Objectives

Glass ionomer cements (GIC) can be used to protect dentine following caries removal. However, GIC have little biological activity on biological repair processes, which means that neo-dentine formation remains reliant on limited endogenous regenerative processes. Wnt/β-catenin signalling is known to play a central role in stimulating tertiary dentine formation following tooth damage and can be stimulated by a range of glycogen synthase kinase (GSK3) antagonists, including lithium ions.

Methods

Here, we created lithium-containing bioactive glass (BG) by substituting lithium for sodium ions in 45S5 BG. We then replaced between 10 and 40% of the powder phase of a commercial GIC with the lithium-substituted BG to create a range of formulations of ‘LithGlassGIC’. In vitro physical properties of the resulting glasses were characterised and their ability to stimulate reactionary dentine formation in mouse molars in vivo was tested.

Results

Lithium release from LithGlassGIC increased with increasing lithium content in the cement. In common with unmodified commercial GIC, all formations of LithGlassGIC showed in vitro toxicity when measured using an indirect cell culture assay based on ISO10993:5, precluding direct pulp contact. However, in a murine non-exposed pulp model of tooth damage, LithGlassGIC quickly released lithium ions, which could be transiently detected in the saliva and blood. LithGlassGIC also enhanced the formation of tertiary dentine, resulting in a thickening of the dentine at the damage site that restored lost dentine volume. Dentine regeneration was likely mediated by upregulation of Wnt/β-catenin activity, as LithGlassGIC placed in TCF/Lef:H2B-GFP reporter mice showed enhanced GFP activity.

Significance

We conclude that LithGlassGIC acts as a biological restorative material that promotes tertiary dentine formation and restores tooth structure.

中文翻译：

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一种改良的玻璃离子水门汀介导牙本质修复

目标

玻璃离子水门汀 (GIC) 可用于在去除龋齿后保护牙本质。然而，GIC 在生物修复过程中几乎没有生物活性，这意味着新牙本质的形成仍然依赖于有限的内源性再生过程。众所周知，Wnt/β-catenin 信号传导在刺激牙齿损伤后的三级牙本质形成中起着核心作用，并且可以被一系列糖原合酶激酶 (GSK3) 拮抗剂刺激，包括锂离子。

方法

在这里，我们通过在 45S5 BG 中用锂代替钠离子来制造含锂生物活性玻璃 (BG)。然后，我们将商业 GIC 的 10% 至 40% 的粉末相替换为锂取代的 BG，以创建一系列“LithGlassGIC”配方。表征了所得玻璃的体外物理特性，并测试了它们在体内刺激小鼠磨牙中反应性牙本质形成的能力。

结果

LithGlassGIC 释放的锂随着水泥中锂含量的增加而增加。与未修改的商业 GIC 一样，当使用基于 ISO10993:5 的间接细胞培养测定法测量时，所有 LithGlassGIC 的形成都显示出体外毒性，排除了直接接触牙髓。然而，在牙齿损伤的小鼠非暴露牙髓模型中，LithGlassGIC 快速释放锂离子，可以在唾液和血液中瞬时检测到锂离子。LithGlassGIC 还增强了三级牙本质的形成，导致损伤部位的牙本质增厚，从而恢复了失去的牙本质体积。牙本质再生可能是由 Wnt/β-catenin 活性的上调介导的，因为放置在 TCF/Lef:H2B-GFP 报告小鼠中的 LithGlassGIC 显示出增强的 GFP 活性。

意义

我们得出结论，LithGlassGIC 作为一种生物修复材料，可促进三级牙本质形成并修复牙齿结构。