The antimicrobial efficacy of hypoxia mimicking cobalt oxide doped phosphate-based glasses against clinically relevant Gram positive, Gram negative bacteria and a fungal strain

Bioactive phosphate glasses are of considerable interest for a range of soft and hard tissue engineering applications. The glasses are degradable and can release biologically important ions in a controlled manner. The glasses can also potentially be used as an antimicrobial delivery system. In the given study, novel cobalt-doped phosphate-based glasses, (P 2O 5) 50(Na 2O) 20(CaO) 30-x(CoO) x where 0 ≤ x (mol %) ≤ 10, were manufactured and characterized. As the cobalt oxide concentration increased, the rate of dissolution was observed to decrease. The antimicrobial potential of the glasses was studied using direct and indirect contact methods against both Escherichia coli (NCTC 10538) Staphylococcus aureus (ATCC 6538) and Candida albicans (ATCC 76615). The results showed strong, time dependent, and strain specific antimicrobial activity of the glasses against microorganisms when in direct contact. Antimicrobial activity (R) ≥ 2 was observed within 2 h against Escherichia coli, whereas a similar effect was achieved in 6 h against Staphylococcus aureus and Candida albicans. However, when in indirect contact, the dissolution products from the bioactive glasses failed to show an antimicrobial effect. Following direct exposure to the glasses for 7 days, osteoblast-like SAOS-2 cells showed a 5-fold increase in VEGF mRNA while THP-1 monocytic cells showed a 4-fold increase in VEGF mRNA expression when exposed to 10% CoO-doped glass compared with the cobalt free control glass. Endothelial cells stimulated with conditioned medium taken from cell cultures of THP-1 monocytes exposed to 10% CoO doped glass showed clear tubelike structure (blood vessel) formation after 4 h

Atomic structure of Mg-based metallic glasses from molecular dynamics and neutron diffraction

We use a combination of classical molecular dynamics simulation and neutron diffraction to identify the atomic structure of five different Mg–Zn–Ca bulk metallic glasses, covering a range of compositions with substantially different behaviour when implanted in vitro. There is very good agreement between the structures obtained from computer simulation and those found experimentally. Bond lengths and the total correlation function do not change significantly with composition. The zinc and calcium bonding shows differences between composition: the distribution of Zn–Ca bond lengths becomes narrower with increasing Zn content, and the preference for Zn and Ca to avoid bonding to themselves or each other becomes less strong, and, for Zn–Ca, transforms into a positive preference to bond to each other. This transition occurs at about the same Zn content at which the behaviour on implantation changes, hinting at a possible structural connection. A very broad distribution of Voronoi polyhedra are also found, and this distribution broadens with increasing Zn content. The efficient cluster packing model, which is often used to describe the structure of bulk metallic glasses, was found not to describe these systems well

Structural characterisation of bioactive glasses

Bioactive glasses are of great importance for orthopaedic and dental applications. The macroscopic properties of bioactive glasses, and in particular the rate of dissolution, can be tailored for specific applications by altering the compositions. It is therefore important to understand a compositional-structural-relationship as this will help when predicting glass properties and for optimising the design of future glasses for clinical applications. This thesis focused on the structural-characterisation of a wide range of bioactive glasses that are important for orthopaedic and dental applications. Experimental probes including neutron diffraction, high energy X-ray diffraction, solid-state NMR, supported by complimentary techniques such EXAFS, FTIR, XPS and XRD were used to characterise these glasses. A series of halide containing (CaF2 and CaCl2) bioactive glasses were successfully synthesised and characterised. Despite conflicting reports in the literature, the present study strongly suggests that minimal Si-Cl or Si-F bonds are present in these glasses. Instead halide ions were found to surround calcium ions. The silica network is therefore unaffected by the addition of halides ions. A series of novel zinc silicate-germanate glasses, with potential applications for bone cements, were investigated structurally. Studies revealed both Zn and Ge cations are in a tetrahedra coordination with no evidence of 5, 6-fold coordinations. An increase in the network connectivity of the glass will significant reduce its dissolution. The impact of incorporating Mg and Zn into bioglass was studied since both these ions can act as network intermediates. Whilst Zn was found to be solely tetrahedral Mg had significant fractions of 5 and 6-fold coordinations. The structure of Mg-BMG were investigated using neutron diffraction and molecular dynamics to help deconvolved overlapping partial structure factors. Isotopic neutron diffraction was further used to simplify the individual partial structure factors to further understand the structure of the glasses which is important to optimise its properties