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: 10457152
• 负责人: Xuesong He
• 金额: $ 24.88万
• 依托单位: ADA FORSYTH INSTITUTE, INC.
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-07-27 至 2023-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10457152
• 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; cost; covalent bond; demineralization; density; dental resin; design; dysbiosis; environmental change; functional group; hydrophilicity; knowledge of results; lead candidate; light scattering; microbial; microbial community; microbial composition; 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.

翻译后摘要：在今天的微生物组时代，这是公认的，龋齿，最普遍和昂贵的 慢性感染性疾病是由口腔微生物群和口腔环境的生态失调引起的 导致牙齿损伤的变化。具体来说，频繁摄入可发酵碳水化合物会促进 微生物组成逐渐向产酸和耐酸物种转变。不断的酸- 诱导的脱矿作用最终克服了唾液的缓冲能力和抗微生物特性， 导致不可逆的牙齿破坏。这项研究的目标是开发pH响应的 能够靶向处理产酸细菌（t-TAB）和大肠杆菌的材料。我们的中央 假设是pH响应性蛋白质吸附和酸增强抗菌剂（AM）的结合 有效地抑制产酸菌的附着和生长，从而防止积累 致龋菌斑我们提出了三个具体的目标，设计，开发和评估pH响应 能够改变蛋白质吸附并实现t-TAB的材料。在具体目标1中，我们将设计和 制备具有pH响应性表面性质的含偶氮-QPS的材料。偶氮-QPS化合物 在溶液中具有pH敏感的AM功效和t-TAB功能。我们将共价键合Azo-QPS官能化 在一些实施方案中，将氨基以单分子单层或偶氮-QPS-聚合物的形式结合到表面上，这将产生变体QPS。 偶氮-QPS官能团的量/表面积。此外，通过将Azo-QPS与临床测试的AM结合， 试剂，洗必泰（CHX），我们将提高新材料的pH响应AM功效。在具体目标2中， 我们将评估新材料在pH响应可逆蛋白质吸附方面的性能， - 是的我们将加深对表面化学和物理之间的相互关系的理解， 性能和耐腐蚀性能。具体来说，我们将重点关注亲水性和 电荷密度与蛋白质吸附在pH 4-8之间的pH变化有关， 口腔环境中的pH值范围。在具体目标3中，我们将评估新的 材料在多物种生物膜模型，模拟口腔微生物群落。这些将在 存在和不存在蔗糖-致龋的膳食碳水化合物。战略将包括评估生物量， 分析微生物概况和确定环境pH值。成功完成拟议的 研究将产生pH响应性材料，这些材料是可降解的，并获得t-TAB以响应环境 自主变化。该材料的设计可在牙科树脂、义齿和 植入作为一项探索性研究，本研究获得的知识/结果将作为初步数据 R 01应用程序