A biomimetic strategy to treat enamel loss

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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.