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The development of human enamel involves a complex series of events including the secretion and degradation of a unique extracellular matrix. Ameloblasts progress through a succession of cellular phenotypes executing specialized secretory and regulatory functions. When performing optimally, ameloblasts produce a highly structured and mineralized tissue. Given the elaborate developmental events required for normal enamel formation, it is not surprising that a variety of enamel malformations arise from defects in matrix synthesis, secretion and extracellular processing. Normal matrix secretion and post-secretory processing by ameloblasts can be affected by a variety of hereditary and environmental conditions. These disturbances can result in an abnormal amount and/or composition of matrix proteins, and subsequently, an altered enamel structure and/or mineral content. For example, abnormal matrix removal during enamel maturation apparently contributes to hypomineralization associated with dental fluorosis. Incomplete matrix removal can also occur in several different forms of the hereditary condition amelogenesis imperfects. Specific types of this condition can have retention of substantial enamel protein (e.g. 5% by weight) that is, at least in part, composed of amelogenin and/or its breakdown products. Characterization of the enamel proteins in teeth affected by developmental disturbances can provide insight into the pathogenesis and normal formation of this highly specialized tissue.

The amelogenins of developing dental enamel are tissue-specific proteins, rich in proline, leucine, histidine and glutamyl residues, and synthesized by the ameloblast cells of the inner enamel epithelium. These proteins comprise the bulk of the extracellular matrix that becomes mineralized with a hydroxyapatite phase to become the mature enamel. Examination of the amino acid sequences of amelogenins from a range of mammals shows a high degree of evolutionary sequence conservation, suggestive of specialized function. Recently it has been shown that multiple amelogenin components, observed in the matrix, arise both by a sequence of post-secretory proteolytic processing and by the expression of alternatively spliced mRNAs generated from the amelogenin gene(s) that are located on the sex chromosomes. Although the function of these amelogenins in enamel biomineralization is unknown, physico-chemical studies of recombinant amelogenins have shown that they undergo a self-assembly process in vitro generating supra-molecular 'nanosphere' structures, and recent observations in vivo point to a functional role for the nanospheres in the ultrastructural organization of the secretory enamel matrix, conducive to the organized development of the earliest mineral crystallites.

Secretory ameloblasts have multiple functions including the synthesis and resorption of enamel matrix proteins and calcium transport during enamel formation. We have examined these functions by means of cytochemistry and immunocytochemistry. Enamel proteins, amelogenins and enamelins are localized in the biosynthetic pathways of ameloblasts and in the forming enamel. Sulfated glycoconjugates are present in secretory ameloblasts. The distal junctional complex of ameloblasts may act as a permeability barrier to enamel proteins, thereby confining the secreted proteins to the growing enamel front. Secretory ameloblasts contain lysosomal enzymes in the Golgi lysosome endoplasmic reticulum system and also exhibit absorptive capacity, which might be associated with an early decrease in extracellularly degraded enamel proteins. Active calcium transport through the ameloblasts towards the growing enamel is indicated by the demonstration of Ca-ATPase activity along the plasma membranes. A calcium-dependent modulator protein, calmodulin, is localized in ameloblasts, suggesting that early enamel mineralization is dependent upon calmodulin-regulated Ca-ATPase in ameloblasts. These results suggest that the secretory ameloblast is a highly specialized multifunctional cell in the production, resorption and degradation of enamel matrix and in the active calcium transport essential for matrix mineralization during enamel formation.

The formation of enamel takes place through a sequence of processes that can be mimicked in inorganic materials chemistry. This chapter describes the generic features of enamel biomineralization in terms of a house-building analogy. Four stages are identified: supramolecular preorganization and spatial patterning; interfacial molecular recognition in inorganic nucleation; vectorial crystallization; and pattern evolution and hierarchy. Each of these concepts can be translated into synthetic approaches to the formation of inorganic materials with organized architectures. An example of applying this biomimetic paradigm is described. Supersaturated water-in-oil microemulsions have been used to synthesize microskeletal calcium phosphates by controlled nucleation and vectorial growth in constrained reaction environments. The results of these preliminary studies suggest that biomimetic concepts could be useful in the fabrication of biomaterial implants with controlled porosity and microstructure.