Toward a Rational Design of Bioactive Glasses with Optimal Structural Features: Composition–Structure Correlations Unveiled by Solid-State NMR and MD Simulations

[Image: see text] The physiological responses of silicate-based bioactive glasses (BGs) are known to depend critically on both the P content (n(P)) of the glass and its silicate network connectivity (N̅(BO)(Si)). However, while the bioactivity generally displays a nonmonotonic dependence on n(P) itself, recent work suggest that it is merely the net orthophosphate content that directly links to the bioactivity. We exploit molecular dynamics (MD) simulations combined with (31)P and (29)Si solid-state nuclear magnetic resonance (NMR) spectroscopy to explore the quantitative relationships between N̅(BO)(Si), n(P), and the silicate and phosphate speciations in a series of Na(2)O–CaO–SiO(2)–P(2)O(5) glasses spanning 2.1 ≤ N̅(BO)(Si) ≤ 2.9 and variable P(2)O(5) contents up to 6.0 mol %. The fractional population of the orthophosphate groups remains independent of n(P) at a fixed N̅(BO)(Si)-value, but is reduced slightly as N̅(BO)(Si) increases. Nevertheless, P remains predominantly as readily released orthophosphate ions, whose content may be altered essentially independently of the network connectivity, thereby offering a route to optimize the glass bioactivity. We discuss the observed composition-structure links in relation to known composition-bioactivity correlations, and define how Na(2)O–CaO–SiO(2)–P(2)O(5) compositions exhibiting an optimal bioactivity can be designed by simultaneously altering three key parameters: the silicate network connectivity, the (ortho)phosphate content, and the n(Na)/n(Ca) molar ratio.