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.

项目摘要/摘要龋齿是当今社会中最常见的儿童疾病。未经处理的龋齿有助于口腔疼痛，脓肿发育，牙齿脱落和不良的美学影响，影响健康和自尊心孩子们。恢复性牙齿程序是治疗龋齿的护理标准，但通常是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在这样的患者中选择的选择，这些患者无法常规见牙科专业人员。牙科的病因在小儿携带患者归因于完成链球菌突变和Sobrinus链球菌的生物膜。这基于细菌的病因已导致临床医生转向牙齿申请的细菌银（Ag）剂作为成本 - 逮捕牙科车的有效方法。但是，AG的使用与牙齿染色，组织毒性和造成菌群的破坏质疑其重复应用和长期使用。这个建议以口服的非细菌生物膜抑制剂为例，以氧化葡萄纳米颗粒（CEO2-NP）为例链球菌。初步结果表明，通过CEO2-对突变链球菌和Sobrinus的体外生物膜抑制作用。由CE（IV）铵盐水解制备的NP。由当前方法准备的CEO2-NP已暴露与AGNO3相比小儿牙科的治疗可逮捕。重要的是，CEO2-NP抑制生物膜的机制是非 - 与AgNO3相反的杀菌性。牙齿涂剂的重大挑战是维持临床药剂在牙齿表面的有效浓度。该提议的独特之处在于，它不仅规定了非 - 杀菌生物膜抑制剂用于牙齿施用，但一种将其保留在搪瓷表面的方法长时间。瓷沙拉对羟基磷灰石具有众所周知的亲和力，已被证明牙釉质表面的限制脱矿化（侵蚀），并具有酸性挑战。羟基磷灰石是一种动态促进离子和纳米颗粒的表面化学交换变化的结构，简单局部行政。鉴于CE代理对搪瓷表面的已知亲和力，我们提出了新型生物膜通过吸附在牙釉质表面上抑制CEO2-NP剂。该提案的目标是研究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有效研究。