Microenvironmental characterization and manipulation to prevent secondary caries

预防继发龋的微环境特征和操作

• 批准号: 10814030
• 负责人: Dipankar Koley
• 金额: $ 54.24万
• 依托单位: OREGON STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-07-05 至 2025-07-04
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10814030
• 关键词: Address; Adhesions; Adopted; AlamarBlue; Attention; Bacteria; Behavior; Biological; Biological Assay; Buffers; Cells; Chemicals; Clinical; Complex; Composite Resins; Confocal Microscopy; Coupled; Data; Dental; Dental Materials; Dental Plaque; Dental Pulp; Dental caries; Development; Devices; Diffusion; Effectiveness; Environment; Excision; Exposure to; Failure; Filler; Formulation; Foundations; Future; Glass; Growth; Hardness; Health; Human; Hydrogen Peroxide; In Vitro; Ions; Kinetics; Lactic acid; Life; Longevity; Measurable; Measurement; Measures; Metabolic; Metals; Microbial Biofilms; Microscopic; Microscopy; Modeling; Nutrient; Oral cavity; Oregon; Performance; Persons; Plant Resins; Population; Predisposition; Recurrence; Reproducibility; Research; Resolution; Root Caries; Saliva; Scanning; Science; Services; Specimen; Surface; Techniques; Testing; Time; Tooth Demineralization; Tooth structure; Undifferentiated; United States National Institutes of Health; Universities; Width; antimicrobial; biomaterial compatibility; clinically relevant; composite restoration; cytotoxicity; design; divalent metal; effectiveness evaluation; effectiveness testing; electric impedance; fundamental research; human subject; improved; in vitro Model; in vivo; in vivo evaluation; innovation; interfacial; meter; microbial; microbial colonization; microbiome; microbiome alteration; microsensor; novel; oral biofilm; oral microbiome; organic acid; polymicrobial biofilm; prevent; restoration; restorative dentistry; restorative material; sensor; volunteer

A common reason cited for dental composite replacement is the recurrence of caries around existing restorations due to microbial activity. Treatment typically involves the removal of decayed tooth structure and placement of a new restoration. Since the microbial environment remains the same, the new tooth-restoration complex may also be susceptible to failure. Thus, the problem is not adequately addressed in current dental treatment approaches. More innovative materials are required that can purposefully bias the microbial environment toward improved health. Our preliminary data demonstrate that Mg2+ or Zn2+ released from bioactive glass (BAG)-containing resin composites can support a healthy microbial environment, thus directly addressing the root of the caries problem. Here we propose a new strategy involving Mg2+-and Zn2+-releasing dental composites that can favorably alter the microbiome on and around dental restorations such that the local pH >5.5. AIM 1: Optimize Mg2+- and Zn2+-releasing bioactive glass (BAG)-containing dental composites for long-term support of a healthy oral microbiome. Scanning electrochemical microscopy (SECM) will be used to optimize pH dependent Mg2+ and Zn2+ release kinetics from different Mg- and Zn-BAG formulations. Later, dental plaque derived multi species biofilm growth rate, volume, species composition and pH at the BAG surface will be quantified and optimized such that local pH > 5.5. AIM 2: Test the effectiveness of new Mg-BAG and Zn-BAG composites in an in vitro secondary caries model. Placement of a restoration has the inherent challenge of gap formation between the dental material and the tooth structure. Currently, little information is available on how bacteria behave in microgaps. For example, microbial colonization, diffusion rates, and organic acid metabolites may be very different within gaps as compared to exposed surfaces in the oral cavity, potentially leading to enhanced tooth decay at the interface. Here we will develop an in vitro microgap model using the electrochemical sensors techniques to measure the biological activity and the effect on the microbial population in these microenvironments such that local pH > 5.5. AIM 3: In vivo evaluation of Mg-BAG and Zn-BAG composites with intraoral appliances. The cytotoxicity of Mg-BAG and Zn-BAG will be tested using undifferentiated dental pulp cells compared to standard dental composites. The in vitro optimized Mg-BAG and Zn-BAG composites that are shown to have equal or lower cytotoxicity than typical composite will be placed in intraoral appliances to be tested in volunteers. This real-life scenario will evaluate the effectiveness of the composites when all biologically relevant parameters are present that potentially interfere with the performance of Mg-BAG and Zn-BAG composites. This will also provide a direct comparison between the in vitro model and the clinical situation. Our proposal will lay the foundation for further metal ions driven research on biofilm growth and behavior, as well as for the development of a more realistic in vitro secondary caries model that includes chemical microenvironments created by differential biofilm metabolic activities within microscopic gaps.

一个常见的原因引用的牙科复合材料更换是复发的龋齿周围现有的牙列 由于微生物的活动。治疗通常包括去除蛀牙结构和放置一个 新的恢复。由于微生物环境保持不变，新的牙齿修复复合物也可能 容易失败。因此，该问题在当前的牙科治疗方法中没有得到充分解决。 需要更多的创新材料，这些材料可以有目的地使微生物环境偏向于改善 健康我们的初步数据表明，Mg ~（2+）或Zn ~（2+）从生物活性玻璃（BAG）树脂中释放出来， 复合材料可以支持健康的微生物环境，从而直接解决龋齿问题的根源。 在这里，我们提出了一种新的策略，涉及Mg 2+和Zn 2+释放牙科复合材料，可以有利地改变 在牙齿周围的微生物组，使局部pH >5.5。 目的1：优化含Mg 2+和Zn 2+释放生物活性玻璃（BAG）的牙科复合材料， 支持健康的口腔微生物组。将使用扫描电化学显微镜（SECM）优化pH值 不同Mg-和Zn-BAG制剂的依赖性Mg 2+和Zn 2+释放动力学。后来，牙菌斑 在BAG表面的衍生的多物种生物膜生长速率、体积、物种组成和pH将是 定量并优化，使得局部pH > 5.5。目的2：测试新的Mg-BAG和Zn-BAG的有效性 复合材料在体外继发性龋齿模型中的作用。修复体的放置具有间隙的固有挑战 在牙齿材料和牙齿结构之间的形成。目前，关于如何做到这一点， 细菌在微间隙中活动。例如，微生物定植、扩散速率和有机酸代谢产物 与口腔中的暴露表面相比， 界面处的蛀牙加剧。在这里，我们将开发一个体外微间隙模型，使用电化学 传感器技术来测量生物活性和对这些微生物种群的影响， 微环境，使局部pH > 5.5。目的3：体内评价Mg-BAG和Zn-BAG复合材料， 口内器具将使用未分化的牙髓测试Mg-BAG和Zn-BAG的细胞毒性 与标准牙科复合材料相比。体外优化的Mg-BAG和Zn-BAG复合材料， 具有与典型复合材料相同或更低的细胞毒性的复合材料将被放置在口内器具中， 在志愿者中测试。这个真实的场景将评估复合材料的有效性， 存在可能干扰Mg-BAG和Zn-BAG性能的相关参数 复合材料.这也将提供体外模型和临床情况之间的直接比较。 我们的建议将奠定基础，进一步金属离子驱动的生物膜生长和行为的研究，以及 至于开发一种更真实的体外继发性龋齿模型， 微环境由微间隙内的差异生物膜代谢活动产生。