In Situ Synchrotron X-ray Diffraction Analysis of the Setting Process of Brushite Cement: Reaction and Crystal Growth

Brushite cements are fast self-setting materials that can be used as bone substitute materials. Although tracing their fast setting process is a challenge, it is important for the understanding of the same, which in turn is important for the material's further development and use in the clinics. In this study, the setting rate, phase formation, and crystal growth of brushite cements were quantitatively studied by in situ synchrotron powder X-ray diffraction (SXRD) on a time scale of seconds. The influence of reactant ratios and a retardant (citric acid) on the setting reaction were analyzed. To complement the in situ investigations, scanning electron microscopy was carried out for ex situ morphological evolution of crystals. The initial reaction followed a four-step process, including a fast nucleation induction period, nucleation, crystal growth, and completion of the setting. The brushite crystal size grew up to the micro scale within 1 min, and the brushite content increased linearly after the nucleation until all monocalcium phosphate monohydrate (MCPM; Ca(H₂PO₄)₂·H₂O) had dissolved within minutes, followed by a slow increase until the end of the monitoring. By adjusting the MCPM to the β-tricalcium phosphate (β-TCP, β-Ca₃(PO4)₂) ratio in the starting powders, the brushite/monetite ratio in the cements could be modified. In the presence of citric acid, the formation of brushite nuclei was not significantly retarded, whereas the increase in brushite content and the growth of crystal size were effectively hindered. The amount of monetite also increased by adding citric acid. This is the first time that the brushite setting process has been characterized in the first seconds and minutes of the reaction by SXRD.