Ea Abou Neel

Controlled delivery of antimicrobial gallium ions from phosphate-based glasses

Gallium-doped phosphate-based glasses (PBGs) have been recently shown to have antibacterial activity. However, the delivery of gallium ions from these glasses can be improved by altering the calcium ion concentration to control the degradation rate of the glasses. In the present study, the effect of increasing calcium content in novel gallium (Ga2O3)-doped PBGs on the susceptibility of Pseudomonas aeruginosa is examined. The lack of new antibiotics in development makes gallium-doped PBG potentially a highly promising new therapeutic agent. The results show that an increase in calcium content (14, 15 and 16 mol.% CaO) cause a decrease in degradation rate (17.6, 13.5 and 7.3 microg mm(-2) h(-1)), gallium ion release and antimicrobial activity against planktonic P. aeruginosa. The most potent glass composition (containing 14 mol.% CaO) was then evaluated for its ability to prevent the growth of biofilms of P. aeruginosa. Gallium release was found to reduce biofilm growth of P. aeruginosa with a maximum effect (0.86 log(10) CFU reduction compared to Ga2O3-free glasses) after 48 h. Analysis of the biofilms by confocal microscopy confirmed the anti-biofilm effect of these glasses as it showed both viable and non-viable bacteria on the glass surface. Results of the solubility and ion release studies show that this glass system is suitable for controlled delivery of Ga3+. 71Ga NMR and Ga K-edge XANES measurements indicate that the gallium is octahedrally coordinated by oxygen atoms in all samples. The results presented here suggest that PBGs may be useful in controlled drug delivery applications, to deliver gallium ions in order to prevent infections due to P. aeruginosa biofilms.

Retention of mechanical properties and cytocompatibility of a phosphate-based glass fiber/polylactic acid composite

Polymers prepared from polylactic acid (PLA) have found a multitude of uses as medical devices. The main advantage of having a material that degrades is so that an implant would not necessitate a second surgical event for removal. In addition, the biodegradation may offer other advantages. In this study, fibers produced from a quaternary phosphate-based glass (PBG) in the system 50P(2)O(5)-40CaO-5Na(2)O-5Fe(2)O(3) (nontreated and heat-treated) were used to reinforce the biodegradable polymer, PLA. Fiber properties were investigated, along with the mechanical and degradation properties and cytocompatibility of the composites produced. Retention of mechanical properties overtime was also evaluated. The mean fiber strength for the phosphate glass fibers was 456 MPa with a modulus value of 51.5 GPa. Weibull analysis revealed a shape and scale parameter value of 3.37 and 508, respectively. The flexural strength of the composites matched that for cortical bone; however, the modulus values were lower than those required for cortical bone. After 6 weeks of degradation in deionized water, 50% of the strength values obtained was maintained. The composite degradation properties revealed a 14% mass loss for the nontreated and a 10% mass loss for the heat-treated fiber composites. It was also seen that by heat-treating the fibers, chemical and physical degradation occurred much slower. The pH profiles also revealed that nontreated fibers degraded quicker, thus correlating well with the degradation profiles. The in vitro cell culture experiments revealed both PLA (alone) and the heat-treated fiber composites maintained higher cell viability as compared to the nontreated fiber composites. This was attributed to the slower degradation release profiles of the heat-treated composites as compared to the nontreated fiber composites. SEM analyses revealed a porous structure after degradation, and it is clear that there are possibilities here to tailor the distribution of porosity within polymer matrices.

Surface preparation of bioactive Ni–Ti alloy using alkali, thermal treatments and spark oxidation

The primary aim of this study was to compare different surface treatments used for bioactivation of pure titanium surfaces––thermal, alkali treatment and spark oxidation, and to assess their suitability as treatments for Ni–Ti alloys. This was considered by examining the surface properties, calcium phosphate precipitation from a physiological solution, and nickel ion release. Additionally, changes in the transformation temperature were measured for thermally treated samples. These studies indicate that the native surface of Ni–Ti alloy is highly bioactive when assessing the precipitation of calcium phosphates from Hank’s solution. Low temperature heat treatments also produced promising surfaces while high temperature treatment resulted in a very low rate of Ca and P precipitation. Alkali treatment and spark oxidation resulted in some bioactivity. Nickel ion release was greatest for alkali treated and sparks oxidized samples, and the rate of its release from these two samples was on the verge of daily safe dose for adolescent human. The other analyzed samples revealed very low rates of nickel ion release. Heat treatment at 400°C resulted in significant increase in the transformation temperatures, and a further increase of the treatment temperature up to 600°C caused a drop of the transformation temperature.

Chemical, modulus and cell attachment studies of reactive calcium phosphate filler-containing fast photo-curing, surface-degrading, polymeric bone adhesives

The initial structure, setting and degradation processes of a poly(lactide-co-propylene glycol-co-lactide) dimethacrylate adhesive filled with 50, 60 or 70 wt.% reactive calcium phosphates (monocalcium phosphate monohydrate (MCPM)/beta-tricalcium phosphate (beta-TCP)) have been assessed using nuclear magnetic resonance, Fourier transform infrared spectroscopy, Raman, X-ray powder diffraction and gravimetric studies. Filler incorporation reduced the rapid light-activated monomer polymerization rates slightly, but not the final levels. Upon immersion in water for 24h, the set composite mass and volume increased due to water sorption. This promoted initial soluble MCPM loss from the composite surfaces, but also its reaction and monetite precipitation within the specimen bulk. After 48 h, composite gravimetric and chemical studies were consistent with surface erosion of polymer with reacted/remaining filler. The filled formulations exhibited more rapid early water sorption and subsequent surface erosion than the unfilled polymer. Calcium and phosphate release profiles and solution pH measurements confirmed early loss of surface MCPM with protons from polymer degradation products. At later times, the slower release of monetite/beta-TCP buffered composite storage solutions at approximately 5 instead of 3.2 for the unfilled polymer. Incorporation of filler increased both the early and later time material modulus. At intermediate times this effect was lost, presumably as a result of enhanced water sorption. The early modulus values obtained fell within the range reported for cancellous bone. Despite surface degradation, initial human mesenchymal cell attachment to both composites and polymer could be comparable with a non-degrading positive Thermanox control. These studies indicate that the filled formulations may be good candidates for bone repair. Release of calcium and phosphate ions provides components essential for such repair.

Phosphate-Based Glasses

This chapter reviews the development of phosphate-based glasses for biomedical use. Phosphate-based glasses are unique in that they are degradable and also their degradation rate can be controlled. The chapter commences with the basic concepts of glass structure that are pertinent to phosphate-based glasses and how the addition of other components affects glass structure at both the atomic and the bulk levels. In particular, an understanding of the role of bridging and nonbridging oxygens in the phosphate network, and their measurement by 31 P magic angle spinning nuclear magnetic resonance (MAS-NMR) will be addressed. The chapter goes on to describe the methods of synthesis, both conventional melt quenching and the more recently developed sol–gel derived synthesis routes. The conversion of these glasses to a fiber form is also discussed. The role of dopants in these glasses is clearly important and is highlighted in this chapter. The dopants can play two roles; they can either control the degradation rate and/or act as an active species that can either improve the bioactivity or act as an antibacterial ion. The chapter finishes with a section on the possible therapeutic uses, both in the medical and veterinary arenas.

Investigation of the Mixed Alkali Effect in a Range of Phosphate Glasses

This study investigated the mixed alkali effect in a series of phosphate based glasses. These glasses were of the composition 0.5P2O5-0.2CaO-0.3-xNa2O-xK2O where x=0 to 0.3 in steps of 0.05. This study considered density measurements using Archimedes’s principle, thermal characterisation using differential scanning calorimetry, phase analysis following crystallisation using X-ray powder diffraction (XRD), and degradation studies combined with ion release. The results showed that these mixed alkali glasses showed a linear decrease in density, with the ternary single alkali glass with 0.3mol K2O showing a 3% reduction in density as compared to that with 0.3mol Na2O which correlated well with the difference in ionic diameter and atomic weight of both cations. These glasses also showed intermediate glass transition temperature (Tg) values, compared to those of the ternary single alkali glasses having the same alkali oxide content, and the minimum Tg value was recorded for equimolar amounts of both alkali oxides. However, they did not show any significant change in the degradation rate compared to the glass with 0.3mol Na2O with the exception of the 0.25mol K2O glass. The single alkali glass with 0.3mol K2O showed a significant increase in the degradation rate by an approximate one order of magnitude. For the mixed alkali glasses with low molar concentration of K2O, only sodium phosphate-rich phases [NaCa(PO3)3 and Na4Ca(PO3)6] were detected from XRD; at high molar concentrations however, potassium phosphate-rich phases [KCa(PO3)3 and KPO3] were detected. At equimolar concentration of both alkali cations, KCa(PO3)3 and Na4Ca(PO3)6 were identified. K+, Ca2+, and P3O9 3- release followed the degradation behaviour where the highly degrading glasses with 0.25 and 0.3mol K2O released the highest amount of these ions; however, there was no definite trend in the remaining glass compositions.

Biocompatibility and other properties of phosphate-based glasses for medical applications

This chapter discusses phosphate-based glasses as biodegradable substitutes with a specific and controllable bioactivity. It starts with a general description of these glasses, highlighting the glass structure theories, formation, chemistry, terminology and properties. It also explores what these glasses can offer in terms of biomedical applications as bone tissue substitutes and antibacterial devices, with a particular focus placed on the in vitro and in vivo studies conducted on both monoliths and glass fibres. The application of these glasses as reinforcing agents for various composites is also considered. The chapter concludes with a discussion of the future of these glasses as biomaterials and highlights possible avenues of potential application.

1.18 Phosphate-Based Glasses

This chapter reviews the development of phosphate-based glasses for biomedical use. Phosphate-based glasses are unique in that they are degradable and also their degradation rate can be controlled. The chapter commences with the basic concepts of glass structure that are pertinent to phosphate-based glasses and how the addition of other components affects glass structure at both the atomic and the bulk levels. In particular, an understanding of the role of bridging and nonbridging oxygens in the phosphate network, and their measurement by 31 P magic angle spinning nuclear magnetic resonance (MAS-NMR) will be addressed. The chapter goes on to describe the methods of synthesis, both conventional melt quenching and the more recently developed sol–gel derived synthesis routes. The conversion of these glasses to a fiber form is also discussed. The role of dopants in these glasses is clearly important and is highlighted in this chapter. The dopants can play two roles; they can either control the degradation rate and/or act as an active species that can either improve the bioactivity or act as an antibacterial ion. The chapter finishes with a section on the possible therapeutic uses, both in the medical and veterinary arenas.

Antibacterial adhesives for bone and tooth repair

Bonding and repair of damaged tooth and bone directly in vivo is a more complicated problem than joining and assembly in the laboratory or factory. This is due to the requirement for the restorative material to be of low toxicity but capable of rapid set at body temperature and in the presence of bodily fluids and other tissues. Furthermore, bacteria and enzymes that penetrate the interface between adhesive materials and tissue can break down the latter and degrade any bond. In addition to having mechanical properties comparable with the tissue they replace, set formulations must preferably therefore be antibacterial and aid repair of damaged tissue. This chapter provides a general description of commercially available in vivo setting materials, cements and adhesives for tooth and bone repair and their current major drawbacks. It subsequently explores how these materials are being modified to reduce recurrent infections and encourage better surrounding tissue repair.