Sol-Gel Synthesis of Phosphate-Based Glasses for Biomedical Applications

This thesis concerns the development of a new and facile sol-gel synthesis route for production of phosphate-based glasses for biomedical applications including; tissue engineering, imaging contrast agents and drug delivery systems. The structure of the prepared samples was probed by XRD, 31P MAS-NMR, EDX and FTIR spectroscopy that confirmed successful synthesis and production of phosphate based glasses via the sol-gel method. In this study, for the first time, quaternary phosphate-based sol-gel derived glasses in the P2O5–CaO–Na2O–TiO2 system with a high TiO2 content of up to 30 mol% were synthesised. While incorporating a high percentage of titanium into the phosphate network is non-trivial via traditional melt quench methods. Investigation of quaternary glasses with the general formula of (P2O5)55–(CaO)25–(Na2O)(20-x)–(TiO2)x, where X = 0, 5, 10 or 15 revealed, substituting titanium in place of sodium significantly improves the stability and prolongs the degradation of these glasses, which opens up a number of potential biomedical applications. Cell studies on titanium-stabilised glasses suggested glasses containing 5 or 10 mol% TiO2 have optimal potential for bone tissue engineering applications. Electrospraying was used to prepare (P2O5)55–(CaO)30– (Na2O)15 glass nanospheres with a diameter size range of 200-500 nm. These glass nano spheres were used as a transient contrast agent for ultrasound imaging to label mesenchymal stem cells and it was determined in vitro and in vivo that these nanospheres had a detection limit of 5 and 9 μg.mL-1, respectively. Cell counts down to 4000 could be measured with ultrasound imaging with no cytotoxicity at doses required for imaging. Glass nanospheres were also used as a carrier for drug delivery applications with a linear release of tetracycline hydrochloride molecules within the first 4 hours of the study period. Importantly, ion release studies confirmed these glass nanospheres biodegrade into an aqueous medium with degradation products that can be easily metabolised in the body. To the knowledge of the author, this is the first report of sol-gel synthesis and electrospraying to prepare glass nanospheres at low processing temperature and the first use of such a system for both diagnostic and therapeutic purposes

Novel sol–gel preparation of (PO)–(CaO)–(NaO)–(TiO) bioresorbable glasses (X = 0.05, 0.1, and 0.15)

Quaternary phosphate-based glasses in the PO–CaO–NaO–TiO system with a fixed PO and CaO content of 40 and 25 mol% respectively have been successfully synthesised via sol–gel method and bulk, transparent samples were obtained. The structure, elemental proportion, and thermal properties of stabilised sol–gel glasses have been characterised using X-ray diffraction (XRD), energy dispersive X-ray spectroscopy (EDX), P nuclear magnetic resonance (P NMR), titanium K-edge X-ray absorption near-edge structure (XANES), fourier transform infrared (FTIR) spectroscopy, and differential thermal analysis (DTA). The XRD results confirmed the amorphous nature for all stabilized sol–gel derived glasses. The EDX result shows the relatively low loss of phosphorus during the sol–gel process and Ti K-edge XANES confirmed titanium in the glass structure is in mainly six-fold coordination environment. The P NMR and FTIR results revealed that the glass structure consist of mainly Q and Q phosphate units and the Ti cation was acting as a cross-linking between phosphate units. In addition DTA results confirmed a decrease in the glass transition and crystallisation temperature with increasing NaO content. Ion release studies also demonstrated a decrease in degradation rates with increasing TiO content therefore supporting the use of these glasses for biomedical applications that require a degree of control over glass degradation. These sol–gel glasses also offer the potential to incorporate proactive molecules for drug delivery application due to the low synthesis temperature employed

Mesoporous Strontium-Doped Phosphate-Based Sol-Gel Glasses for Biomedical Applications

Mesoporous phosphate-based glasses have great potential as biomedical materials being able to simultaneously induce tissue regeneration and controlled release of therapeutic molecules. In the present study, a series of mesoporous phosphate-based glasses in the P2O5-CaO-Na2O system doped with 1, 3, and 5 mol % of Sr2+ were prepared using the sol-gel method combined with supramolecular templating. A sample without strontium addition was prepared for comparison. The non-ionic triblock copolymer EO20PO70EO20 (P123) was used as a templating agent. SEM images revealed that all synthesized glasses have an extended porous structure. This was confirmed by N2 adsorption-desorption analysis at 77 K that shows a porosity typical of mesoporous materials. 31P magic angle spinning nuclear magnetic resonance (31P MAS-NMR) and Fourier transform infrared (FTIR) spectroscopies have shown that the glasses are mainly formed by Q1 and Q2 phosphate groups. Degradation of the glasses in deionized water assessed over a 7-day period shows that phosphate, Ca2+, Na+ and Sr2+ ions can be released in a controlled matter over time. In particular, a direct correlation between strontium content and degradation rate was observed. This study shows that Sr-doped mesoporous phosphate-based glasses have great potential in bone tissue regeneration as materials for controlled delivery of therapeutic ions

Sol-gel based materials for biomedical applications

Sol-gel chemistry offers a flexible approach to obtaining a diverse range of materials. It allows differing chemistries to be achieved as well as offering the ability to produce a wide range of nano-/micro-structures. The paper commences with a generalized description of the various sol-gel methods available and how these chemistries control the bulk properties of the end products. Following this, a more detailed description of the biomedical areas where sol-gel materials have been explored and found to hold significant potential. One of the interesting fields that has been developed recently relates to hybrid materials that utilize sol-gel chemistry to achieve unusual composite properties. Another intriguing feature of sol-gels is the unusual morphologies that are achievable at the micro- and nano-scale. Subsequently the ability to control pore chemistry at a number of different length scales and geometries has proven to be a fruitful area of exploitation, that provides excellent bioactivity and attracts cellular responses as well as enables the entrapment of biologically active molecules and their controllable release for therapeutic action. The approaches of fine-tuning surface chemistry and the combination with other nanomaterials have also enabled targeting of specific cell and tissue types for drug delivery with imaging capacity

Mesoporous Phosphate-Based Glasses Prepared via Sol-Gel

In the present study, a mesoporous phosphate-based glass (MPG) in the P2O5-CaO-Na2O system was synthesised, for the first time, using a combination of sol-gel chemistry and supramolecular templating. A comparison between the structural properties, bioactivity and biocompatibility of the MPG with a non-porous phosphate-based glass (PG) of analogous composition prepared via the same sol-gel synthesis method, but in the absence of a templating surfactant is also presented. Results indicate that the MPG has enhanced bioactivity and biocompatibility compared to the PG, despite having similar local structure and dissolution properties. In contrast to the PG, the MPG shows formation of hydroxyl carbonate apatite (HCA) on its surface after 24 hours of immersion in simulated body fluid. Moreover, MPG shows enhanced viability of Saos-2 osteosarcoma cells after 7 days of culturing. This suggests that textural properties (porosity and surface area) play a crucial role in the kinetics of HCA formation and in interaction with cells. Increased efficiency of drug loading and release over non-porous PG systems was proved using the antimicrobial tetracycline hydrochloride as a drug model. This study represents a significant advance in the field of mesoporous materials for drug delivery and bone tissue regeneration as it reports, for the first time, the synthesis, structural characterisation and biocompatibility of mesoporous calcium phosphate glasses.In the present study, a mesoporous phosphate-based glass (MPG) in the P2O5-CaO-Na2O system was synthesised, for the first time, using a combination of sol-gel chemistry and supramolecular templating. A comparison between the structural properties, bioactivity and biocompatibility of the MPG with a non-porous phosphate-based glass (PG) of analogous composition prepared via the same sol-gel synthesis method, but in the absence of a templating surfactant is also presented. Results indicate that the MPG has enhanced bioactivity and biocompatibility compared to the PG, despite having similar local structure and dissolution properties. In contrast to the PG, the MPG shows formation of hydroxyl carbonate apatite (HCA) on its surface after 24 hours of immersion in simulated body fluid. Moreover, MPG shows enhanced viability of Saos-2 osteosarcoma cells after 7 days of culturing. This suggests that textural properties (porosity and surface area) play a crucial role in the kinetics of HCA formation and in interaction with cells. Increased efficiency of drug loading and release over non-porous PG systems was proved using the antimicrobial tetracycline hydrochloride as a drug model. This study represents a significant advance in the field of mesoporous materials for drug delivery and bone tissue regeneration as it reports, for the first time, the synthesis, structural characterisation and biocompatibility of mesoporous calcium phosphate glasses

Hierarchy of piecewise non-linear maps with non-ergodicity behavior

We study the dynamics of hierarchy of piecewise maps generated by one-parameter families of trigonometric chaotic maps and one-parameter families of elliptic chaotic maps of $\mathbf{cn}$ and $\mathbf{sn}$ types, in detail. We calculate the Lyapunov exponent and Kolmogorov-Sinai entropy of the these maps with respect to control parameter. Non-ergodicity of these piecewise maps is proven analytically and investigated numerically . The invariant measure of these maps which are not equal to one or zero, appears to be characteristic of non-ergodicity behavior. A quantity of interest is the Kolmogorov-Sinai entropy, where for these maps are smaller than the sum of positive Lyapunov exponents and it confirms the non-ergodicity of the maps.Comment: 18 pages, 8 figure

Atomic-Scale Structural Characterization of Silver-Doped Phosphate-Based Glasses Prepared by Coacervation

Phosphate-based glasses (PBGs) are traditionally prepared using the high temperature melt quenching route (MQ) or via the more recent sol-gel method (SG) that requires the use of organic solvents. The coacervation method represents an excellent inexpensive and green alternative to MQ and SG, being performed in aqueous solution and at room temperature. Coacervation is particularly applicable for the production of PBGs designed for biomedical applications, because it allows for the inclusion of temperature sensitive molecules and it does not require the use of toxic solvents. Whereas the atomic structure of the melt quenched and sol-gel PBGs is known, the atomic structure of those prepared via coacervation has yet to be investigated. In this study, a comprehensive advanced structural characterization has been performed on phosphate-based glasses in the system P2O5–CaO–Na2O–Ag2O (Ag2O mol% = 0, 1, 3, 5, 9 and 14) prepared via the coacervation method. Glasses within this system should find application as bioresorbable biomaterials thanks to their ability to release bioactive ions in a controlled manner. In particular, they possess antibacterial properties, inferred by the release of Ag+ over time. High energy X-ray diffraction (HEXRD), 31P and 23Na solid state magic angle spinning nuclear magnetic resonance (MAS NMR) and X-ray Absorption (XAS) at the Ag K-edge were used to probe the atomic structure of the glasses after drying in vacuum and after calcination at 300 °C. The length of the polyphosphate chains in the solid state appears to be independent of silver concentration, however, significant degradation of these chains is seen after calcination at 300 °C. Atomic-scale structure results indicate that the structure of these glasses is akin to that of other silver doped phosphate glasses prepared using the MQ and SG method. This suggests that phosphate-based glasses prepared using milder and greener conditions may have similar chemical and physical properties such as solubility, biocompatibility, and antibacterial properties

Strontium- and calcium-containing, titanium-stabilised phosphate-based glasses with prolonged degradation for orthopaedic tissue engineering.

Strontium- and calcium-releasing, titanium-stabilised phosphate-based glasses with a controlled degradation rate are currently under development for orthopaedic tissue engineering applications. Ca and/or Sr were incorporated at varying concentrations in quaternary phosphate-based glasses, in order to promote osteoinduction. Ti was incorporated at a fixed concentration in order to prolong degradation. Glasses of the general formula (P2O5)-(Na2O)-(TiO2)-(CaO)-(SrO) were prepared via the melt-quench technique. The materials were characterised by energy-dispersive X-ray spectroscopy, X-ray diffraction, (31)P magic angle spinning nuclear magnetic resonance, Fourier transform infrared spectroscopy, differential thermal analysis and density determination. The dissolution rate in distilled water was determined by measuring mass loss, ion release and pH change over a two-week period. In addition, the cytocompatibility and alkaline phosphatase activity of an osteoblast-like cell line cultured on the surface of glass discs was assessed. The glasses were shown to be amorphous and contained Q(1), Q(2) and Q(3) species. Fourier transform infrared spectroscopy revealed small changes in the glass structure as Ca was substituted with Sr and differential thermal analysis confirmed a decrease in crystallisation temperature with increasing Sr content. Degradation and ion release studies also showed that mass loss was positively correlated with Sr content. These results were attributed to the lower electronegativity of Sr in comparison to Ca favouring the formation of phosphate-based mineral phases. All compositions supported cell proliferation and survival and induced at least 2.3-fold alkaline phosphatase activity relative to the control. Glass containing 17.5 mol% Sr had 3.6-fold greater alkaline phosphatase activity than the control. The gradual release of Ca and Sr supported osteoinduction, indicating their potential suitability in orthopaedic tissue engineering applications

Waste sludge from shipping docks as a catalyst to remove amoxicillin in water with hydrogen peroxide and ultrasound

The waste sludge from shipping docks contains important elements that can be used as a catalyst after proper processing. The purpose of this study was to remove of amoxicillin (AMX) from the aquatic environment using waste sludge from shipping docks as catalyst in the presence of hydrogen peroxide/ultrasound waves. The catalyst was produced by treating waste sludge at 400 °C for 2 h. N2 adsorption, SEM, XRD, XRF, and FTIR techniques characterized the structural and physical properties of the catalyst. The BET-specific surface area of the catalyst reduced after AMX removal from 4.4 m2/g to 3.6 m2/g. To determine the optimal removal conditions, the parameters of the design of experiments were pH (5–9), contaminant concentration (5–100 mg/L), catalyst dosage (0.5–6 g/L), and concentration of hydrogen peroxide (10–100 mM). The maximum removal of AMX (98%) was obtained in the catalyst/hydrogen peroxide/ultrasound system at pH 5, catalyst dose of 4.5 g/L, H2O2 concentration of 50 mM, AMX concentration of 5 mg/L, and contact time of 60 min. The kinetics of removal of AMX from urine (k = 0.026 1/min), hospital wastewater (k = 0.021 1/min), and distilled water (k = 0.067 1/min) followed a first-order kinetic model (R2>0.91). The catalyst was reused up to 8 times and the AMX removal decreased to 45% in the last use. The byproducts and reaction pathway of AMX degradation were also investigated. The results clearly show that to achieve high pollutant removal rate the H2O2/ultrasound and catalyst/ultrasound synergy plays a key role

Customized clinical practice guidelines for management of adult cataract in Iran

Purpose: To customize clinical practice guidelines (CPGs) for cataract management in the Iranian population. Methods: First, four CPGs (American Academy of Ophthalmology 2006 and 2011, Royal College of Ophthalmologists 2010, and Canadian Ophthalmological Society 2008) were selected from a number of available CPGs in the literature for cataract management. All recommendations of these guidelines, together with their references, were studied. Each recommendation was summarized in 4 tables. The first table showed the recommendation itself in clinical question components format along with its level of evidence. The second table contained structured abstracts of supporting articles related to the clinical question with their levels of evidence. The third table included the customized recommendation of the internal group respecting its clinical advantage, cost, and complications. In the fourth table, the internal group their recommendations from 1 to 9 based on the customizing capability of the recommendation (applicability, acceptability, external validity). Finally, customized recommendations were sent one month prior to a consensus session to faculty members of all universities across the country asking for their comments on recommendations. Results: The agreed recommendations were accepted as conclusive while those with no agreement were discussed at the consensus session. Finally, all customized recommendations were codified as 80 recommendations along with their sources and levels of evidence for the Iranian population. Conclusion: Customization of CPGs for management of adult cataract for the Iranian population seems to be useful for standardization of referral, diagnosis and treatment of patients. © 2015 Journal of Ophthalmic and Vision Research | Published by Wolters Kluwer - Medknow