Centre for Craniofacial and Regenerative Biology, King's College London, London SE1 9RT, UK.
Otto Schott Institute of Materials Research, Friedrich Schiller University Jena, Fraunhoferstr. 6, 07743 Jena, Germany.
Dent Mater. 2019 Jun;35(6):919-927. doi: 10.1016/j.dental.2019.03.008. Epub 2019 Apr 8.
Wnt/β-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.
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.
We found that although LiPBG and LiBBG can both quickly release Li at concentrations known to regulate Wnt/β-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/β-catenin signalling was limited.
These data suggest that identifying a BG composition that can both quickly deliver high concentrations of Li and is non-toxic remains a challenge.
Wnt/β-catenin 信号通路在再生中发挥重要作用，特别是在骨骼和牙齿等硬组织中，其可以被糖原合成酶激酶 3（GSK3）的小分子拮抗剂所调控；然而，小分子在临床上难以传递。锂（Li）也是 GSK3 的拮抗剂，可以掺入生物活性玻璃（BG）中，该物质可用于牙科和骨修复应用，并可快速释放其组成离子进行调整。
在这里，我们创建了含磷（P）和硼（B）的 BG，其中还包含 Li（LiPBG 和 LiBBG），并研究了它们的离子释放动力学以及其溶解离子对小鼠 17IA4 牙髓细胞的毒性。
我们发现，尽管 LiPBG 和 LiBBG 都能以已知可调节 Wnt/β-catenin 信号通路的浓度快速释放 Li，但它们同时释放的 P 和 B 离子对细胞具有高度毒性。只有当相对低浓度的 LiPBG 和 LiBBG 被放置在细胞培养基中时，它们的溶解产物才是无毒的。然而，在这些浓度下，LiPBG 和 LiBBG 调节 Wnt/β-catenin 信号通路的能力有限。
这些数据表明，寻找一种既能快速输送高浓度 Li 又无毒的 BG 组成仍然是一个挑战。
