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.

项目摘要 存在对加速新形成的矿物的生长的试剂的未满足的需求，所述试剂具有足够的生物活性。 密度、纯度和与下面的牙冠的结合。长期目标是发展一种生物学上的 通过杠杆作用和放大自然发生的矿化作用来治疗釉质损失的灵感策略 在口腔中。因此，本申请的目的是a）优化8DSS的有效性 用于加速釉质受控矿化的肽，和B）开发控制 8DSS活动通过改变当地的口腔环境。根据研究， 研究小组强有力的初步数据是，使用生物启发的方法，8DSS肽足以 加速牙釉质的再生，具有适当的附着、结构和机械性能，和 实现临床相关性。这些研究的理由是，基于有效性和共享 钙和羟基磷灰石结合蛋白的特性，促进骨骼和牙齿的矿化。 具体地，谷氨酸-丝氨酸-丝氨酸（DSS）序列的负电荷和磷酸化重复如下： 在人类牙本质磷蛋白（DPP）中发现的磷酸化的 研究小组计划客观地检验中心假设，并通过追求 遵循两个具体目标：1）在体外测试8DSS在人牙齿上的应用，以a）再矿化 脱矿釉质和B）釉质表面的再生，和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肽加速受控矿化的有效性的初步研究 的釉质和发展战略的控制失活，或从新形成的8DSS去除 矿物质这一贡献将是重要的，因为8DSS实现仿生的机制 商业化仍不清楚，阻止临床使用的主要障碍是受控的8DSS激活 以及灭活或从新形成的组织中除去以获得低蛋白质含量和高矿物质含量 密度与健康的牙釉质一样。拟议的研究是创新的，因为它从现状出发， 通过利用和放大口腔中自然发生的矿化作用。