Precise modulation of dissolution, therapeutic ion release, and biocompatibility in bioactive glasses

Abstract This study investigates the controlled dissolution and ion release kinetics of multicomponent borate glasses within the borate anomaly, focusing on therapeutic ions such as calcium, zinc, and fluorine, which are critical in applications ranging from cancer therapy to bone regeneration and oral health. A Design of Mixtures (DoM) statistical modeling approach was employed to systematically evaluate the effects of glass composition on dissolution, ion release, and cytotoxicity. By synthesizing 23 glass formulations, the study demonstrates how statistical modeling enables precise prediction and control of material properties, revealing key interactions between components that are difficult to identify using traditional methods. Notably, higher ZnO content stabilized the glass network, reducing dissolution and ion release rates. The approach also uncovered complex synergies between zinc, titanium, and calcium, emphasizing the value of a multifactorial approach in optimizing glass performance. While higher ZnO concentrations (i.e., 16–20 mol%) correlated with increased cytotoxicity in human umbilical vein endothelial cells (HUVECs), several formulations exhibited no cytotoxic effects at a concentration of 0.2 g/mL, highlighting the need for careful compositional tuning. This research demonstrates how integrating experimental and computational methods can permit the design of glasses with tailored dissolution and ion release kinetics, enabling more effective, customizable, and personalized medical treatments.