Role of macromolecular assembly of enamel matrix proteins in enamel formation.

Unlike other mineralized tissues, mature dental enamel is primarily (> 95% by weight) composed of apatitic crystals and has a unique hierarchical structure. Due to its high mineral content and organized structure, enamel has exceptional functional properties and is the hardest substance in the human body. Enamel formation (amelogenesis) is the result of highly orchestrated extracellular processes that regulate the nucleation, growth, and organization of forming mineral crystals. However, major aspects of the mechanism of enamel formation are not well-understood, although substantial evidence suggests that protein-protein and protein-mineral interactions play crucial roles in this process. The purpose of this review is a critical evaluation of the present state of knowledge regarding the potential role of the assembly of enamel matrix proteins in the regulation of crystal growth and the structural organization of the resulting enamel tissue. This review primarily focuses on the structure and function of amelogenin, the predominant enamel matrix protein. This review also provides a brief description of novel in vitro approaches that have used synthetic macromolecules (i.e., surfactants and polymers) to regulate the formation of hierarchical inorganic (composite) structures in a fashion analogous to that believed to take place in biological systems, such as enamel. Accordingly, this review illustrates the potential for developing bio-inspired approaches to mineralized tissue repair and regeneration. In conclusion, the authors present a hypothesis, based on the evidence presented, that the full-length amelogenin uniquely regulates proper enamel formation through a process of cooperative mineralization, and not as a pre-formed matrix.