The Growth Mechanisms and Biomimetics of Tooth Enamel*

A very fundamental part of biomineralization is the complex extracellular macromolecular framework in which mineralization occurs, such as the collagen fibrils in bone and dentin, polysaccharides in nacre and amelogenin and non-amelogenin proteins in dental enamel. Unlike other mineralized tissues, such as bone and dentin, mature enamel is acellular and cannot regenerate itself after substantial mineral loss. Biomimetic enamel regrowth is a significant topic in material science and dentistry as an alternative approach for the treatment of defects in dental enamel. We have developed protocols for superficial biomimetic enamel regrowth, based on a novel amelogenin-chitosan hydrogel. Amelogenin is a critical protein for controlling the organized growth of apatite crystals in enamel. We expanded upon the concept of biomineralization to design smaller amelogenin-inspired peptides with conserved functional domains for clinical translation. The synthetic peptides displayed a characteristic nanostructured scaffold reminiscent of ‘nanospheres’ seen in the enamel matrix and effectively controlled apatite nucleation in vitro. Following application of the peptides to sectioned human molar teeth, a robust, oriented, synthetic aprismatic enamel was observed in situ. There was a two-fold increase in the hardness and modulus of the regrown enamel-like apatite layers and an increase in the attachment of the tooth-regrown layer interface compared to control samples. Repeated peptide applications generated multiple enamel-like HAP layers of limited thickness produced by epitaxial growth in which c-axis oriented nanorods evolved on the surface of native enamel. We report that peptide analogues with active domains can effectively regulate the orientation of regenerated HAP layers to influence functional response.