Novel Biofilm Inhibitors of Oral Streptococci

新型口腔链球菌生物膜抑制剂

• 批准号: 10640889
• 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
• 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/10640889
• 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; Patients; Phosphoric Monoester Hydrolases; Polysaccharides; Postdoctoral Fellow; Predisposition; 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; Transmission Electron Microscopy; Work; absorption; antimicrobial; bactericide; 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

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.

项目总结/文摘

项目成果

Nanoceria Aggregate Formulation Promotes Buffer Stability, Cell Clustering, and Reduction of Adherent Biofilm in Streptococcus mutans.

• DOI: 10.1021/acsbiomaterials.3c00174
• 发表时间: 2023-07
• 期刊: ACS biomaterials science & engineering
• 影响因子: 5.8
• 作者: K. Ellepola;L. Bhatt;Lin Chen;Chen Han;Forough Jahanbazi;R. Klie;Francisco J. Lagunas Vargas;Yuanbing Mao;Kirill Novakovsky;Bibash Sapkota;R. Pesavento