent Ga-free glass 46.2SiO2·24.3Na2O·26.9CaO·2.6P2O5 (hereinafter represented as "H"), corresponding to Bioglass® 45S5, were functionalized with Tetraethoxysilane (TEOS) and (3-Aminopropyl)triethoxysilane (APTS) in order to improve their ability to bond with biomolecules, such as drugs, proteins, and peptides. Functionalization with TEOS and APTS promoted the increment in OH groups and formation of NH2 groups on the glass surface, respectively. The presence of OH or NH2 groups was investigated by means of IR spectroscopy and elemental analysis. Moreover, in vitro study of these functionalized glasses was performed in simulated body fluid (SBF) so as to investigate the effect of functionalization on the bioactive behavior of H and Ga1.0. The results showed that the functionalization was obtained along with maintaining their bioactivity. The surfaces of both functionalized glasses were covered by a layer of apatite within 30 days of SBF immersion. In addition, CaCO3 was also identified on the surface of APTS functionalized glasses. However, no gallium release was detected during SBF soaking., (Copyright © 2013 Elsevier B.V. All rights reserved.)

The structural properties of phosphosilicate glasses based on the 45S5 Bioglass doped with gallium and aluminum (46.2 SiO2·24.3Na2O·26.9CaO·2.6P2O5·1.0X2O3, X = Ga or Al) are investigated by means of classical molecular dynamics simulations. Structural features of the two compositions are compared with those of the original 45S5 Bioglass in order to relate them to the different known bioactivities of these materials. Differences in the coordination environments of Ga and Al, network connectivity, and ion aggregation reveal a microscopic model of these glasses which supports the interpretation of the experimental data and provides new insight into the different biological behaviors of Ga- and Al-containing phosphosilicate glasses. Although Ga is found predominantly in a 4-fold coordination environment, small amounts of 5- and 6-fold coordinated atoms have been detected depending on the interatomic potential model employed. This suggests its possible intermediate role in phosphosilicate glasses. On the contrary, Al plays a network former role and leads to glasses with a more polymerized structure. Interestingly, the results show an increased propensity for aggregation of the Ca(2+) and PO4(3-) ions in the Al-containing phosphosilicate glasses with respect to the Ga-containing ones. This leads to insoluble calcium-phosphate-rich regions not detected in the bioactive glasses.

A series of Sr-substituted hydroxyapatites (HA), of general formula Ca(10-x)Srx(PO4)6(OH)2, where x=2 and 4, were synthesized by solid state methods and characterized extensively. The reactivity of these materials in cell culture medium was evaluated, and the behavior towards MG-63 osteoblast cells (in terms of cytotoxicity and proliferation assays) was studied. Future in vivo studies will give further insights into the behavior of the materials. A paper by Lagergren et al. (1975), concerning Sr-substituted HA prepared by a solid state method, reports that the presence of Sr in the apatite composition strongly influences the apatite diffraction patterns. Zeglinsky et al. (2012) investigated Sr-substituted HA by ab initio methods and Rietveld analyses and reported changes in the HA unit cell volume and shape due to the Sr addition. To further clarify the role played by the addition of Sr on the physico-chemical properties of these materials we prepared Sr-substituted HA compositions by a solid state method, using different reagents, thermal treatments and a multi-technique approach. Our results indicated that the introduction of Sr at the levels considered here does influence the structure of HA. There is also evidence of a decrease in the crystallinity degree of the materials upon Sr addition. The introduction of increasing amounts of Sr into the HA composition causes a decrease in the specific surface area and an enrichment of Sr-apatite phase at the surface of the samples. Bioactivity tests show that the presence of Sr causes changes in particle size and/or morphology during soaking in MEM solution; on the contrary the morphology of pure HA does not change after 14 days of reaction. The presence of Sr, as Sr-substituted HA and SrCl2, in cultures of human MG-63 osteoblasts did not produce any cytotoxic effect. In fact, Sr-substituted HA increased the proliferation of osteoblast cells and enhanced cell differentiation: Sr in HA has a positive effect on MG-63 cells. In contrast, Sr ions alone, at the concentrations released by Sr-HA (1.21-3.24 ppm), influenced neither cell proliferation nor differentiation. Thus the positive effects of Sr in Sr-HA materials are probably due to the co-action of other ions such as Ca and P., (Copyright © 2012 Elsevier B.V. All rights reserved.)

A new melted bioactive system containing gold nanoparticles (AuNPs) was prepared exploiting a post-synthesis thermal treatment that allows one to modify crystal phases and nature, shape and distribution of the gold species in the glass-ceramic matrix as evidenced by UV-visible spectroscopy, transmission electron microscopy and powder X-ray diffraction analysis. In human MG-63 osteoblasts the presence of Au(n)(+) species caused an increase of lactate dehydrogenase leakage and malonyldialdehyde production, whereas Hench's Bioglass HAu-600-17 containing only AuNPs did not cause any effect. In addition, HAu-600-17 caused in vitro hydroxyapatite formation and an increase of specific surface area with a controlled release of gold species; this material is then suitable to be used as a model system for the controlled delivery of nanoparticles.

Mesoporous bioactive glass scaffolds (MBG&#95;Scs), based on 80% SiO(2)-15% CaO-5% P(2)O(5) (in mol.%) mesoporous sol-gel glasses substituted with Ce(2)O(3), Ga(2)O(3) (both 0.2% or 1.0%) and ZnO (0.4% or 2.0%), were synthesized by combination of evaporation-induced self-assembly and rapid prototyping techniques. Cerium, gallium and zinc trace elements were selected because of their inherent beneficial biological properties. Fabricated scaffolds were characterized and compared with unsubstituted scaffold (B&#95;Sc). All of them contained well interconnected ultralarge pores (pores >400 μm) ideal for vascular ingrowth and proliferation of cells. Macropores of size 100-400 μm were present inside the scaffolds. In addition, low-angle X-ray diffraction showed that B&#95;Sc and scaffolds with substituent contents up to 0.4% exhibited ordered mesoporosity useful for hosting molecules with biological activity. The textural properties of B&#95;Sc were a surface area of 398 m(2) g(-1), a pore diameter of 4.3 nm and a pore volume of 0.43 cm(3) g(-1). A slight decrease in surface area and pore volume was observed upon substitution with no distinct effect on pore diameter. In addition, all the MBG&#95;Scs except 2.0% ZnO&#95;Sc showed quite quick in vitro bioactive response. Hence, the present study is a positive addition to ongoing research into preparing bone tissue engineering scaffolds from bioceramics containing elements of therapeutic significance., (Copyright © 2012 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.)

The present study is aimed at investigating the contribution of two biologically important cations, Mg(2+) and Sr(2+), when substituted into the structure of hydroxyapatite (Ca(10)(PO(4))(6)(OH)(2),HA). The substituted samples were synthesized by an aqueous precipitation method that involved the addition of Mg(2+)- and Sr(2+)-containing precursors to partially replace Ca(2+) ions in the apatite structure. Eight substituted HA samples with different concentrations of single (only Mg(2+)) or combined (Mg(2+) and Sr(2+)) substitution of cations have been investigated and the results compared with those of pure HA. The obtained materials were characterized by X-ray powder diffraction, specific surface area and porosity measurements (N(2) adsorption at 77 K), FT-IR and Raman spectroscopies and scanning electron microscopy. The results indicate that the co-substitution gives rise to the formation of HA and β-TCP structure types, with a variation of their cell parameters and of the crystallinity degree of HA with varying levels of substitution. An evaluation of the amount of substituents allows us to design and prepare BCP composite materials with a desired HA/β-TCP ratio.

A series of Ga-containing phospho-silicate glasses based on Bioglass 45S5, having molar formula 46.2SiO2·24.3Na2O·26.9CaO·2.6P2O5·xGa2O3 (x=1.0, 1.6, 3.5), were prepared by fusion method. The reference Bioglass 45S5 without gallium was also prepared. The synthesized glasses were immersed in simulated body fluid (SBF) for 30 days in order to observe ion release and hydroxyapatite (HA) formation. All Ga-containing glasses maintain the ability of HA formation as indicated by main X-ray diffractometric peaks and/or electronic scanning microscopy results. HA layer was formed after 1 day of SBF soaking in 45S5 glass containing up to 1.6% Ga2O3 content. Moreover, gallium released by the glasses was found to be partially precipitated on the glass surface as gallium phosphate. Further increase in gallium content reduced the ion release in SBF. The maximum of Ga(3+) concentration measured in solution is ~6 ppm determined for 3.5% Ga2O3 content. This amount is about half of the toxic level (14 ppm) of gallium and the glasses release gallium till 30 days of immersion in SBF. Considering the above results, the studied materials can be proposed as bioactive glasses with additional antimicrobial effect of gallium having no toxic outcome., (Copyright © 2012 Elsevier B.V. All rights reserved.)

Potentially bioactive fluorine-containing glasses of formula 46.2SiO(2)·24.3Na(2)O·(26.9-x)CaO·2.6P(2)O(5)·xCaF(2) [x = (0), 5, 10, 15] have been studied: the study was carried out as a function of fluorine percentage, dimensions and time of soaking in SBF. The results are compared to those obtained in the same conditions for Bioglass(®) 45S5. Due to the high number and different kind of variables/conditions explored by this set of data, the results are rationalized for the first time by means of multivariate data analysis (MDA); in this way it is possible to classify the behaviour of bioglasses toward bioactivity. The presence of fluorine does not inhibit the formation of HA; in particular, for a fast bioactivity (in term of HA crystallization) it will be better to have large particle size or slabs, while for a fast dissolution fine particle sizes should be preferred.

Some soda-lime-phospho-silicate glasses, such as Hench's Bioglass(®) 45S5, form bone-like apatite on their surface when bound to living bone. To improve their osteointegration for clinical purposes, the fluoride insertion in their structure has been proposed, but we recently showed that fluoride causes oxidative damage in human MG-63 osteoblasts, via inhibition of pentose phosphate oxidative pathway (PPP) and its key enzyme glucose 6-phosphate dehydrogenase (G6PD). In the same cells we have now investigated the role of nitric oxide (NO) in these effects. Fluoride-containing bioactive glasses and NaF caused, as expected, release of lactate dehydrogenase in the extracellular medium, accumulation of intracellular malonyldialdehyde, inhibition of PPP and G6PD: we have now observed that these effects were significantly reverted not only by superoxide dismutase (SOD) plus catalase (scavengers of reactive oxygen species), but also by N-monomethyl l-arginine (l-NMMA, a NOS inhibitor) and 2-phenyl-4,4,5,5,-tetramethylimidazoline-1oxyl 3-oxide (PTIO, a NO scavenger). Moreover the two highest concentrations of both fluoride-containing bioglasses and NaF caused increase of nitrite (a stable derivative of NO) levels in the culture supernatant, which was inhibited by l-NMMA, erythrocytes, PTIO and SOD/catalase, and increase of intracellular NO synthase (NOS) activity. The incubation with bioglasses or NaF increased also the phosphorylation of Ser(1177) in the endothelial NOS isoform. Furthermore, the NO donor spermine NONOate was able to inhibit G6PD activity in vitro, and this effect was partly reverted by PTIO. Therefore our results suggest that most cytotoxic effects of fluoride are mediated by the production of NO: reactive oxygen species are important, causing NOS phosphorylation. We also observed, for the first time, that Tempol, but not SOD/catalase, besides inhibiting the oxidative stress induced by fluoride, also scavenges fluoride ions. For this reason it is not a selective inhibitor of the oxidative effects of fluoride., (Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.)

It is demonstrated here that bioactive glasses containing Au nanoparticles (AuNPs) can be selectively functionalized with small molecules carrying either amino or thiol groups by simply varying the temperature and pH of the functionalization batch. The results evidence the following. (i) At room temperature (RT), no functionalization of Au-free glass occurs, whereas in the case of glasses containing AuNPs, stable linkages form only with amino groups, as in this condition Au does not bind with either thiol or hydroxyl groups. The RT functionalization with cysteine and cystine confirms the preferential functionalization through the amino groups, while the -SH groups are oxidized to S-S bridges. (ii) The functionalization with cysteine and cystine, compared at pH = 5, 9, and 12, is shown not to take place at pH = 5 and to be hindered by the glass matrix dissolution at pH = 12 (with consequent release of AuNPs), while the best results are obtained at pH = 9. (iii) For the effect of reaction temperature, at 4 °C it is possible to obtain a strong Au-S interaction, whereas at RT, a weak Au-N linkage is formed. These results should allow production, in a selective way, of different bonds exhibiting different strengths and, consequently, different release times in solution, with a wide range of possible applications (for instance, weak Au-N bonds in the case of drug delivery, strong Au-S bonds in protein immobilization).

Bioactive glasses containing gold nanoparticles (AuNPs) have been synthesized via the sol-gel route using HAuCl(4) x 3 H(2)O as gold precursor. The formation process of AuNPs was studied as a function of the thermal treatment, which induces nucleation of Au particles and influences their nature, optical properties, shape, size, and distribution. The physicochemical characterization indicates that the sample treated at 600 degrees C presents the best characteristics to be used as a bioactive material, namely high surface area, high amount of AuNPs located at the glass surface, presence of micropores, and abundant surface OH groups. In the case of samples either aged at 60 degrees C or calcined at 150 degrees C, AuNPs just begin their formation, and at this stage the gel is not completely polymerized and dried yet. A thermal treatment at higher temperatures (900 degrees C) causes the aggregation of AuNPs, forming "AuMPs" (i.e., Au microparticles) in a densified glass-ceramic material with low surface area, absence of pores, and low number of surface OH groups. These features induce in the glass-ceramic materials treated at high-temperatures a lower bioactivity (evidenced by SBF reaction), as compared with that exhibited by the glass samples treated at 600 degrees C.

Bioactive glasses such as Hench's 45S5 (Bioglass) have applications to tissue engineering as well as bone repair, and the insertion of fluoride in their composition has been proposed to enhance their bioactivity. In view of a potential clinical application, we investigated whether fluoride-containing glasses exert toxic effects on human MG-63 osteoblasts, and whether and how fluoride, which is released in the cell culture medium, might play a role in such cytotoxicity. A 24h incubation with 50 microg/ml (12.5 microg/cm(2)) of fluoride-containing bioactive glasses termed HCaCaF(2) (F content: 5, 10 and 15 mol.%) caused the release of lactate dehydrogenase in the extracellular medium (index of cytotoxicity), the accumulation of intracellular malonyldialdehyde (index of lipoperoxidation), and the increase of glutathione consumption. Furthermore, fluoride-containing glasses inhibited the pentose phosphate oxidative pathway and the glucose 6-phosphate dehydrogenase activity. These effects are ascribable to the fluoride content/release of glass powders, since they were mimicked by NaF solutions and were prevented by dimethyl sulfoxide and tempol (two radical scavengers), by superoxide dismutase (a superoxide scavenger), and by glutathione (the most important intracellular antioxidant molecule), but not by apocynin (an inhibitor of NADPH oxidase). The presence of fluoride-containing glasses and NaF caused also the generation of reactive oxygen species, which was prevented by superoxide dismutase and catalase. The data suggest that fluoride released from glasses is the cause of MG-63 cell oxidative damage and is independent of NADPH oxidase activation. Our data provide a new mechanism to explain F(-) ions toxicity: fluoride could trigger, at least in part, an oxidative stress via inhibition of the pentose phosphate oxidative pathway and, in particular, through the oxidative inhibition of glucose 6-phosphate dehydrogenase., (Copyright (c) 2009 Elsevier Ireland Ltd. All rights reserved.)

The aim of this work was to study the behaviour of zinc-doped phosphosilicate glasses based on Bioglass 45S5. In vitro (in simulated body fluid), the reactivity was analysed by means of inductively coupled plasma spectrometry, environmental scanning electron microscopy-energy-dispersive spectroscopy (ESEM-EDS) and X-ray diffraction. In vivo (a rat implanted with glass), the reactivity and the tissue behaviour were analysed by conventional histology, histochemistry, microradiography and ESEM-EDS. The in vivo behaviour matches that in vitro perfectly; they show comparable glass degradation processes and rates, ruled by the amount of zinc in the glass. The reaction mechanism for the formation of a polymerized silica layer superimposed with a peripheral calcium phosphate layer is clearly substantiated by ESEM-EDS investigations. The crystallization of a biologically active hydroxyapatite (HA) layer is observed in both cases; the in vitro experiment shows the presence of HA after 4 days.

The crystallization kinetics of Na(2)O.CaO.2SiO(2) (x = 0) and 0.68ZnO.Na(2)O.CaO.2SiO(2) (x = 0.68, where x is the ZnO stoichiometric coefficient in the glass formula) bioactive glasses have been studied using both nonisothermal and isothermal methods. The results obtained from isothermal XRPD analyses have showed that the first glass crystallizes into the isochemical Na(2)CaSi(2)O(6) phase, whereas the Na(2)ZnSiO(4) crystalline phase is obtained from the Zn-rich glass, in addition to Na(2)CaSi(2)O(6). The activation energy (Ea) for the crystallization of the Na(2)O.CaO.2SiO(2) glass is 193 +/- 10 and 203 +/- 5 kJ/mol from the isothermal in situ XRPD and nonisothermal DSC experiments, respectively. The Avrami exponent n determined from the isothermal method is 1 at low temperature (530 degrees C), and its value increases linearly with temperature increase up to 2 at 607 degrees C. For the crystallization of Na(2)CaSi(2)O(6) from the Zn-containing glass, higher values of both the crystallization temperature (667 and 661 degrees C) and Ea (223 +/- 10 and 211 +/- 5 kJ/mol) have been found from the isothermal and nonisothermal methods, respectively. The Na(2)ZnSiO(4) crystalline phase crystallizes at lower temperature with respect to Na(2)CaSi(2)O(6), and the Ea value is 266 +/- 20 and 245 +/- 15 kJ/mol from the isothermal and nonisothermal methods, respectively. The results of this work show that the addition of Zn favors the crystallization from the glass at lower temperature with respect to the Zn-free glass. In fact, it causes an increase of Ea for the Na diffusion process, determined using MD simulations, and consequently an overall increase of Ea for the crystallization process of Na(2)CaSi(2)O(6). Our results show good agreement between the Ea and n values obtained with the two different methods and confirm the reliability of the nonisothermal method applied to kinetic crystallization of glassy systems. This study allows the determination of the temperature stability field of the crystalline phases with the view of creating a different glass ceramic useful in the field of bioactive materials.

Bioactive glasses such as Hench's 45S5 have applications to tissue engineering and bone repair: the insertion of zinc has been proposed to improve their bone-bonding ability and to slacken their dissolution in extracellular body fluids. In view of a potential clinical application, we have investigated whether zinc-containing 45S5 (HZ) glasses might be cytotoxic for human MG-63 osteoblasts. In our experimental conditions, after 24h of incubation HZ glasses released significant amounts of Zn(2+) and induced in MG-63 cells release of lactate dehydrogenase (index of cytotoxicity) and the following indexes of oxidative stress: (i) accumulation of intracellular malonyldialdehyde, (ii) increased activity of pentose phosphate pathway, (iii) increased expression of heme oxygenase-1, (iv) increased activity of Cu,Zn-superoxide dismutase, (v) decreased level of intracellular thiols. These effects were inversely related to the zinc content of glass powders, were mimicked by ZnCl(2) solutions and were prevented by either metal chelators (EDTA, NTA) or the antioxidant ascorbate, suggesting that Zn(2+) released fastly from HZ glasses can cause MG-63 cell damage via an oxidative stress. This work highlights the importance of designing Zn-containing bioactive glasses without cytotoxic effects and gives supplementary information about the prooxidant role of zinc in living systems.

A new empirical pairwise potential model for ionic and semi-ionic oxides has been developed. Its transferability and reliability have been demonstrated by testing the potentials toward the prediction of structural and mechanical properties of a wide range of silicates of technological and geological importance. The partial ionic charge model with a Morse function is used, and it allows the modeling of the quenching of melts, silicate glasses, and inorganic crystals at high-pressure and high-temperature conditions. The results obtained by molecular dynamics and free energy calculations are discussed in relation to the prediction of structural and mechanical properties of a series of soda lime silicate glasses.

The adsorption of hexametaphosphate ion, an important deflocculant used in the ceramic industry, from aqueous solutions onto kaolinite has been studied at different temperatures. The adsorption isotherm follows the Langmuir model: the thermodynamic parameters DeltaG(ads)(0), DeltaH(ads)(0), and DeltaS(ads)(0) were calculated and found to be consistent with an interaction model involving the formation of an inner-sphere complex between HMP and aluminol groups. Also, the dependence of the adsorption behavior on the kaolinite volume fraction has been studied and discussed in term of association processes between the clay particles.

An automatic tool (named CLUSTER) for the prediction of the most probable crystal phases that can separate from glasses has been developed. The program analyzes the output of molecular dynamics simulations of glasses or glass ceramics, systematically sampling the ratios of the ions in different portions of the simulation box and comparing them to the stoichiometric ratio of compositionally equivalent crystalline phases retrieved from a crystal structure database. The efficacy of the similarity index elaborated has been judged by comparing the results obtained with the crystal phases identified by XRD analysis after thermal treatment in a series of multicomponent potential bioactive glasses and glass ceramics for which the advantages of rational-designed erosion-controlled release is straightforward.

The results of a qualitative and quantitative structure-property relationships analysis of multicomponent potential bioglasses of composition (2 - y) SiO2 x 1 Na2O x 1.1 CaO x y P2O5 x x ZnO (x = 0, 0.16, 0.35, 0.78 and y = 0.10, 0.20, 0.36) are presented. Quantitative models are obtained by means of structural descriptors derived by molecular dynamics simulations and experimental data measured for density, thermal analysis, 29Si and 31P magic angle spinning NMR, and chemical durability in water. Analysis of the crystal species obtained upon glass crystallization helped in the rationalization of the structural role of the different components. Finally, glass surface characterization with scanning electron microscopy, transmission electron microscopy, and X-ray diffraction after soaking in acellular simulated body fluid demonstrated the in vitro bioactivity of the newly obtained 1.80 SiO2 x 1 Na2O x 1.1 Ca x 0.20 P2O5 x 0.16 ZnO (HP5Z5) glass, corresponding to x = 0.16 and y = 0.20.

The reaction behaviour of synthetic hydroxyapatite [Ca10(PO4)6(OH)2] (HAP) toward cadmium ion was investigated for the Cd/Ca molar ratio in the range 1-0.005, by means of ions, pH measurements and XRD, SEM, IR techniques. The reaction behaviour between HAP and cadmium ion could be explained by a formation of an amorphous phase and/or a sorption mechanism.