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Biomaterial-induced mild alkaline microenvironments can positively affect osteoblast activity, contributing to bone regeneration. However, the challenge associated with silicate bioactive glasses, including melt-derived 45S5 Bioglass (45S5-Glass) and sol–gel bioactive glasses, lies in the rapid release of cations in the early stage, resulting in a significant increase in the local pH, which could induce inflammatory reactions and even hinder the process of bone regeneration. Therefore, it is crucial to develop bioactive glass with mild alkaline capacity and a moderate release rate of bioactive ions. In this study, a novel class of bioactive glass (SP-Glass, CaTiSiO5 glass) is fabricated via a containerless melting approach to avoid phase separation and heterogeneous nucleation during the glass formation process. Compared with 45S5-Glass, the network structure of SP-Glass is more stable, resulting in a significant reduction in the pH value and release rate of bioactive ions. SP-Glass creates a favorable mildly alkaline microenvironment for promoting the osteogenic differentiation of osteoblasts while inhibiting osteoclastic activity. Moreover, SP-Glass facilitates the shift of macrophages from the proinflammatory M1 state to the anti-inflammatory M2 state and promotes bone regeneration in vivo. Therefore, containerless melting-prepared bioactive glasses with mild alkalinity combine excellent biocompatibility and bone-forming bioactivity, representing a new class of bioactive materials for tissue regeneration.

This is an open access article under the terms of the Creative Commons Attribution 4.0 International License (CC BY 4.0, http://creativecommons.org/licenses/by/4.0/).
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