The ICIE16-bioactive glass (BG) (48.0 SiO2, 6.6 Na2O, 32.9 CaO, 2.5 P2O5, 10.0 K2O (wt %)) has been developed as an alternative to 45S5-BG, the original BG composition (45.0 SiO2, 24.5 Na2O, 24.5 CaO, 6.0 P2O5 (wt %)), with the intention of broadening the BG sintering window while maintaining bioactivity. Because there is a lack of reports on ICIE16-BG biological properties, the influence of ICIE16-BG on viability, proliferation, and osteogenic differentiation of human mesenchymal stromal cells (MSCs) was evaluated in direct comparison to 45S5-BG in this study. The BGs underwent heat treatment similar to that which is required in order to fabricate scaffolds by sintering, which resulted in crystallization of 45S5-BG (45S5-CBG) while ICIE16 remained amorphous. Granules based on both BGs were biocompatible, but ICIE16-BG was less harmful to cell viability, most likely due to a more pronounced pH alkalization in the 45S5-CBG group. ICIE16-BG outperformed 45S5-CBG in terms of osteogenic differentiation at the cellular level, as determined by the increased activity of alkaline phosphatase. However, granules from both BGs were comparable regarding the stimulation of expression levels of genes encoding for osseous extracellular matrix (ECM) proteins. The addition of therapeutically active ions to ICIE16-BG might further improve its ability to stimulate ECM production and should be investigated in upcoming studies.

Mesoporous bioactive glass nanoparticles (MBGNs) have demonstrated promising properties for the local delivery of therapeutically active ions with the aim to improve their osteogenic properties. Manganese (Mn), zinc (Zn), and copper (Cu) ions have already shown promising pro‐osteogenic properties. Therefore, the concentration‐dependent impact of MBGNs (composition in mol%: 70 SiO2, 30 CaO) and MBGNs containing 5 mol% of either Mn, Zn, or Cu (composition in mol%: 70 SiO2, 25 CaO, 5 MnO/ZnO/CuO) on the viability and osteogenic differentiation of human marrow‐derived mesenchymal stromal cells (BMSCs) was assessed in this study. Mn‐doped MBGNs (5Mn‐MBGNs) showed a small “therapeutic window” with a dose‐dependent negative impact on cell viability but increasing pro‐osteogenic features alongside increasing Mn concentrations. Due to a constant release of Zn, 5Zn‐MBGNs showed good cytocompatibility and upregulated the expression of genes encoding for relevant members of the osseous extracellular matrix during the later stages of cultivation. In contrast to all other groups, BMSC viability increased with increasing concentration of Cu‐doped MBGNs (5Cu‐MBGNs). Furthermore, 5Cu‐MBGNs induced an increase in alkaline phosphatase activity. In conclusion, doping with Mn, Zn, or Cu can enhance the biological properties of MBGNs in different ways for their potential use in bone regeneration approaches.

Due to their high bioreactivity, the in-vitro analysis of bioactive glasses (BGs) can be challenging when it comes to maintaining a physiological pH. To improve BG biocompatibility, a heterogenic spectrum of preconditioning approaches, such as “passivation” of the BGs by incubation in cell culture medium, are used but have never been directly compared. In this study, the effect of passivation periods of up to 72 h on pH alkalization and viability of human bone marrow-derived mesenchymal stromal cells was evaluated to determine a time-efficient passivation protocol using granules based on the 45S5-BG composition (in wt%: 45.0 SiO2, 24.5 Na2O, 24.5 CaO, 6.0 P2O5) in different concentrations. pH alkalization was most reduced after passivation of 24 h. Cell viability continuously improved with increasing passivation time being significantly higher after passivation of at least 24 h compared to non-passivated 45S5-BG and the necessary passivation time increased with increasing BG concentrations. In this setting, a passivation period of 24 h presented as an effective approach to provide a biocompatible cell culture setting. In conclusion, before introduction of BGs in cell culture, different passivation periods should be evaluated in order to meet the respective experimental settings, e.g., by following the experimental protocols used in this study.