Conjugation of amino-bioactive glasses with 5-aminofluorescein as probe molecule for the development of pH sensitive stimuli-responsive biomaterials

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.     

Aero‐Engine DCS Fault‐Tolerant Control with Markov Time Delay Based On Augmented Adaptive Sliding Mode Observer

With a focus on aero‐engine distributed control systems (DCSs) with Markov time delay, unknown input disturbance, and sensor and actuator simultaneous faults, a combined fault tolerant algorithm based on the adaptive sliding mode observer is studied. First, an uncertain augmented model of distributed control system is established under the condition of simultaneous sensor and actuator faults, which also considers the influence of the output disturbances. Second, an augmented adaptive sliding mode observer is designed and the linear matrix inequality (LMI) form stability condition of the combined closed‐loop system is deduced. Third, a robust sliding mode fault tolerant controller is designed based on fault estimation of the sliding mode observer, where the theory of predictive control is adopted to suppress the influence of random time delay on system stability. Simulation results indicate that the proposed sliding mode fault tolerant controller can be very effective despite the existence of faults and output disturbances, and is suitable for the simultaneous sensor and actuator faults condition.     

Reactivity of biological and synthetic hydroxyapatite towards Zn(II) ion, solid-liquid investigations

The reaction of biological and synthetic hydroxyapatite Ca₅(PO₄)₃OH (HAP) with Zn²⁺ ions is investigated as a function of Zn²⁺/Ca²⁺ molar ratio, time, temperature and electrolyte type (NaCl, NaHCO₃, Na₂HPO₄) by means of pH, pZn, pCa measurements, in aqueous solution. Biological powdered HAP invariably affords an almost quantitative reaction, while Zn²⁺ precipitated only partially by reaction with cubelets of biological HAP. Using powdered biological HAP and synthetic HAP (dried at 100 °C), the reaction with Zn²⁺ ion is fast and takes place without addition of precipitating anion; synthetic HAP (dried at 1000 °C) reacts if free phosphate ions are present. The solid phases separated after different reaction times are investigated by means of X-ray diffraction (XRD), IR, SEM techniques and elemental analysis (C,H,N). The solid phases contain Zn₃(PO₄)₂ { 4H₂O (Hopeite) at the beginning of reaction and CaZn₂(PO_{4 2} { 2H₂O (Scholzite) at the equilibrium.     

Role of the Surface Treatment in the Deflocculation of Kaolinite

Suspensions of untreated and properly treated Na-exchanged kaolinite have been subjected to rheological investigations using sodium hexametaphosphate (NaHMP) or sodium disilicate (DIS) as deflocculants. The treatment of the clay consisted of a 24 h contact with solutions of NaHMP or DIS and separation of the resulting solid phase. This was then used to form the suspensions subjected to the rheological measurements. The results indicate that the dispersion ability of each deflocculant is remarkably influenced by the type of treatment. In particular, with respect to the untreated kaolinite, the efficiency of DIS is dramatically increased when the clay has been previously treated with a NaHMP solution. On the other hand, a decrease in the dispersant ability of NaHMP is observed from the untreated kaolinite to the one previously treated with DIS.     

Cerium-doped bioactive 45S5 glasses: spectroscopic,redox, bioactivity and biocatalytic properties

The ability of Ce-containing bioactive glasses, based on 45S5 Bioglass^®, to inhibit oxidative stress in terms of reduction in hydrogen peroxide and superoxide (O₂ ^?), by mimicking the catalase and superoxide dismutase activity is reported in this work. The characterization is performed on the powders of pristine glasses and after the soaking in H₂O₂ solutions and simulated body fluid. The glass samples are analysed by XPS, XRD, UV–Vis and FT-IR. The best catalyst activities are obtained for the glass with the highest content of cerium (H_5.3 = 5.3 mol% of CeO₂ in the nominal glass composition), and the best Ce³⁺/Ce⁴⁺ ratio in terms of catalase mimetic activity is found to be a function of H₂O₂ concentration. Moreover, the detailed study of the surface during the mimic enzymatic activity tests shows the formation of a Ca-P-rich layer on the glass surface, where the presence of Ce ions favours the formation of CePO₄. The phosphate in turn inhibits the formation of hydroxyapatite, decreasing the bioactivity of the glass with the highest of CeO₂ in the glass composition. This work shows the effect of Ce³⁺/Ce⁴⁺ ratio towards the catalase mimetic activity and for the first time the superoxide dismutase mimetic activity of Ce-containing 45S5-derived glasses.     

Synthesis and characterization of bioactive glasses functionalized with Cu nanoparticles and organic molecules

Bioactive sol gel glasses, based on the ternary system 15CaO·5P₂O₅·80SiO₂, doped with Cu were synthesized and characterized in order to define the oxidation state of Cu as a function of thermal treatments. In particular, we were able to optimize the condition to obtain: (i) the reduction of Cu²⁺ to Cu⁰ followed by nano-aggregation of metal nano-particles (MeNPs) into glass matrix; (ii) a mixed Cu²⁺/Cu⁺/Cu⁰ NPs-containing glasses; (iii) a Cu²⁺-containing glasses.Successively, the surface of sol–gel glasses was functionalized by means of organic molecules (amino and mercapto alcohols) to give rise to a system that can interact with the functional groups of the drugs. The functionalization was carried out as a function of the sol–gel glass composition, organic molecules concentration and temperature of the process; the results indicate a preference for the amino groups. The bioactivity (formation of an apatitic layer after simulated body fluid SBF test) was verified for the functionalized sol–gel Cu²⁺-containing glasses and they are still bioactive.     

Gallium-containing phosphosilicate glasses: Functionalization and in-vitro bioactivity

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.     

Gallium-containing phospho‐silicate glasses: Synthesis and in vitro bioactivity

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 Ga³⁺ 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.