Using molecular dynamic simulation to study the structural role of Cu+ and Cu++ oxides in bioactive glasses for design and fabrication of scaffolds for tissue engineering

Copper oxide containing bioactive glasses have drawn attention because of their unique properties as a biomaterial for targeted tissue engineering applications. This is due to their ability in acting as stimulants to new tissue formation. The aim of this PhD research project is to explore the integration of computational modelling of glass structure, with experimental glass synthesis and in vitro bioactivity evaluation to understand structurebioactivity of Cu-containing glasses. Molecular dynamic simulations have been employed as the most effective methods throughout the project to investigate the influence of Cu ions on the structure of bioactive silicate- and phosphate glasses at the atomic level. The molecular structures of silicate bioactive glasses with compositions 46.1 mol% SiO2, 26.9 mol% CaO, 24.4 mol% Na2O, and 2.6 mol% P2O5, and phosphate bioactive glasses with compositions 2.6 mol% SiO2, 26.9 mol% CaO, 24.4 mol% Na2O, and 46.1 mol% P2O5, in which CuO (10, 15, and 20 mol%) was progressively substituted for Na2O, have been respectively explored. Since copper oxides Cu+ and Cu++ can occur in the glass during thermal treatments,the influence of Cu+ and Cu++ ions simultaneously on the glass structure has been investigated and the ratio of those ions within the glasses has been calculated. A polarisable interatomic potential has been developed for both Cu+-O and Cu++-O interactions using an empirical fitting procedure. Careful structure analysis has been carried out in order to provide an accurate description of the local structure of Cu+ and Cu++ ions for biomaterial applications. The relationship between the structural changes and the bioactivity of glasses after addition of Cu ions, have been studied based on the amount of non-bridging oxygens, and the overall network connectivity of the glass. The findings indicate that both Cu+ ions with three-fold coordinated and Cu++ ions, coordinated by six oxygen atoms, participates in the glass structure as network modifiers. The impact of Cu+ and Cu++ ions on the overall silicate-based glass network connectivity was likely to be small. The findings from computational studies indicate that the number of Cu+ ions increases in silicate glasses with increasing CuO content, whereas, the Cu++ ions increase in phosphate glasses with increasing CuO content.

Glass structural analysis using molecular dynamic simulations show that inclusion of Cu oxides at 46.1 mol% P2O5 will produce invert glasses, where we would not expect substantial changes in the network connectivity or bioactivity after incorporation of the Cu ions in silicate glasses containing 46.1 mol% SiO2, regardless of oxidation state.

In this study, a series of silicate glasses have been synthesised and doped with Cu+ and Cu++ ions. It was followed by fabrication of a series chitosan/Cu-silicate bioactive glasses hybrid scaffolds. The accuracy of finding generated by simulations was validated by comparing various measurements including scanning electron microscopy, X-ray diffraction, X-ray photo-electron spectroscopy and Fourier transform infrared spectrometry and Raman spectroscopy.

The biological response of chitosan/bioglass scaffolds containing Cu+ and Cu++ has been examined using cell culturing method. It has been shown in this dissertation that atomistic computer simulations, when integrated with experimental tools can be an effective tool in understanding and/or designing novel bioactive glass-based materials to control or tailor the bioactivity and other properties for different biomedical applications. Due to the Covid-19 pandemic, the study of Cu-containing phosphate BGs were not performed experimentally.