There is an ingoing need for more effective and less costly bone substitute materials. In a previous study, addition of titanium dioxide (TiO2) up to 5 mol.% was shown to be effective in controlling glass degradation, and this was reflected in enhanced gene expression and bone-forming capacity of phosphate-based glasses. In the current study, incorporation of the maximum possible amount of TiO2 has been attempted in order to further improve the biological response of these glasses. This report describes the physical, surface properties and short-term response of an osteoblast cell line (MG63) on phosphate glasses doped with the maximum possible TiO2 content. The results showed that a maximum of 15 mol.% TiO2 can be incorporated into the ternary formulations while maintaining their amorphous nature; such incorporation was associated with a significant increase in density and glass transition temperature. On crystallization, X-ray diffraction analysis showed the presence of TiP2O7 and NaCa(PO3)3 as the main phases for all TiO2-containing glasses, while beta-(CaP2O6) was only detected for 10 and 15 mol.% TiO2 glasses. The degradation rate, however, was significantly reduced by an order of magnitude with incorporation of 10 and 15 mol.% TiO2, and this was reflected in the released ions. This change in the bulk properties, produced with TiO2 incorporation, was also associated with a significant change in the hydrophilicity and surface reactivity of these glasses. Even though the addition of TiO2 reduced the hydrophilicity and the surface free energy of these glasses compared to TiO2 free composition, TiO2-containing glasses still have a significantly reactive surface layer compared to Thermanox. Generally glasses with 5-15 mol.% TiO2 supported MG63 cell growth and maintained high cell viability for up to 7 days culture, which is comparable to Thermanox. Based on the results obtained from this study, TiO2-containing phosphate glasses are promising substrates for bone tissue engineering applications.