pH-sensitive materials responding to metabolic activities of cariogenic plaque

摘要：在当今的微生物时代，众所周知，龋病是最普遍和最昂贵的疾病之一 世界范围内的慢性传染病，由口腔微生物区系和口腔环境的失调引起 导致牙齿损伤的变化。具体地说，经常摄入可发酵的碳水化合物会促进 微生物组成逐渐向产酸和耐酸物种转移。连续不断的酸- 诱导脱矿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标是开发对pH敏感的 能够靶向处理产酸菌(t-TAB)和防污的材料。我们的中央 假说是pH响应蛋白吸附和酸增强抗菌剂(AM)的结合 药效会抑制产酸细菌的附着和生长，从而防止积聚。 导致龋齿的斑块。我们提出了三个具体目标来设计、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。在具体目标1中，我们将设计和 制备具有pH响应性表面性能的偶氮QPS材料。偶氮-QPS化合物 在溶液中具有pH敏感的AM药效和t-TAB功能。偶氮-QPS官能团的共价键合 以单分子单分子膜或偶氮QPS聚合物的形式在表面上基团，这将产生不同的 偶氮-QPS官能团的量/比表面积。此外，通过将偶氮-QPS与临床测试的AM结合 洗必泰(CHX)，我们将提高新材料的pH响应性AM的功效。在具体目标2中， 我们将从pH响应性的可逆蛋白质吸附和 防污。我们将加强对表面化学和物理之间的关系的理解 性能和防污性能。具体地说，我们将重点讨论亲水性和亲水性之间的关系 电荷密度与蛋白质吸附对pH在4-8之间变化的响应，与生物相关 口腔环境中的PH值范围。在具体目标3中，我们将评估现场防污和t-TAB的效果 材料在模拟口腔微生物群落的多物种生物膜模型中。这些操作将在 蔗糖--致龋性膳食碳水化合物的存在和缺失。战略将需要评估生物量， 分析微生物谱并测定环境pH值。圆满完成拟议中的 研究将产生pH响应材料，这种材料是防污的，并获得t-TAB，以响应环境 会自动发生变化。这种材料设计可能会在牙科树脂-修复体、义齿和 植入。作为探索性研究，本研究所获得的知识/结果将作为初步数据 适用于R01应用程序。

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.