A biomimetic strategy to treat enamel loss

治疗牙釉质缺失的仿生策略

• 批准号: 10259677
• 负责人: Felicitas B Bidlack
• 金额: $ 24.88万
• 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 2023-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10259677
• 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.

项目总结 对一种能够加速新形成的矿物生长的试剂的需求还没有得到满足，这种矿物具有足够的 密度、纯度和与底层牙冠的粘合力。长期目标是发展出一种生物学上的 通过利用和放大自然矿化来治疗釉质流失的创新策略 在口腔里。因此，该应用程序的目标是a)优化8DSS的有效性 促进牙釉质受控矿化的多肽和b)制定控制牙釉质矿化的策略 8DSS活性可通过改变局部口腔环境来实现。基于这项研究的中心假设 团队强有力的初步数据是，使用生物启发的方法，8DSS多肽足够 通过适当的附着性、结构和机械性能加速牙釉质的再生 达到临床应用的目的。这些研究的基本原理是基于有效性和共享 促进骨骼和牙齿矿化的钙和羟基磷灰石结合蛋白的特征。 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 在人牙本质中发现的磷蛋白(DPP)被认为可以促进羟基磷灰石的形成。这个 研究小组计划客观地检验中心假说，并通过追求 以下两个具体目标：1)在体外测试8DSS在人类牙齿上的应用a)再矿化 脱矿牙釉质和b)牙釉质表面的再生，以及2)体外测试8DSS活性可以 受当地条件变化的控制。预计这里的贡献将是我们的扩展 提高8DSS多肽促进控矿效果的初步研究 并制定策略，控制新形成的牙釉质中8DSS的失活或去除 矿物。这一贡献将是重大的，因为8DSS实现仿生的机制 再矿化尚不清楚，阻碍临床应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移除，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。这项拟议的研究具有创新性，因为它偏离了现状 通过利用和放大口腔中自然发生的矿化作用。