pH-sensitive materials responding to metabolic activities of cariogenic plaque

响应致龋菌斑代谢活动的 pH 敏感材料

• 批准号: 10043261
• 负责人: Xuesong He
• 金额: $ 23.36万
• 依托单位: ADA SCIENCE AND RESEARCH INSTITUTE LLC
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-09-01 至 2021-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10043261
• 关键词: Acids; Adsorption; Area; Bacteria; Biological; Biomass; Bovine Serum Albumin; Buffers; Carbohydrates; Cells; Characteristics; Charge; Chemical Structure; Chlorhexidine; Chronic; Clinical; Collaborations; Communicable Diseases; Crystallization; Data; Dental caries; Dentures; Dietary Carbohydrates; Dyes; Electrons; Environment; Feedback; Fermentation; Fluorescein; Gel Chromatography; Goals; Growth; Implant; In Situ; Infection prevention; Intake; Metabolic; Methods; Microbial Biofilms; Modeling; Molecular Weight; Monitor; Muramidase; Oral; Performance; Polymers; Production; Property; Proteins; Quartz; Reaction; Research; Roentgen Rays; Saliva; Site; Sodium Chloride; Solid; Spectrum Analysis; Stimulus; Sucrose; Surface; Surface Properties; Testing; Tooth structure; Variant; Wettability; antimicrobial; antimicrobial drug; base; cariogenic bacteria; chemical bond; chemical property; combat; cost; covalent bond; demineralization; density; dental resin; design; dysbiosis; environmental change; functional group; hydrophilicity; knowledge of results; lead candidate; light scattering; microbial; microbial community; microbiome; monolayer; multidisciplinary; novel; oral biofilm; oral microbial community; physical property; polymerization; polymicrobial biofilm; prevent; response; restorative resins; single molecule; success; targeted treatment; tool

Abstract: In today’s microbiome era, it is well-recognized that dental caries, one of the most prevalent and costly chronic infectious diseases world-wide, results from dysbiosis of the oral microbiota and the oral environmental changes that cause tooth damage. Specifically, frequent intake of fermentable carbohydrates promotes a progressive shift in microbial composition toward acidogenic and acid-tolerant species. The continual acid- induced demineralization eventually overcomes the buffering capacity and anti-microbial properties of saliva, leading to irreversible tooth destruction. The goal of this proposed research is to develop pH-responsive materials capable of targeted treatment of acid-producing bacteria (t-TAB) and antifouling. Our central hypothesis is that the combination of pH-responsive protein adsorption and acid-enhanced antimicrobial (AM) efficacy will inhibit the attachment and growth of acid-producing bacteria, consequently prevent the accumulation of cariogenic plaque. We propose three specific aims to design, develop, and evaluate the pH-responsive materials capable of altering protein-adsorption and achieving t-TAB. In Specific Aim 1, we will design and prepare Azo-QPS-containing materials that have pH-responsive surface properties. The Azo-QPS compounds have pH-sensitive AM efficacy and t-TAB functions in solution. We will covalently bond Azo-QPS functional groups onto surfaces in the form of single-molecule monolayer or Azo-QPS-polymers, which will produce variant amount of Azo-QPS functional groups/surface area. In addition, by bonding Azo-QPS with a clinically tested AM agent, chlorhexidine (CHX), we will enhance the new materials’ pH-responsive AM efficacy. In Specific Aim 2, we will evaluate the new materials’ performance in terms of pH-responsive reversible protein-adsorption and antifouling. We will enhance our understanding of the correlation between the surface chemical and physical properties and the antifouling performance. Specifically, we will focus on the correlation of hydrophilicity and charge density with the protein-adsorption in response to the pH variation between pH 4-8, a biological relevant pH range in oral environments. In Specific Aim 3, we will assess on-site antifouling and t-TAB efficacy of the new materials in a multispecies biofilm model that simulates oral microbial community. These will be performed in the presence and absence of sucrose—the cariogenic dietary carbohydrate. Strategy will entail evaluating biomass, analyzing microbial profiles and determining environmental pH. The successful completion of the proposed research will yield pH-responsive materials that are antifouling and obtain t-TAB in response to environmental changes autonomously. The material design may find extended utility in dental resin-restoratives, denture, and implant. As an exploratory research, the knowledge/results gained from this study will serve as preliminary data for an R01 application.

摘要：在当今的微生物组时代，人们认识到龋齿是最普遍，最昂贵的牙齿之一 全世界的慢性传染病，口腔菌群的营养不良和口腔环境引起的 改变牙齿损坏的变化。具体而言，经常摄入可发酵的碳水化合物会促进 微生物组成向酸性和耐酸物种进行了逐步转移。连续酸 - 诱导的脱矿化最终克服了唾液的缓冲能力和抗微生物特性， 导致不可逆转的牙齿破坏。这项拟议的研究的目的是发展pH响应性 能够靶向产生酸性细菌（T-TAB）和防染色的材料。我们的中心 假设是pH响应性蛋白吸附和酸增强抗菌剂（AM）的组合 效率将抑制产生酸性细菌的附着和生长，因此防止积累 致癌斑块。我们提出了三个特定的目标，以设计，开发和评估pH响应性 能够改变蛋白质吸附并实现t-tab的材料。在特定目标1中，我们将设计和 准备具有pH响应性表面特性的含有Azo-QPS的材料。 Azo-QPS化合物 在溶液中具有pH敏感的AM效率和T-TAB功能。我们将共价键入Azo-QPS功能 以单分子单层或Azo-QPS聚合物的形式进入表面，这将产生变体 AZO-QPS功能组/表面积的量。此外，通过将偶氮-QP与临床测试的AM结合 Agent，Glorhexidine（CHX），我们将增强新材料的pH响应性AM效率。在特定的目标2中， 我们将根据pH响应性可逆蛋白质吸附和 反烧开。我们将增强对地表化学与物理之间相关性的理解 属性和防污性能。具体而言，我们将关注亲水性和 电荷密度与蛋白质吸附响应于pH 4-8之间的pH变化（生物学相关） pH范围在口腔环境中。在特定目标3中，我们将评估新的现场防污和T-tab效率 模拟口腔微生物群落的多物种生物膜模型中的材料。这些将在 蔗糖的存在和不存在 - 致矿物饮食中的碳水合物。策略将需要评估生物质， 分析微生物谱并确定环境pH值。拟议的成功完成 研究将产生pH响应性的材料，这些材料是抗污染的，并根据环境响应T-TAB 自动更改。材料设计可能会在牙科树脂效果，牙医和 注入。作为一项探索性研究，这项研究从本研究中获得的知识/结果将作为初步数据 对于R01应用程序。