Novel Biofilm Inhibitors of Oral Streptococci

新型口腔链球菌生物膜抑制剂

基本信息

批准号：
10415981
负责人：
Russell P Pesavento
金额：
$ 13.83万
依托单位：
UNIVERSITY OF ILLINOIS AT CHICAGO
依托单位国家：
美国
项目类别：
财政年份：
2019
资助国家：
美国
起止时间：
2019-07-01 至 2024-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10415981
关键词：
Abscess Adsorption Affect Affinity Ammonium Animal Model Area Bacteria Biological Biological Assay Caries prevention Cell Survival Cells Cellular Assay Cerium Chemical Models Chemicals Child Childhood Chronic Disease Clinical DNA Dental Dental Care Dental Enamel Dental Pulp Dental caries Dentin Dentistry Development Disease Electron Microscopy Electron energy loss spectroscopy Enzyme Inhibition Enzymes Epithelial Cells Esthetics Etiology Exhibits Exposure to Fibroblasts Foundations Future Gingiva Glucosyltransferases Goals Growth Health HepG2 Hepatocyte Human Hydrolysis Hydroxyapatites In Vitro Investigation Ion Exchange Literature Mentors Methodology Methods Microbial Biofilms Modeling NBL1 gene Oral Oral Medicine Oxidants Oxides Patients Phosphoric Monoester Hydrolases Polysaccharides Preventive Production Research Research Personnel Resolution Saliva Salts Scanning Silver Societies Sodium Chloride Spectrum Analysis Stains Streptococcus Streptococcus mutans Streptococcus sobrinus Structure Study models Surface Techniques Testing Time Tissues Tooth Loss Tooth structure Topical application Toxic effect Translations Transmission Electron Microscopy Work absorption antimicrobial bactericide base cerium oxide nanoparticle clinical application cost effective demineralization efficacy testing extracellular high resolution imaging human tissue inhibitor intestinal epithelium low socioeconomic status macromolecule microbiota nanoparticle novel oral pain oral streptococci pediatric patients self esteem standard of care tooth surface translational model treatment choice

项目摘要

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.

项目概要/摘要龋齿是当今社会最常见的儿童疾病，未经治疗会导致龋齿。口腔疼痛、脓肿发展、牙齿脱落和美观不良都会影响患者的健康和自尊儿童的牙科修复手术是治疗龋齿的标准护理方法，但往往是这样。对于那些社会经济地位较低的儿童来说，长期有效的预防方法是不可行的。对于无法定期去看牙科专业人员的患者来说，这是一种选择。患者的感染归因于牙源性生物膜，包括变形链球菌和远缘链球菌。基于细菌的病因学导致人们转向牙齿使用的杀菌银 (Ag) 制剂作为一种成本- 预防龋齿的有效方法然而，银的使用与牙齿染色、组织毒性和相关性有关。微生物群的破坏使人们对其重复应用和长期使用产生疑问。提出了氧化铈纳米粒子（CeO2-NP）作为口腔非杀菌生物膜抑制剂的第一个例子初步结果表明 CeO2- 对链球菌和 S. sobrinus 具有体外生物膜抑制作用。采用当前方法制备的 Ce(IV) 铵盐水解制备的 NP 已得到展示。与当前局部用药标准 AgNO3 相比，在限制体外生物膜形成方面具有更高的功效重要的是，CeO2-NP 的生物膜抑制机制是非-的。与 AgNO3 不同的是，牙齿应用制剂的一个重大挑战是保持临床效果。该提案的独特之处在于它不仅提出了非浓缩。用于牙齿应用的杀菌生物膜抑制剂，而是一种将它们保留在牙釉质表面以保持持久性的方法铈盐对羟基磷灰石具有众所周知的亲和力，并且已被证明可以在较长时间内发挥作用。羟基磷灰石是一种动态的酸性挑战，可以限制牙釉质表面的脱矿（侵蚀）。结构可通过简单的局部处理促进不同尺寸的离子和纳米颗粒的表面化学交换鉴于 Ce 剂对牙釉质表面的已知亲和力，我们建议加入该提案的新型生物膜抑制剂CeO2-NP通过吸附作用到牙釉质表面。该提案的目的是研究 CeO2-NP 抑制生物膜的潜在细胞外机制以及 CeO2-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研究。