Novel Biofilm Inhibitors of Oral Streptococci

项目摘要/摘要 龋齿是当今社会最常见的儿童疾病。未经治疗的龋齿会导致 口腔疼痛、脓肿发展、牙齿脱落和不良美观都会影响健康和自尊 孩子们。修复性牙科手术是治疗龋齿的标准护理程序，但通常是 对于那些社会经济地位较低的儿童来说，这是不可行的。长效的预防方法是治疗 对于不能定期看牙科专业人员的这类患者来说，这是他们的选择。儿童龋病的病因学研究 患者被归因于牙源性生物膜，包括变形链球菌和远缘链球菌。这 基于细菌的病原学导致临床医生转向牙齿应用的杀菌银(Ag)试剂作为一种成本- 预防龋齿的有效方法。然而，银的使用与牙齿染色、组织毒性和 微生物区系的破坏使人们对它们的重复应用和长期使用产生了疑问。这项建议 阐述了氧化铈纳米颗粒(CeO2-NP)作为口腔非杀菌生物膜抑制剂的第一个例子 链球菌。初步结果表明，CeO2-对变形链球菌和远缘链球菌的体外生物被膜有抑制作用。 用Ce(IV)铵盐水解法制备纳米粒子。用目前的方法制备的CeO2-NP展示了 与目前外用标准硝酸银相比，在限制体外生物被膜形成方面具有更高的有效性 儿童龋齿止蚀的治疗。重要的是，CeO2-NP对生物膜的抑制机制是非 杀菌剂，而不是硝酸银。牙用药物的一个重大挑战是维持临床上的 在牙齿表面的有效浓度。这项建议的独特之处在于，它不仅提出了非 用于牙齿应用的杀菌生物膜抑制剂，但一种将它们保留在牙釉质表面 延长了一段时间。众所周知，铈盐对羟基磷灰石具有亲和力，并已被证明 在酸性条件下限制牙釉质表面的脱矿(侵蚀)。羟基磷灰石是一种动态的 易于不同大小的离子和纳米颗粒表面化学交换的结构，表面处理简单 行政管理。鉴于已知的Ce试剂对牙釉质表面的亲和力，我们建议将 该新型生物膜通过吸附抑制CeO2-NP试剂在牙釉质表面的作用。这个 本研究的目的是探讨CeO2-NP抑制生物被膜的潜在胞外机制。 CeO2-NP与羟基磷灰石表面的化学相互作用及其在平移模型中的作用 学习。

PROJECT SUMMARY/ABSTRACT Dental caries is the most common childhood disease in today’s society. Untreated dental caries contributes to oral pain, abscess development, tooth loss and poor esthetics affecting both the health and self-esteem of children. Restorative dental procedures are the standard of care in the treatment of dental caries yet often are not feasible for those children of low socioeconomic status. Long lasting preventive methods are the treatment of choice in such patients that cannot routinely see dental professionals. The etiology of dental caries in pediatric patients is attributed to tooth-borne biofilms comprising Streptococcus mutans and Streptococcus sobrinus. This bacteria-based etiology has led clinicians to turn to tooth-applied, bactericidal silver (Ag) agents as a cost- effective method to arrest dental caries. However, Ag use is associated with tooth staining, tissue toxicity and disruption of the microbiota calling into question their repeated application and long-term use. This proposal sets forth the first example of cerium oxide nanoparticles (CeO2-NP) as non-bactericidal biofilm inhibitors of oral Streptococci. Preliminary results demonstrate in vitro biofilm inhibition of S. mutans and S. sobrinus by CeO2- NP prepared by Ce(IV) ammonium salt hydrolysis. CeO2-NP prepared by the current methodology have exhibited a higher efficacy in limiting in vitro biofilm formation as compared to AgNO3, the current standard for topical treatment in pediatric dental caries arrest. Importantly, the mechanism of biofilm inhibition by CeO2-NP is non- bactericidal as opposed to AgNO3. A significant challenge of tooth-applied agents is maintaining a clinically effective concentration of the agent at the tooth surface. This proposal is unique in that it sets forth not only non- bactericidal biofilm inhibitors for tooth application, but a method of retaining them at the enamel surface for an extended period of time. Cerium salts have a well-known affinity for hydroxyapatite and have been shown to limit demineralization (erosion) of the enamel surface with acidic challenge. Hydroxyapatite is a dynamic structure that facilitates surface chemical exchange of ions and nanoparticles of varying size with simple topical administration. Given the known affinity of Ce-agents for the enamel surface, we propose the incorporation of the novel biofilm inhibiting CeO2-NP agents of this proposal onto the enamel surface via adsorption. The objectives of this proposal are to investigate potential extracellular mechanisms of biofilm inhibition by CeO2-NP as well as the chemical interaction of CeO2-NP with hydroxyapatite surfaces and its efficacy in translation model studies.