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A biomimetic strategy to treat enamel loss

治疗牙釉质缺失的仿生策略

基本信息

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
项目类别：
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

项目摘要

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