## 2 Materials and Methods  
Fabrication of SiO\({}_{2}\) powders was done by mixing tetraethoxysilane (TEOS), ethanol, water, and ammonium. Bioactive glass (BG) was synthesized by mixing TEOS, ethanol, and citric acid with various Ca and P ions added using the sol-gel method. In order to enhance bioactivity, calcium nitrate tetrahydrate (Ca(NO\({}_{3}\))\({}_{2}\)) and diammonium hydrogen phosphate ((NH\({}_{4}\))\({}_{2}\)HPO\({}_{4}\)) were added. The formula of SiO\({}_{2}\) and BG was the same as that described in our previous study [11]. The titanium oxide added was in the form of tetrabutyl titanate (TBOT), and it was directly added into the solution to form TiO\({}_{2}\) composition from the hydrolysis of TBOT. The samples of BG\({}_{-}\)Ti100 were prepared with an Si/Ti molar ratio of 10:1 for raw materials. The titanium oxide amount in the samples of BG\({}_{-}\)Ti75, BG\({}_{-}\)Ti50, and BG\({}_{-}\)Ti25 were sequentially reduced to 75%, 50%, and 25% of BG\({}_{-}\)Ti100, respectively. After the sol-gel process, all the samples were calcinated at 500 \({}^{\circ}\)C for 6 h to get the biocercamics composed of silica and titanium oxide powders. Field-emission scanning electron microscopy (FE-SEM, AURIGA, Zeiss, Germany) was used to observe the microstructure and morphology of samples. The chemical composition was measured by using an energy dispersive X-ray spectrometer (EDS) [12]. X-ray diffraction (XRD) spectra were used to identify the crystal structure through an XRD diffractometer (Bruker AXS Gmbh, Karlsruhe, Germany) operating at 40 kV and 40 mA (Cu K\(\alpha\) = 1.54184 A as the radiation source). The diffraction patterns were collected over a 20 range from 10\({}^{\circ}\) to 50\({}^{\circ}\), with an incremental step size of 0.02\({}^{\circ}\). In the in vitro bioactivity test, 250 mg samples were soaked in 50 mL of simulated body fluid (SBF) [13] to evaluate the ability for biomimetic mineral deposition. The SBF was prepared by dissolving NaCl, KCl, CaCl\({}_{2}\), MgCl\({}_{2}\), HCl, NaHCO\({}_{3}\), K\({}_{2}\)HPO\({}_{4}\), and Na\({}_{2}\)SO\({}_{4}\) in deionized water with a molar concentration of 142, 5.0, 2.5, 1.5, 148, 4.2, 1.0, and 0.5 mM for Na\({}^{+}\), K\({}^{+}\), Ca\({}^{2+}\), Mg\({}^{2+}\), Cl\({}^{-}\), HCO\({}_{3}\)\({}^{-}\), HPO\({}_{4}\)\({}^{2-}\), and SO\({}_{4}\)\({}^{2+}\), respectively. The SBF was buffered to a pH of 7.40 with a 37 wt.% HCl solution [14]. After soaking in SBF for 7 days, the samples were taken out and dried at 60 \({}^{\circ}\)C for morphology observation and chemical composition measurement. The SBF solution immersed with various samples for 0, 1, 4, and 7 days were taken to measure the pH value and ion release concentrations. Inductively coupled plasma mass spectrometry (ICP-MS, ELEMENT XR, Thermo Fisher Scientific Inc, Waltham, MA, USA) was used for the measurement of precise elemental ratios at low concentrations, so the solution was required to be diluted 100 times at the \(\upmu\)g/g (ppm) level. The proposed silica-based biocercamics have a high reactivity with water solutions, and ions released from materials rapidly exchanged with the surrounding environment to lead to the incremental increase of the pH value. It is a positive effect for hydroxyl-carbonate-apatite formation, but it makes the pH-dependent cytotoxicity become a significant issue to evaluate the bioactivity of materials [15]. Therefore, the human osteosarcoma cells (MG63, ATCC(r) CRL-1427 TM) were used in this study to evaluate cell viability [16]. Dulbecco's modified Eagle medium (DMEM) was used for MG63 cells. The medium contained 10% fetal bovine serum (FBS, Gibco(r), Thermo Fisher Scientific Inc, Waltham, MA, USA), and cells were incubated in an incubator at 37 \({}^{\circ}\)C with 5 % CO\({}_{2}\). The culture medium was changed every other day. Cell subculture was prepared using trypsin-EDTA solution. The testing samples were immersed in medium at 37 \({}^{\circ}\)C for 1 day to extract the samples.