From atomic scale to biological performance: the role of magnesium in solubility of the network and bioactivity of 45S5 Bioglass®

• MD+SBF experiments map MgO (0–20 mol%) effects in 45S5 Bioglass®. • Network connectivity rises with MgO (NC 1.926→2.035), strengthening the glass. • Ion-clustering R-factors show maximal cation homogeneity at intermediate MgO (45-M5). • 45-M5 shows balanced Si/Mg release and moderate pH shift after 24 h in SBF. • FE-SEM confirms uniform, rapid hydroxyapatite formation on the 45-M5 composition. Understanding the multiscale structural behavior of magnesium-doped 45S5 bioactive glasses (BGs) is essential for optimizing their performance in tissue engineering and bone regeneration. In this study, eight compositions (45-M0 to 45-M20) with 0-20 mol% MgO were investigated using a combined molecular dynamics (MD) simulation and experimental analysis. The MD results showed that network connectivity (NC) increased from 1.926 in 45-M0 to 1.953 in 45-M5, and then to 2.035 in 45-M20. The ion clustering (R-factor) analysis showed that the most homogeneous cation distribution occurs in the 45-M5 compound, which exhibits the lowest Ca–Ca and Mg–Mg aggregation. The experimental results also confirmed the MD predictions: ICP-AES analysis after 24 hours of immersion in SBF solution showed that 45-M5 had the most balanced ion release and pH change. FE-SEM images also confirmed the uniform and rapid formation of the hydroxyapatite layer in this compound. Taken together, the 45-M5 compound offers an optimal balance between network stability and bioactivity, and was introduced as an optimal MgO content for tissue engineering and bone regeneration applications, and can pave the way for the development of a new generation of tunable BGs.