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.

The positive regulation of bone-forming osteoblast activity and the negative feedback regulation of osteoclastic activity are equally important in strategies to achieve successful alveolar bone regeneration. Here, a molybdenum (Mo)-containing bioactive glass ceramic scaffold with solid-strut-packed structures (Mo-scaffold) was printed, and its ability to regulate pro-osteogenic and anti-osteoclastogenic cellular responses was evaluated in vitro and in vivo. We found that extracts derived from Mo-scaffold (Mo-extracts) strongly stimulated osteogenic differentiation of bone marrow mesenchymal stem cells and inhibited differentiation of osteoclast progenitors. The identified comodulatory effect was further demonstrated to arise from Mo ions in the Mo-extract, wherein Mo ions suppressed osteoclastic differentiation by scavenging reactive oxygen species (ROS) and inhibiting mitochondrial biogenesis in osteoclasts. Consistent with the in vitro findings, the Mo-scaffold was found to significantly promote osteoblast-mediated bone formation and inhibit osteoclast-mediated bone resorption throughout the bone healing process, leading to enhanced bone regeneration. In combination with our previous finding that Mo ions participate in material-mediated immunomodulation, this study offers the new insight that Mo ions facilitate bone repair by comodulating the balance between bone formation and resorption. Our findings suggest that Mo ions are multifunctional cellular modulators that can potentially be used in biomaterial design and bone tissue engineering.

For the therapy and regeneration of bone defects resulting from malignant bone tumors, it is necessary to develop multifunctional biomaterials that are able to deliver therapeutic drugs, monitor drug release, and stimulate bone formation. Herein, a multifunctional mesoporous bioactive glass (MBG)/upconversion nanoparticle (UCNP) nanocomposite [UCNPs@SiO₂@mSiO₂-XCa (X = 0, 5, 10, 15, and 20)] with the ability to deliver anti-cancer drugs, monitor drug release, and stimulate osteogenic differentiation of bone marrow stromal cells (BMSCs) was successfully prepared using a layer-by-layer strategy. The nanocomposite spheres possess a core–shell structure composed of UCNPs and a mesoporous SiO₂/Ca layer with a uniform size distribution of 100 nm. The incorporation of Ca into the nanocomposites induced phase transformation from a pure hexagonal phase to a cubic phase, and facilitated the occurrence of red emission, which significantly improved fluorescence penetration for deep tissue imaging. In addition, since the red emission strongly overlaps with the maximum absorbance of the anti-cancer drug zinc phthalocyanine (ZnPc), red luminescence could be strongly quenched by ZnPc. Consequently, drug release could be quantified by monitoring changes in fluorescence intensity. Furthermore, the incorporation of Ca into MBG/UCNP nanocomposites remarkably improved bioactivity, i.e., it stimulated apatite mineralization in simulated body fluids and enhanced cell proliferation and bone-related gene expression in BMSCs for the concentration range of 200–500 μg/mL. Our results suggest that the prepared MBG/UCNP nanocomposites are useful for the therapy and regeneration of bone defects resulting from malignant bone tumors owing to their distinct multifunctionality, including strong red emission and functions in drug-delivery monitoring and osteostimulation.