Manipulation of Bacterial Metabolism: A New Approach to Develop Smart Dental Composites

操纵细菌代谢：开发智能牙科复合材料的新方法

• 批准号: 9580833
• 负责人: Dipankar Koley
• 金额: $ 44.55万
• 依托单位: OREGON STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-08-01 至 2023-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9580833
• 关键词: Acids; Affect; Animal Model; Artificial Saliva; Bacteria; Biocompatible Materials; Calcium; Caliber; Chemicals; Complement; Dental; Dental Materials; Dental Plaque; Dental caries; Dentistry; Development; Encapsulated; Engineering; Environment; Formulation; Gene Expression Profiling; Growth; Health; Height; Human; Hydrogels; Hydrogen Peroxide; Immobilization; Ions; Knowledge; Lactic acid; Lesion; Longevity; Measurement; Measures; Metabolic; Metabolism; Metals; Microbial Biofilms; Microscope; Microscopy; Mission; Modeling; Monitor; Nutrient; Oral cavity; Organism; Particle Size; Plant Resins; Play; Production; Reproducibility; Research; Role; Sampling; Scanning; Streptococcus gordonii; Streptococcus mutans; Surface; Techniques; Testing; Time; Tooth Demineralization; Tooth structure; United States National Institutes of Health; Veillonella parvula; adaptive learning; bacterial metabolism; base; biomaterial compatibility; composite restoration; demineralization; design; experimental study; flexibility; innovation; microbial; microsensor; next generation; novel; novel strategies; oral biofilm; prevent; restoration; sensor; temporal measurement; tooth filling; transcriptome

Proposal Summary In the oral cavity, metabolic lactic acid production by bacteria and the associated change in pH are suspected to play a key role in the longevity and integrity of dental composite restorations. We propose gathering fundamental knowledge about the chemical microenvironment created by bacterial metabolites at the dental material interface to design next-generation dental composites. Our central hypothesis is that metal ion (Ca2+, Mg2+)-releasing composites can be engineered to influence bacterial metabolism and manipulate the chemical microenvironment to inhibit tooth demineralization. To quantify these bacterial chemical microenvironments, we will apply our newly developed unique electrochemical sensors (pH, lactate, H2O2, metal ions) to measure major bacterial metabolites such as lactate and H2O2 in real time. Aim 1: Determine the effects of metal ions on bacterial metabolism and the chemical microenvironment. We will determine the effects of metal ions on bacterial metabolism with dental plaque-derived microcosm biofilms such that the local pH is 5.5 or higher. To create a genetically amendable and reproducible biofilm model, we will extend our study to replicate local pH, lactate, and H2O2 concentrations with different ratios of three model organisms: Streptococcus mutans (lactate producing, pH lowering), Veillonella parvula (lactate consuming), and Streptococcus gordonii (H2O2 producing). We will use pH, lactate, and H2O2 microsensors as scanning electrochemical microscope (SECM) probes to determine the local rate of lactate and H2O2 production and the corresponding local pH change above the biofilms in real time in the presence of metal ions. Aim 2: Quantify the local pH above the bacterial biofilms grown on metal ion-releasing BAG composites. We will use SECM to measure pH at 20 µm above the dental plaque microcosm and above three-species biofilm (Sm/Sg/Vp) grown on different metal ion-releasing composites (similar concentration ranges as in Aim 1). This will help us determine whether metal ions released from BAG composites can influence bacterial metabolism such that the local pH is >5.5. We will also use Ca2+- and Mg2+-sensing SECM probes to quantify the local concentration of metal ions released from BAG composites to determine the ion concentration to which bacteria will be exposed while growing on these composites. Aim 3: Measure pH and H2O2 at the biofilm–composite interface in real time. Innovative flexible wire sensors (pH, H2O2, metal ions) will be placed at the highly dynamic material–biofilm interface to monitor it and answer a crucial question: How do bacterial metabolites influence biomaterial integrity and how do metal ions released from biomaterials affect bacterial metabolites? The proposed research provides a significant step towards identifying next-generation “smart” dental composites that can control biofilm composition to maintain a local pH of 5.5 or higher, thus inhibiting adjacent tooth demineralization and extending the lifespan of dental composite restorations.

提案摘要 在口腔中，可疑由细菌和pH中相关的变化产生代谢乳酸 在牙科复合修复体的寿命和完整性中发挥关键作用。我们建议聚会 关于细菌代谢产生的化学微环境的基本知识 设计下一代牙科复合材料的材料界面。我们的中心假设是金属离子（Ca2+， MG2+） - 可以设计释放复合材料以影响细菌代谢并操纵化学物质 微环境抑制牙齿去矿化。为了量化这些细菌化学微环境，我们 将应用我们新开发的独特电化学传感器（pH，鞋底，H2O2，金属离子）测量 主要的细菌代谢产物，例如鞋底和H2O2。目标1：确定金属离子对 细菌代谢和化学微环境。我们将确定金属离子对 细菌代谢与牙菌斑衍生的微观膜生物膜，使得局部pH值为5.5或更高。到 创建一个普遍的修正和可复制的生物膜模型，我们将扩展研究以复制本地pH， 乳酸和H2O2浓度的三种模型生物的比例不同：链球菌突变（乳酸菌链球菌） 产生，pH降低），Veillonella parvula（乳酸消耗）和Gordonii链球菌（H2O2产生）。 我们将使用pH，乳酸和H2O2微传感器作为扫描电化学显微镜（SECM）问题 确定验证液的局部速率和H2O2产生的速率，以及相应的局部pH变化 在金属离子存在下实时生物膜。目标2：量化细菌生物膜上方的局部pH 在金属离子释放袋构成上生长。我们将使用SECM在牙齿上方20 µm处测量pH值 斑块缩影和以上生物膜（SM/SG/VP）在不同金属释放上生长的生物膜（SM/SG/VP） 组成（类似的浓度范围与AIM 1中的浓度范围）。这将帮助我们确定金属离子是否释放 从袋子组成中可以影响细菌代谢，使得局部pH> 5.5。我们还将使用Ca2+ - 和mg2+ - 传感secm问题，以量化从袋中释放的金属离子的局部浓度 复合材料以确定在生长时将暴露于细菌的离子浓度 复合材料。 AIM 3：测量生物膜 - 合并界面的pH和H2O2实时。创新的灵活性 电线传感器（pH，H2O2，金属离子）将放置在高度动态的材料 - biofilm接口上，以监视它 并回答一个关键问题：细菌代谢产物如何影响生物材料完整性以及金属如何 从生物材料释放的离子会影响细菌代谢产物？拟议的研究提供了重要的一步 旨在确定可以控制生物膜组成以维护的下一代“智能”牙科组成 局部pH值为5.5或更高，从而抑制邻近的牙齿去矿化并延长牙齿的寿命 复合修复体。