Thursday, November 21, 2024
11/21/2024
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.
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