A comparison of lithium-substituted phosphate and borate bioactive glasses for mineralised tissue repair

Objectives. Wnt/beta-catenin signalling plays important roles in regeneration, particularly in hard tissues such as bone and teeth, and can be regulated by small molecule antagonists of glycogen synthase kinase 3 (GSK3); however, small molecules can be difficult to deliver clinically. Lithium (Li) is also a GSK3 antagonist and can be incorporated into bioactive glasses (BG), which can be used clinically in dental and bone repair applications and tuned to quickly release their constituent ions. Methods. Here, we created phosphate (P)- and borate (B)-based BG that also contained Li (LiPBG and LiBBG) and examined their ion release kinetics and the toxicity of their dissolution ions on mouse 17IA4 dental pulp cells. Results. We found that although LiPBG and LiBBG can both quickly release Li at concentrations known to regulate Wnt/beta-catenin signalling, the P and B ions they concomitantly release are highly toxic to cells. Only when relatively low concentrations of LiPBG and LiBBG were placed in cell culture medium were their dissolution products non-toxic. However, at these concentrations, LiPBG and LiBBG's ability to regulate Wnt/beta-catenin signalling was limited. Significance. These data suggest that identifying a BG composition that can both quickly deliver high concentrations of Li and is non-toxic remains a challenge. (C) 2019 The Authors. Published by Elsevier Inc. on behalf of The Academy of Dental Materials. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).