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、牙齿脱落和美观不良都会影响患者的健康和自尊 孩子们。修复性牙科手术是治疗龋齿的标准护理方法，但通常是 对于那些社会经济地位较低的儿童来说不可行。持久的预防方法才是治疗方法 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。小儿龋齿的病因 患者的感染归因于包含变形链球菌和远缘链球菌的牙源生物膜。这 基于细菌的病因导致临床医生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 微生物群的破坏使人对其重复使用和长期使用产生疑问。这个提议 提出了氧化铈纳米颗粒（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 S. mutans 和 S. sobrinus 的体外生物膜抑制作用 通过 Ce(IV) 铵盐水解制备 NP。目前方法制备的 CeO2-NP 表现出 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 小儿龋齿停止的治疗。重要的是，CeO2-NP 抑制生物膜的机制是非- 与 AgNO3 相比具有杀菌作用。牙齿应用制剂的一个重大挑战是维持临床效果 药剂在牙齿表面的有效浓度。该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，而是一种将它们保留在牙釉质表面以保持持久性的方法 延长的一段时间。铈盐对羟基磷灰石具有众所周知的亲和力，并已被证明可以 限制酸性挑战下牙釉质表面的脱矿质（侵蚀）。羟基磷灰石是一种动态 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 行政。鉴于已知 Ce 剂对牙釉质表面的亲和力，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。这 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。

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