A biomimetic strategy to treat enamel loss

治疗牙釉质缺失的仿生策略

• 批准号: 10042609
• 负责人: Felicitas B Bidlack
• 金额: $ 29.85万
• 依托单位: ADA FORSYTH INSTITUTE, INC.
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-09-09 至 2022-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10042609
• 关键词: Acids; Address; Adult; Alanine; Aspartate; Binding; Binding Proteins; Biological; Biomimetics; Calcium; Calcium Binding; Cells; Characteristics; Charge; Chemicals; Child; Clinical; Computer Models; Crystallization; DSPP gene; Data; Defect; Dental Enamel; Dental caries; Dentin; Dentistry; Deposition; Development; Diffusion; Durapatite; Effectiveness; Electron Microscopy; Environment; Enzymes; Equilibrium; Excision; Goals; Growth; Human; Hydroxyapatites; In Vitro; Ionic Strengths; Ions; Kinetics; Legal patent; Length; Lesion; Liquid substance; Measures; Mechanics; Minerals; Modification; Monitor; Natural regeneration; Oral; Oral cavity; Peptides; Phase; Phosphorylation; Proteins; Public Health; Research; Research Personnel; Resolution; Serine; Structure; Surface; Techniques; Testing; Tissues; Titrations; Tooth Crowns; Tooth Remineralization; Tooth structure; Variant; White Spots; base; bone; calcium phosphate; carboxylate; chemical stability; clinically relevant; demineralization; density; experimental study; falls; in vitro testing; innovation; inorganic phosphate; light microscopy; mechanical properties; microCT; mineralization; multidisciplinary; organizational structure; prevent; remineralization; self assembly; tissue repair

PROJECT SUMMARY There is an unmet need for an agent that accelerates the growth of newly formed mineral with sufficient density, purity, and bonding to the underlying tooth crown. The long-term goal is to develop a biologically inspired strategy to treat enamel loss through leveraging and amplifying the naturally occurring mineralization in the oral cavity. The objective in this application, therefore, is to a) optimize the effectiveness of the 8DSS peptide for accelerating controlled mineralization of enamel and b) to develop strategies for the control of 8DSS activity by modification of the local oral environment. The central hypothesis, based on the research team's strong preliminary data, is that using a biologically inspired approach, 8DSS peptide sufficiently accelerates the regeneration of enamel with appropriate attachment, structure and mechanical properties, and achieves clinical relevance. The rationale for these studies is that based on the effectiveness and shared characteristics of calcium and hydroxyapatite-binding proteins that facilitate mineralization in bone and teeth. Specifically, the negative charge and phosphorylation of aspartate-serine-serine (DSS) sequence repeats as seen in human dentin phosphoprotein (DPP) is known to promote the formation of hydroxyapatite. The research team plans to objectively test the central hypothesis and achieve the objective by pursuing the following two Specific Aims: 1) Test in vitro 8DSS application on human teeth for a) remineralization of demineralized enamel and b) regeneration of enamel surfaces, and 2) Test in vitro that 8DSS activity can be controlled by variations in local conditions. The contribution here is expected to be an expansion of our preliminary studies to enhance the effectiveness of the 8DSS peptide for accelerating controlled mineralization of enamel and develop strategies for the controlled inactivation, or removal of 8DSS from newly formed mineral. This contribution will be significant because the mechanism of 8DSS achieving biomimetic remineralization remains unclear and the major hurdle preventing clinical use is the controlled 8DSS activation and deactivation, or removal from the newly formed tissue to achieve the low protein content and high mineral density as in healthy enamel. The proposed research is innovative, because as it departs from the status quo by leveraging and amplifying the naturally occurring mineralization in the oral cavity.

项目概要 对于一种能够以足够的速度加速新形成的矿物生长的试剂的需求尚未得到满足。 密度、纯度以及与底层牙冠的粘合。长期目标是开发一种生物 通过利用和放大自然发生的矿化来治疗牙釉质损失的启发性策略 在口腔中。因此，本应用的目标是 a) 优化 8DSS 的有效性 b) 开发控制牙釉质矿化的策略 8DSS 通过改变局部口腔环境来发挥作用。基于研究的中心假设 团队强有力的初步数据是，使用生物学启发的方法，8DSS 肽足以 加速牙釉质的再生，具有适当的附着力、结构和机械性能，并且 达到临床相关性。这些研究的基本原理是基于有效性和共享性 促进骨骼和牙齿矿化的钙和羟基磷灰石结合蛋白的特性。 具体来说，天冬氨酸-丝氨酸-丝氨酸 (DSS) 序列的负电荷和磷酸化重复如下 人类牙本质磷蛋白 (DPP) 已知可促进羟基磷灰石的形成。这 研究团队计划客观地检验中心假设并通过追求来实现目标 以下两个具体目标： 1) 体外测试 8DSS 在人类牙齿上的应用，以实现 a) 的再矿化 脱矿牙釉质和 b) 牙釉质表面再生，以及 2) 体外测试 8DSS 活性可以 受当地条件变化的控制。这里的贡献预计将是我们的扩展 增强 8DSS 肽加速受控矿化效果的初步研究 牙釉质并制定控制失活的策略，或从新形成的牙釉质中去除 8DSS 矿物。这一贡献将是意义重大的，因为 8DSS 实现仿生的机制 再矿化仍不清楚，阻碍临床使用的主要障碍是受控的 8DSS 激活 和失活，或从新形成的组织中去除，以实现低蛋白质含量和高矿物质含量 密度与健康牙釉质相同。拟议的研究具有创新性，因为它脱离了现状 通过利用和放大口腔中自然发生的矿化作用。