Enhancing the effect of fluoride for root caries control in high-risk older adults

项目摘要/摘要 问题：随着人口老龄化，在全球范围内保持良好的口腔健康的挑战将会增加。 全身并发症(高血压、糖尿病、神经退行性疾病)增加了局部因素，如 因为暴露在更易受影响的牙根表面，以及使用会导致牙根发育不全的药物。 总而言之，这些因素增加了龋齿的发生率，特别是根面龋齿，并降低了口腔健康和质量 老年人的生活。由于口腔健康和一般健康是不可分割的，老年人的口腔健康结果很差 与增加的虚弱和死亡率有关。克服根面龋患率上升的挑战 老年人包括缺乏控制根面龋齿的具体方法，护理标准是 高氟牙膏配方。这些牙膏的临床效果不是很好，因为 氟化物在生物膜中的滞留率并没有随着产品中氟化物浓度的增加而成比例增加。 增加。尽管几十年来氟化物一直是最有效的防龋剂， 令人惊讶的是，没有任何创新来提高其防腐效果。假设：我们设计了一种新的 治疗能够增强氟化物的防腐效果，同时保持其剂量和安全性。在试行中 研究中，我们观察到这种治疗，包括使用氟化物纳米颗粒，增加了大约 氟在致龋性生物膜中的渗透率和滞留率提高100倍，并显示出改善的氟化物- 发布配置文件。因此，我们假设带正电的纳米颗粒将穿透致龋齿。 生物膜，与带负电的生物膜成分结合，并释放足够高的氟化物以改善 氟化物的物理化学效应(控制根面龋齿所需)以及通过以下方式抑制产酸 生物膜(减少产酸物种的优势，即生物膜生态失调)。这一假说将 在以下具体目标中进行测试：S.A.#1：定义治疗之间的相互作用机制 成分和牙科生物膜；S.A.#2：确定治疗对根面牙本质脱矿的影响； S.A.#3：使用活体啮齿动物龋齿模型建立龋病控制疗法的有效性和安全性。 意义：在这个项目成功完成后，我们将了解新的预防潜力 降低牙科生物膜致龋性，控制根面龋病的防龋途径。这部作品具有 对控制龋病高危人群的龋病进展产生长期影响的潜力 并改善患有肥胖症的老年人的健康和生活质量。

PROJECT SUMMARY/ABSTRACT The problem: With an aging population, challenges to maintain good oral health are set to increase worldwide. Systemic complications (high blood pressure, diabetes, neurodegenerative disorders) add to local factors, such as the exposure of the more susceptible root surfaces and the use of medications that cause hyposalivation. Collectively, these factors increase caries rates, especially root caries, and reduce the oral health and quality of life of older adults. As oral and general health are indivisible, poor oral health outcomes in older individuals are associated with increased frailty and mortality. Challenges to overcome the increased rate of root caries in older adults include the lack of a specific approach for root caries control, the standard of care being the prescription of high fluoride toothpastes. These toothpastes have modest clinical effectiveness, since the retention of fluoride in the biofilm is not proportionally enhanced as the fluoride concentration in the product increases. Although fluoride has been the most effective agent for caries prevention for several decades, surprisingly, no innovations to improve its anticaries efficacy have been made. Hypothesis: We devised a new therapy able to enhance the anticaries effect of fluoride, while maintaining its dose and safety profile. In pilot studies, we observed that this therapy, involving the use of fluoride nanoparticles, increase by approximately 100-fold the penetration and retention of fluoride in cariogenic biofilms, and exhibit an improved fluoride- releasing profile. Thus, we hypothesize that the positively charged nanoparticles will penetrate the cariogenic biofilm, bind to negatively charged biofilm components, and release fluoride at levels high enough to improve the physicochemical effect of fluoride (needed for the control of root caries) as well as inhibit acid production by the biofilm (reducing the predominance of acid-producing species, i.e. biofilm dysbiosis). This hypothesis will be tested in the following specific aims: S.A.#1: Define the mechanisms of interaction between the therapy components and dental biofilm; S.A.#2: Determine the effects of the therapy on root dentin demineralization; S.A.#3: Establish the efficacy and safety of the therapy for caries control using in vivo rodent caries models. Significance: Upon successful completion of this project, we will understand the preventive potential of a new anticaries approach to reduce the cariogenicity of dental biofilm and control root caries. This work has the potential to exert a long-lasting impact on the control of rampant caries progression in high caries-risk groups and improve the health and quality of life of older adults suffering from hyposalivation.