The goal of this exploratory/developmental research proposal is to explore a novel biomimetic calcium phosphate (CaP) composite material that will have an enamel-like structure and can be applied to restore posterior Class I cavities. Such an enamel-like biocomposite will integrate with the natural dental tissues through a strong chemical bond, and restore the tooth structures. It is based on the synthesis of a layered chitosan-monetite composite that can transform into an organized hydroxyapatite composite with improved mechanical properties. We demonstrated that that our newly designed amelogenin-inspired peptide P26 can promote regrowth of an enamel layer integrated with natural enamel and dentin. Building on these findings, we propose to apply the peptides to the monetite system in order to regulate the organized growth of apatite crystals at restoration-tooth interface. We hypothesize that i) organized enamel-like apatite crystals will be formed through a phase transformation of layered chitosan-monetite composite in the presence of amelogenin- inspired peptide ; and ii) the peptide will promote and control the in situ growth of organized apatite crystals at the enamel/dentin surface to integrate the biocomposite with tooth structures. We plan to test our hypotheses and approach the goal by pursuing the following three specific aims.
Aim I) To synthesize a biomimetic chitosan-CaP composite with organized structure through a monetite-to-apatite phase transformation and to optimize its microstructure, biomechanical properties and setting time by incorporating an amelogenin-inspired peptide P26 and by examining the effects of additives such as Ca, phosphate, alkaline and amorphous calcium phosphate (ACP) on the abovementioned parameters. We hypothesize that incorporation of the small active peptides will assist in controlling the nanostructure of the final product and hence improve its hardness and elastic modulus. We will examine the release kinetics of mineralizing ions and P26 from the biocomposite material.
Aim II) To evaluate integration of the biocomposite developed in Aim I to dental enamel and dentin using human extracted 3rd molar slabs. We will examine the interface between the biomimetic restorative material and the underlying tooth structures. We hypothesize that a strong chemical bond interface will be formed as the result of active peptide-guided remineralization at the tooth-restoration interface. If successful, this study will lead to an alternative dental restorative material to treat posterior Class I cavities, that has physical and chemical properties close to dental tissues (enamel/dentin), integrates well with the underlying tissues, and exhibits an extended longevity superior to the current restorative materials.
We propose to synthesize a biomimetic calcium phosphate (CaP) composite material that will have an enamel- like structure and can be applied to restore posterior Class I cavities. Such an enamel-like biocomposite will integrate with the natural dental tissues through a strong chemical bond, will exhibit an extended longevity superior to the current restorative materials, and will restore the tooth structures. Ex vivo studies and preclinical efficacy tests will be subject of a future R01 proposal.
