In this study, S53P4 (53SiO2-23Na2O-20CaO-4P2O5) bioactive glass (BG) were prepared through a melt-milling process, and their bioresorption and biomineralization behavior was evaluated by in vitro dissolution under different solution conditions (neutral and acidic). The particle size of S53P4 BG was controlled by milling, and the in vitro dissolution evaluation was performed in tris buffer and citric acid solution for 21 days at 37 °C according to ISO 10993-14 (biological evaluation of medical devices). During dissolution, the ion release rate of S53P4 BG was confirmed to be three times faster in citric acid solution than that in tris buffer. Among them, the ion concentration of calcium and phosphorus initially increased and then gradually decreased, which is due to the biomineralization process. This process formed a new layer of particles on the surface of S53P4 BG, which was identified as a calcium-phosphate-based compound by X-ray diffraction analysis. Furthermore, the thickness of the layer was observed to be 273 nm in tris buffer and 34 nm in citric acid solution by focused-ion beam scanning electron microscopy, and the morphology of the particles comprising this layer was observed to be thicker and longer in tris buffer than that in citric acid solution. This difference is due to the citrate present in the citric acid solution interacting with the released calcium ions and inhibiting the formation of a new layer. Thus, the ion release of S53P4 BG was faster in citric acid solution than that in tris buffer, but the biomineralization process to form the calcium phosphate-based compound was more effective in tris buffer.
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