Controlling ion release from bioactive glass foam scaffolds with antibacterial properties.

Bioactive glass scaffolds have been produced, which meet many of the criteria for an ideal scaffold for bone tissue engineering applications, by foaming sol-gel derived bioactive glasses. The scaffolds have a hierarchical pore structure that is very similar to that of cancellous bone. The degradation products of bioactive glasses have been found to stimulate the genes in osteoblasts. This effect has been found to be dose dependent. The addition of silver ions to bioactive glasses has also been investigated to produce glasses with bactericidal properties. This paper discusses how changes in the hierarchical pore structure affect the dissolution of the glass and therefore its bioactivity and rate of ion delivery and demonstrates that silver containing bioactive glass foam scaffolds can be synthesised. It was found that the rate of release of Si and Ca ions was more rapid for pore structures with a larger modal pore diameter, although the effect of tailoring the textural porosity on the rate of ion release was more pronounced. Bioactive glass scaffolds, containing 2 mol% silver, released silver ions at a rate that was similar to that which has previously been found to be bactericidal but not high enough to be cytotoxic to bone cells.

The use of advanced diffraction methods in the study of the structure of a bioactive calcia: silica sol-gel glass.

Sol-gel derived calcium silicate glasses may be useful for the regeneration of damaged bone. The mechanism of bioactivity is as yet only partially understood but has been strongly linked to calcium dissolution from the glass matrix. In addition to the usual laboratory-based characterisation methods, we have used neutron diffraction with isotopic substitution to gain new insights into the nature of the atomic-scale calcium environment in bioactive sol-gel glasses, and have also used high energy X-ray total diffraction to probe the nature of the processes initiated when bioactive glass is immersed in vitro in simulated body fluid. The data obtained point to a complex calcium environment in which calcium is loosely bound within the glass network and may therefore be regarded as facile. Complex multi-stage dissolution and mineral growth phases were observed as a function of reaction time between 1 min and 30 days, leading eventually, via octacalcium phosphate, to the formation of a disordered hydroxyapatite (HA) layer on the glass surface. This methodology provides insight into the structure of key sites in these materials and key stages involved in their reactions, and thereby more generally into the behaviour of bone-regenerative materials that may facilitate improvements in tissue engineering applications.

Substrate chemistry influences the morphology and biological function of adsorbed extracellular matrix assemblies.

In addition to mediating cell signalling events, native extracellular matrix (ECM) assemblies interact with other ECM components, act as reservoirs for soluble signalling molecules and perform structural roles. The potential of native ECM assemblies in the manufacture of biomimetic materials has not been fully exploited due, in part, to the effects of substrate interactions on their morphology. We have previously demonstrated that the ECM components, fibrillin and type VI collagen microfibrils, exhibit substrate dependent morphologies on chemically and topographically variable heterogeneous surfaces. Using both cleaning and coating approaches on silicon wafers and glass coverslips we have produced chemically homogeneous, topographically similar substrates which cover a large amphiphilic range. Extremes of substrate amphiphilicity induced morphological changes in periodicity, curvature and lateral spreading which may mask binding sites or disrupt domain structure. Biological functionality, as assayed by the ability to support cell spreading, was significantly reduced for fibrillin microfibrils adsorbed on highly hydrophilic substrates (contact angle 20.7 degrees) compared with less hydrophilic (contact angle 38.3 degrees) and hydrophobic (contact angle 92.8 degrees) substrates. With an appropriate choice of surface chemistry, multifunctional ECM assemblies retain their native morphology and biological functionality.

Dose- and time-dependent effect of bioactive gel-glass ionic-dissolution products on human fetal osteoblast-specific gene expression.

Bioactive glasses dissolve upon immersion in culture medium, and release their constitutive ions into solution. There has been some evidence suggesting that these ionic-dissolution products influence osteoblast-specific processes. Here, the effect of 58S sol-gel-derived bioactive glass (60% SiO(2), 36% CaO, 4% P(2)O(5), in molar percentage) on primary osteoblasts derived from human fetal long bone explant cultures is investigated, and it is hypothesized that critical concentrations of sol-gel-dissolution products (consisting of a combination of simple inorganic ions) can enhance osteoblast phenotype in vitro by affecting the expression of a number of genes associated with the differentiation and extracellular matrix deposition processes. Cells were exposed to a range of 58S dosages continuously for a period of 4-14 days in monolayer cultures. Quantitative real-time RT-PCR analysis of a panel of osteoblast-specific markers showed a varied gene expression pattern in response to the material. The highest concentration of Ca and Si tested (96 and 50 ppm, respectively) promoted upregulation of gene expression for most markers (including alkaline phosphatase, osteocalcin, and osteopontin) at the latest time point, compared to non-58S-treated control, although this observation was not statistically significant. The same 58S concentration produced higher ALP activity levels and increased proliferation throughout the culture period, compared to lower dosages tested; however, the results generated were again not statistically significant. The data overall suggest that no significant effect can be ascribed to the ionic products of 58S bioactive gel-glass dissolution tested here and their ability to stimulate osteoblastic marker gene expression.

Binary CaO-SiO(2) gel-glasses for biomedical applications.

Bioactive materials are routinely used in dental and orthopaedic applications. The concept was first introduced in 1971, with the discovery of 45S5 Bioglass, which is known to develop an interfacial bond between the implant and the host tissue. This glass is composed of SiO(2), CaO, P(2)O(5) and Na(2)O. Since then numerous glasses and glass ceramics with similar compositions have been extensively studied for clinical applications. Until 1990 it was accepted that P(2)O(5) and Na(2)O were necessary components for the glass composition to be bioactive. However, calcium silicate glasses with high SiO(2) content are impossible to produce using the traditional melt-quench method. This is due to the liquid-liquid immiscibility region that is present between 0.02 and 0.3 mole fraction of CaO and in terms of bioactivity, high CaO compositions were inferior to those quaternary bioactive glass compositions already in existence. In the last few years several studies have been reported regarding the production of CaO-SiO(2) glasses via the sol-gel processing technique. This report summarises the findings of the past and the present and also outlines potential of these calcium silicate gel-glasses in the field of biomaterials.

Structural studies of bioactivity in sol-gel-derived glasses by X-ray spectroscopy.

Extended X-ray absorption fine structure spectroscopy and X-ray absorption near edge structure, X-ray fluorescence spectroscopy, and X-ray powder diffraction have been used to study the local calcium environment in four sol-gel-derived bioactive calcium silicate glasses of the general formula (CaO)(x)(SiO(2))(1-x). The formation of a hydroxyapatite layer on the composition with the highest bioactivity (x = 0.3) with time has been studied, in an in vitro environment, by immersion in simulated body fluid (SBF) at 37 degrees C. The calcium oxygen environment in the four compositions has been shown to be six-coordinate in character. Both the extended X-ray absorption fine structure spectroscopy and X-ray absorption near edge structure show a gradual increase in coordination number and Ca--O bond distance with longer exposure to SBF. X-ray fluorescence show that calcium is quickly lost from the samples on exposure to SBF and the calcium concentration then recovers with time. There is clear evidence that the recovery of calcium content is due to the formation of a CaO-P(2)O(5)-rich layer. Annealing of samples at 650 degrees C shows the presence of what, on the length scales probed by X-ray diffraction, appears to be noncrystalline calcium phosphate after 1 h of exposure to an SBF solution, which becomes more crystalline on longer exposure.

Bioactivity of gel-glass powders in the CaO-SiO2 system: a comparison with ternary (CaO-P2O5-SiO2) and quaternary glasses (SiO2-CaO-P2O5-Na2O).

Bioactive glasses react chemically with body fluids in a manner that is compatible with the repair processes of the tissues. This results in the formation of an interfacial bond between the glasses and living tissue. Bioactive glasses also stimulate bone-cell proliferation. This behavior is dependent on the chemical composition as well as the surface texture of the glasses. It has been recently reported that gel-derived monolith specimens in the binary SiO2 - CaO are bioactive over a similar molar range of SiO2 content as the previously studied ternary CaO-P2O5-SiO2 system. In this report, the preparation and bioactivity of the binary gel-glass powder with 70 mol % SiO2 is discussed and its bioactivity is compared with the melt-derived 45S5 (quaternary) Bioglass and sol-gel-derived 58S (ternary) bioactive gel-glass compositions. Dissolution kinetic parameters K(1) and K(2) were also computed based on the silicon release for all glass powders. It was shown that the simple two-component SiO2-CaO gel-glass powder is bioactive with comparable dissolution rates as the clinically used melt-derived 45S5 Bioglass powder and extensively studied sol-gel-derived 58S gel-glass powder.