Doxycycline-containing glass ionomer cement for arresting residual caries: an in vitro study and a pilot trial

Abstract In a previous study, we demonstrated that the incorporation of doxycycline hyclate (DOX) into resin-modified glass ionomer cement (RMGIC) inhibited important cariogenic microorganisms, without modifying its biological and mechanical characteristics. In this study, we keep focused on the effect of that experimental material as a potential therapy for arresting residual caries by analyzing other in vitro properties and conducting a pilot clinical trial assessing the in vivo effect of DOX-containing RMGIC on residual mutans streptococci after partial carious removal in primary molars. Specimens of the groups RMGIC (control); RMGIC + 1.5% DOX; RMGIC + 3% DOX; and RMGIC + 4.5% DOX were made to evaluate the effect of DOX incorporation on surface microhardness and fluoride release of RMGIC and against biofilm of Streptococcus mutans. Clinical intervention consisted of partial caries removal comparing RMGIC and RMGIC + 4.5% DOX as lining materials. After 3 months, clinical and microbiologic evaluations were performed. Data were submitted to ANOVA/Tukey or Wilcoxon/Mann-Whitney set as α=0.05. Fluoride release and surface microhardness was not influenced by the incorporation of DOX (p>0.05). There was a significant reduction of S. mutans biofilm over the material surface with the increase of DOX concentration. After clinical trial, the remaining dentin was hard and dry. Additionally, mutans streptococci were completely eliminated after 3 months of treatment with RMGIC + 4.5% DOX. The incorporation of DOX provided better antibiofilm effect, without jeopardizing fluoride release and surface microhardness of RMGIC. This combination also improved the in vivo shortterm microbiological effect of RMGIC after partial caries removal.摘要 既往研究中，我们证实将盐酸多西环素（doxycycline hyclate, DOX）掺入树脂改性玻璃离子水门汀（resin-modified glass ionomer cement, RMGIC）后，可抑制重要的致龋微生物，且不会改变其生物学与机械性能。本研究聚焦于该实验材料作为阻断残余龋的潜在治疗手段的效果，通过分析其他体外性能，并开展一项试点临床试验，评估含DOX的RMGIC在乳牙部分去龋后，对体内变形链球菌（Streptococcus mutans）的作用。我们制备了RMGIC（对照组）、RMGIC+1.5% DOX、RMGIC+3% DOX以及RMGIC+4.5% DOX四组试样，以评估DOX掺入对RMGIC表面显微硬度与氟离子释放性能的影响，及其对变形链球菌生物膜的抑制作用。临床干预环节采用RMGIC与RMGIC+4.5% DOX作为垫底材料，开展部分去龋对比研究。术后3个月时进行临床与微生物学评估。数据采用ANOVA/Tukey检验或Wilcoxon/Mann-Whitney检验进行分析，检验水准设定为α=0.05。DOX的掺入对氟离子释放与表面显微硬度无显著影响（p>0.05）。随着DOX浓度升高，材料表面的变形链球菌生物膜量显著降低。临床试验结束后，剩余牙本质呈现坚硬干燥状态。此外，采用RMGIC+4.5% DOX治疗3个月后，体内变形链球菌群被完全清除。DOX的掺入可提升抗生物膜性能，且不会损害RMGIC的氟离子释放能力与表面显微硬度。该复合体系还可改善乳牙部分去龋后RMGIC的短期体内微生物学效果。