Structural study of Al2O3-Na2O-CaO-P2O5 bioactive glasses as a function of aluminium content.

Calcium phosphate based biomaterials are extensively used in the context of tissue engineering: small changes in composition can lead to significant changes in properties allowing their use in a wide range of applications. Samples of composition (Al(2)O(3))(x)(Na(2)O)(0.11-x)(CaO)(0.445)(P(2)O(5))(0.445), where x = 0, 0.03, 0.05, and 0.08, were prepared by melt quenching. The atomic-scale structure has been studied using neutron diffraction and solid state (27)Al MAS NMR, and these data have been rationalised with the determined density of the final glass product. With increasing aluminium concentration the density increases initially, but beyond about 3 mol. % Al(2)O(3) the density starts to decrease. Neutron diffraction data show a concomitant change in the aluminium speciation, which is confirmed by (27)Al MAS NMR studies. The NMR data reveal that aluminium is present in 4, 5, and 6-fold coordination and that the relative concentrations of these environments change with increasing aluminium concentration. Materials containing aluminium in 6-fold coordination tend to have higher densities than analogous materials with the aluminium found in 4-fold coordination. Thus, the density changes may readily be explained in terms of an increase in the relative concentration of 4-coordinated aluminium at the expense of 6-fold aluminium as the Al(2)O(3) content is increased beyond 3 mol. %.

Do 'passive' medical titanium surfaces deteriorate in service in the absence of wear?

Globally, more than 1000 tonnes of titanium (Ti) is implanted into patients in the form of biomedical devices on an annual basis. Ti is perceived to be 'biocompatible' owing to the presence of a robust passive oxide film (approx. 4 nm thick) at the metal surface. However, surface deterioration can lead to the release of Ti ions, and particles can arise as the result of wear and/or corrosion processes. This surface deterioration can result in peri-implant inflammation, leading to the premature loss of the implanted device or the requirement for surgical revision. Soft tissues surrounding commercially pure cranial anchorage devices (bone-anchored hearing aid) were investigated using synchrotron X-ray micro-fluorescence spectroscopy and X-ray absorption near edge structure. Here, we present the first experimental evidence that minimal load-bearing Ti implants, which are not subjected to macroscopic wear processes, can release Ti debris into the surrounding soft tissue. As such debris has been shown to be pro-inflammatory, we propose that such distributions of Ti are likely to effect to the service life of the device.

Titanium-containing bioactive phosphate glasses.

The use of biomaterials has revolutionized the biomedical field and has received substantial attention in the last two decades. Among the various types of biomaterials, phosphate glasses have generated great interest on account of their remarkable bioactivity and favourable physical properties for various biomedical applications relating to both hard and soft tissue regeneration. This review paper focuses mainly on the development of titanium-containing phosphate-based glasses and presents an overview of the structural and physical properties. The effect of titanium incorporation on the glassy network is to introduce favourable properties. The biocompatibility of these glasses is described along with recent developments in processing methodologies, and the potential of Ti-containing phosphate-based glasses as a bone substitute material is explored.

Characterizing the hierarchical structures of bioactive sol-gel silicate glass and hybrid scaffolds for bone regeneration.

Bone is the second most widely transplanted tissue after blood. Synthetic alternatives are needed that can reduce the need for transplants and regenerate bone by acting as active temporary templates for bone growth. Bioactive glasses are one of the most promising bone replacement/regeneration materials because they bond to existing bone, are degradable and stimulate new bone growth by the action of their dissolution products on cells. Sol-gel-derived bioactive glasses can be foamed to produce interconnected macropores suitable for tissue ingrowth, particularly cell migration and vascularization and cell penetration. The scaffolds fulfil many of the criteria of an ideal synthetic bone graft, but are not suitable for all bone defect sites because they are brittle. One strategy for improving toughness of the scaffolds without losing their other beneficial properties is to synthesize inorganic/organic hybrids. These hybrids have polymers introduced into the sol-gel process so that the organic and inorganic components interact at the molecular level, providing control over mechanical properties and degradation rates. However, a full understanding of how each feature or property of the glass and hybrid scaffolds affects cellular response is needed to optimize the materials and ensure long-term success and clinical products. This review focuses on the techniques that have been developed for characterizing the hierarchical structures of sol-gel glasses and hybrids, from atomic-scale amorphous networks, through the covalent bonding between components in hybrids and nanoporosity, to quantifying open macroporous networks of the scaffolds. Methods for non-destructive in situ monitoring of degradation and bioactivity mechanisms of the materials are also included.

Bioactive glass scaffolds for bone regeneration and their hierarchical characterisation.

Scaffolds are needed that can act as temporary templates for bone regeneration and actively stimulate vascularized bone growth so that bone grafting is no longer necessary. To achieve this, the scaffold must have a suitable interconnected pore network and be made of an osteogenic material. Bioactive glass is an ideal material because it rapidly bonds to bone and degrades over time, releasing soluble silica and calcium ions that are thought to stimulate osteoprogenitor cells. Melt-derived bioactive glasses, such as the original Bioglass composition, are available commercially, but porous scaffolds have been difficult to produce because Bioglass and similar compositions crystallize on sintering. Sol-gel foam scaffolds have been developed that avoid this problem. They have a hierarchical pore structure comprising interconnected macropores, with interconnect diameters in excess of the 100 microm that is thought to be needed for vascularized bone ingrowth, and an inherent nanoporosity of interconnected mesopores (2-50 nm) which is beneficial for the attachment of osteoprogenitor cells. They also have a compressive strength in the range of cancellous bone. This paper describes the optimized sol-gel foaming process and illustrates the importance of optimizing the hierarchical structure from the atomic through nano, to the macro scale with respect to biological response.

Structural characterization by x-ray methods of novel antimicrobial gallium-doped phosphate-based glasses.

Antimicrobial gallium-doped phosphate-based glasses of general composition (P(2)O(5))(0.45)(CaO)(0.16)(Na(2)O)(0.39-x)(Ga(2)O(3))(x) (where x=0, 0.01, 0.03, and 0.05) have been studied using the advanced synchrotron-based techniques of Ga K-edge x-ray absorption spectroscopy and high-energy x-ray diffraction to provide a structural insight into their unique properties. The results show that the Ga(3+) ions are octahedrally coordinated. Furthermore, substitution of Na(2)O by Ga(2)O(3) strengthens the phosphate network structure because the presence of GaO(6) octahedra inhibits the migration of the remaining Na(+) ions. The results are discussed in terms of the use of Na(2)O-CaO-P(2)O(5) glasses as controlled-delivery devices for antimicrobial Ga(3+) ions in biomedical applications. We are thereby able to relate the atomic-scale environment of the Ga(3+) ions beneficially to the glass dissolution, and thus to their ability to disrupt bacterial cell activity by usurping the role of iron.

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.

Bioactive glass sol-gel foam scaffolds: Evolution of nanoporosity during processing and in situ monitoring of apatite layer formation using small- and wide-angle X-ray scattering.

Recent work has highlighted the potential of sol-gel-derived calcium silicate glasses for the regeneration or replacement of damaged bone tissue. The work presented herein provides new insight into the processing of bioactive calcia-silica sol-gel foams, and the reaction mechanisms associated with them when immersed in vitro in a simulated body fluid (SBF). Small-angle X-ray scattering and wide-angle X-ray scattering (diffraction) have been used to study the stabilization of these foams via heat treatment, with analogous in situ time-resolved data being gathered for a foam immersed in SBF. During thermal processing, pore sizes have been identified in the range of 16.5-62.0 nm and are only present once foams have been heated to 400 degrees C and above. Calcium nitrate crystallites were present until foams were heated to 600 degrees C; the crystallite size varied from 75 to 145 nm and increased in size with heat treatment up to 300 degrees C, then decreased in size down to 95 nm at 400 degrees C. The in situ time-resolved data show that the average pore diameter decreases as a function of immersion time in SBF, as calcium phosphates grow on the glass surfaces. Over the same time, Bragg peaks indicative of tricalcium phosphate were evident after only 1-h immersion time, and later, hydroxycarbonate apatite was also seen. The hydroxycarbonate apatite appears to have preferred orientation in the (h,k,0) direction.

A study of the formation of amorphous calcium phosphate and hydroxyapatite on melt quenched Bioglass using surface sensitive shallow angle X-ray diffraction.

Melt quenched silicate glasses containing calcium, phosphorous and alkali metals have the ability to promote bone regeneration and to fuse to living bone. These glasses, including 45S5 Bioglass((R)) [(CaO)(26.9)(Na(2)O)(24.4)(SiO(2))(46.1)(P(2)O(5))(2.6)], are routinely used as clinical implants. Consequently there have been numerous studies on the structure of these glasses using conventional diffraction techniques. These studies have provided important information on the atomic structure of Bioglass((R)) but are of course intrinsically limited in the sense that they probe the bulk material and cannot be as sensitive to thin layers of near-surface dissolution/growth. The present study therefore uses surface sensitive shallow angle X-ray diffraction to study the formation of amorphous calcium phosphate and hydroxyapatite on Bioglass((R)) samples, pre-reacted in simulated body fluid (SBF). Unreacted Bioglass((R)) is dominated by a broad amorphous feature around 2.2 A(-1) which is characteristic of sodium calcium silicate glass. After reacting Bioglass((R)) in SBF a second broad amorphous feature evolves ~1.6 A(-1) which is attributed to amorphous calcium phosphate. This feature is evident for samples after only 4 h reacting in SBF and by 8 h the amorphous feature becomes comparable in magnitude to the background signal of the bulk Bioglass((R)). Bragg peaks characteristic of hydroxyapatite form after 1-3 days of reacting in SBF.

The structure of calcium metaphosphate glass obtained from x-ray and neutron diffraction and reverse Monte Carlo modelling.

The short range structure of (CaO)(0.5)(P(2)O(5))(0.5) glass has been studied using x-ray and neutron diffraction and modelled using the reverse Monte Carlo method. Using this combination of techniques has allowed six interatomic correlations to be distinguished and fitted to obtain a set of bond lengths and coordination numbers that describe the structure of the glass. The glass consists of metaphosphate chains of phosphate tetrahedra and each phosphate unit has two non-bridging oxygen atoms available for coordination with Ca. The Ca-O correlation was fitted with two peaks at 2.35 and 2.86 Å, representing a broad distribution of bond lengths. The total Ca-O coordination is 6.9 and is consistent with distorted polyhedral units such as capped octahedra or capped trigonal prisms. It is found that most non-bridging oxygen atoms are bonded to two calcium atoms. All of these observations are consistent with Hoppe's model for phosphate glasses. Furthermore, the medium range order is revealed to consist of phosphate chains intertwined with apparently elongated clusters of Ca ions, and the Ca-O and Ca-P correlations contributed significantly to the first sharp diffraction peak in x-ray diffraction.

The atomic structure of niobium and tantalum containing borophosphate glasses.

A complete structural study has been carried out on sodium borophosphate glass containing increasing amounts of either niobium or tantalum. A combination of high energy x-ray diffraction, neutron diffraction, extended x-ray absorption fine structure, nuclear magnetic resonance, and infrared and Raman spectroscopy has been used to discern the local atomic structure of each component and the changes with M content, where M is either niobium or tantalum. The glasses are found to consist of tetrahedral borate and phosphate with octahedral MO(6). As expected, B and P play the roles of tetrahedral network formers. At low M content there are isolated MO(6) units with [Formula: see text] and [Formula: see text] linkages that contribute to the glass network. As the M content increases, the number of [Formula: see text] links increases, and at the highest M content each MO(6) unit is connected to several others. The octahedra become significantly distorted as the niobium content increases, an effect that is not seen for tantalum.

In situ high-energy X-ray diffraction study of a bioactive calcium silicate foam immersed in simulated body fluid.

The method of in situ time-resolved high-energy X-ray diffraction, using the intrinsically highly collimated X-ray beam generated by the European Synchrotron Radiation Facility, is demonstrated. A specially designed cell, which allows the addition of liquid components, has been used to study the reaction mechanisms of a foamed bioactive calcia-silica sol-gel glass immersed in simulated body fluid. Analysis of the X-ray diffraction data from this experiment provides atomic distances, via the pair correlation functions, at different stages of the dissolution of the glass and of the associated calcium phosphate, and ultimately hydroxyapatite, i.e. bone mineral, formation. Hence, changes in the atomic scale structure can be analysed as a function of reaction time, giving an insight into the evolution of the structure of both the glass matrix and the hydroxyapatite surface growth.

The structure of phosphate glass biomaterials from neutron diffraction and 31P nuclear magnetic resonance data.

Neutron diffraction and 31P nuclear magnetic resonance spectroscopy were used to probe the structure of phosphate glass biomaterials of general composition (CaO)0.5-x(Na2O)x(P2O5)0.5 (x = 0, 0.1 and 0.5). The results suggest that all three glasses have structures based on chains of Q2 phosphate groups. Clear structural differences are observed between the glasses containing Na2O and CaO. The P-O bonds to bridging and non-bridging oxygens are less well resolved in the neutron data from the samples containing CaO, suggesting a change in the nature of the bonding as the field strength of the cation increases [Formula: see text]. In the (CaO)0.5(P2O5)0.5 glass most of the Ca2+ ions are present in isolated CaOx polyhedra whereas in the (Na2O)0.5(P2O5)0.5 glass the NaOx polyhedra share edges leading to a Na-Na correlation. The results of the structural study are related to the properties of the (CaO)0.4(Na2O)0.1(P2O5)0.5 biomaterial.

A multinuclear solid state NMR study of the sol-gel formation of amorphous Nb2O5-SiO2 materials.

Multinuclear 1H, 13C, 17O, 29Si MAS and 93Nb static NMR is reported from a series of sol-gel prepared (Nb2O5)x(SiO2)(1-x) materials with x=0.03, 0.075 or 0.30. 13C NMR shows that by 500 degrees C the organic precursor fragments have been removed although some residual carbon remains as a separate phase. The 29Si NMR typically shows three Q-species (Q2,3,4) in the initial gels, and that with increasing heat treatment the average n of the Qn-species increases as the organic fragments and hydroxyl groups are removed. 17O shows unequivocally that the x=0.03 and 0.075 samples are not phase separated, while at the much higher niobia-content of x=0.30 Nb-O-Nb signals are readily detected, a definite indication of the atomic scale phase separation of Nb2O5. The x=0.03 and 0.075 samples heated to 750 degrees C are thus representative of amorphous niobium silicates. Comparison is made to other sol-gel prepared metal silicates especially with another Group Va metal tantalum. The effects of tantalum and niobium on the silica network are very different and it is suggested here that most of the niobium is present as NbO4, forming part of the silicate network.

The effects of different heat treatment and atmospheres on the NMR signal and structure of TiO2-ZrO2-SiO2 sol-gel materials.

The effects of different heat treatment schemes (i.e. successively or directly heated to particular temperatures) and atmospheres (air or nitrogen) on the solid-state NMR spectra obtained from (TiO(2))(0.15)(ZrO(2))(0.05)(SiO(2))(0.80) sol-gel materials are investigated. A combination of 1H, 13C, 17O and 29Si NMR is used. 29Si MAS NMR indicates that the extent of condensation of the silica-based network strongly depends on the maximum temperature the sample has experienced, but the condensation is largely independent of the details of the heat treatment scheme and atmosphere used. For sol-gel produced silicate-based materials the results show that the equilibrium structure at each temperature is reached rapidly compared to the time (2h) spent at that temperature. The 17O NMR results confirm that a nitrogen atmosphere does significantly reduce loss of 17O from the structure but care must be taken since there could be differential loss of 17O from the regions having different local structural characteristics.