Alaohali Abeer, Brauer Delia S, Gentleman Eileen, Sharpe Paul T
Centre for Craniofacial and Regenerative Biology, Faculty of Dentistry, Oral and Craniofacial Sciences, King's College London, UK; Department of Dental and Oral Health, Prince Sultan Military College of Health Sciences, Dammam, Saudi Arabia.
Otto Schott Institute of Materials Research, Faculty of Chemistry and Earth Sciences, Friedrich Schiller University Jena, Germany.
Dent Mater. 2021 Aug;37(8):1307-1315. doi: 10.1016/j.dental.2021.05.003. Epub 2021 Jun 24.
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.
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.
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.
We conclude that LithGlassGIC acts as a biological restorative material that promotes tertiary dentine formation and restores tooth structure.
玻璃离子水门汀(GIC)可用于在龋病去除后保护牙本质。然而,GIC对生物修复过程几乎没有生物活性,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。已知Wnt/β-连环蛋白信号通路在牙齿损伤后刺激第三期牙本质形成中起核心作用,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。
在此,我们通过用锂离子替代45S5生物玻璃中的钠离子来制备含锂生物活性玻璃(BG)。然后,我们用锂替代的BG替换了商业GIC粉末相的10%至40%,以创建一系列“LithGlassGIC”配方。对所得玻璃的体外物理性质进行了表征,并测试了它们在体内刺激小鼠磨牙反应性牙本质形成的能力。
LithGlassGIC中锂的释放随着水门汀中锂含量的增加而增加。与未改性的商业GIC一样,使用基于ISO10993:5的间接细胞培养试验测量时,所有LithGlassGIC制剂均显示体外毒性,排除了直接牙髓接触。然而,在小鼠牙齿损伤的未暴露牙髓模型中,LithGlassGIC迅速释放锂离子,可在唾液和血液中短暂检测到。LithGlassGIC还增强了第三期牙本质的形成,导致损伤部位的牙本质增厚,恢复了丢失的牙本质体积。牙本质再生可能是由Wnt/β-连环蛋白活性的上调介导的,因为置于TCF/Lef:H2B-GFP报告基因小鼠中的LithGlassGIC显示出增强的GFP活性。
我们得出结论,LithGlassGIC作为一种生物修复材料,可促进第三期牙本质形成并恢复牙齿结构。