Development and optimization of novel bioactive cements for higher cytocompatibility

Abstract

Although the bone has the ability to heal itself, certain bone fractures may not be able to heal properly. In such cases, a bone graft is required to help the process of healing. Different kinds of grafts are already utilized, such as natural grafts from a donor or synthetic grafts made from biomaterials. Biomaterials can be further categorized into metals, polymers, bioceramics and composites. The goal of this thesis was to improve the cytocompatibility of a previously developed bioac-tive cements while maintaining an appropriate ion release to promote bone regeneration. The developed bioactive cements consist of the bioactive glass 1393B20, tricalcium phosphate (TCP) and chitosan. The optimal ratios of the aforementioned components are investigated for reduced cytotoxic effects. The bioactive cements were prepared using different 1393B20/TCP and solid-to-liquid ratios. Cell viability and proliferation tests were first conducted to assess cell response of the cements. The cement composition ratios were then modified and characterized by mechanical, dissolu-tion and bioactivity tests, Fourier Transform InfraRed (FTIR) and X-Ray Fluorescence (XRF) analysis. The cells, on cements containing only the bioactive glass, exhibit a cytotoxic effect, as con-firmed by the extensive ion release measured by ICP-OES. Addition of TCP at the expense of the bioactive glass was hypothesized to reduce the ion release and decrease cytotoxicity. In-deed, a decrease in the glass content led to a decrease in ion release and, subsequently, a de-creased cytotoxicity. Thus, solid-to-liquid ratios were further modified to decrease cytotoxic ef-fects. However, the manufacturing protocol was not reproducible due to breakage of the sam-ples. After changing to a reproducible protocol, the ICP-OES analysis of the chosen composi-tions did not show a strong ion release as previously seen. They also revealed an increase in calcium concentration and a decrease in the phosphorus concentration, as a function of immer-sion time, presumably related to hydroxyapatite (HA) formation. A change in compression strength and behaviour of the cements after immersion in simulated body fluid (SBF) was ob-served, with the cements shifting to a brittle behaviour. The chemical analysis of the cements before immersion using FTIR spectroscopy indicated the presence of each component. This means that the components do not degrade significantly during the manufacturing. XRF results allowed the quantification of the Ca/P ratio at the surface of the cements, after immersion in SBF. Composition with 75wt% of glass and 25wt% of TCP mixed at 1g/ml of chi-tosan, exhibits precipitation of a reactive layer with a ratio close to the one reported for natural HA.