Novel Biofilm Inhibitors of Oral Streptococci

项目概要/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，牙齿脱落和影响健康和自尊的不良美学 孩子修复性牙科手术是治疗龋齿的护理标准，但通常 对于那些社会经济地位低下的孩子来说是不可行的。持久的预防方法是治疗 这是不能常规看牙科专业人士的患者的首选。儿童龋病的病因分析 患者的牙齿脱落归因于牙源性生物膜，包括变形链球菌和远缘链球菌。这 基于细菌的病因学导致临床医生转向牙齿应用的杀菌银（Ag）剂作为成本- 有效预防龋齿方法。然而，银的使用与牙齿染色、组织毒性和 微生物群的破坏，使人们对其重复应用和长期使用提出质疑。这项建议 阐述了氧化铈纳米颗粒（CeO 2-NP）作为口腔粘膜的非杀菌性生物膜抑制剂的第一个实例， 链球菌初步结果表明体外生物膜对S. mutans和S. sobrinus由CeO 2- 通过Ce（IV）铵盐水解制备NP。通过当前方法制备的CeO 2-NP表现出 与AgNO 3相比，在限制体外生物膜形成方面具有更高的功效，AgNO 3是目前用于局部给药的标准， 治疗小儿龋病。重要的是，CeO 2-NP抑制生物膜的机制是非生物降解的。 与AgNO 3相反的杀菌剂。牙齿应用剂的一个重大挑战是保持临床上的 在牙齿表面的有效浓度。这项提案的独特之处在于，它不仅提出了非-- 用于牙齿应用的杀菌生物膜抑制剂，但是将它们保留在牙釉质表面以用于治疗的方法， 延长时间。众所周知，铈盐对羟基磷灰石具有亲和力，并且已被证明可以 用酸性挑战限制釉质表面的脱矿（侵蚀）。羟基磷灰石是一种动态 该结构促进不同尺寸的离子和纳米颗粒的表面化学交换， 局考虑到Ce试剂对牙釉质表面的已知亲和力，我们建议将 本发明的新型生物膜通过吸附将本发明的CeO 2-NP试剂抑制到牙釉质表面上。的 该建议的目的是研究CeO 2-NP抑制生物膜的潜在细胞外机制 以及CeO 2-NP与羟基磷灰石表面的化学相互作用及其在翻译模型中的功效 问题研究

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.