Enamel biomimetics—fiction or future of dentistry

Tooth enamel is a complex mineralized tissue consisting of long and parallel apatite crystals configured into decussating enamel rods. In recent years, multiple approaches have been introduced to generate or regenerate this highly attractive biomaterial characterized by great mechanical strength paired with relative resilience and tissue compatibility. In the present review, we discuss five pathways toward enamel tissue engineering, (i) enamel synthesis using physico-chemical means, (ii) protein matrix-guided enamel crystal growth, (iii) enamel surface remineralization, (iv) cell-based enamel engineering, and (v) biological enamel regeneration based on de novo induction of tooth morphogenesis. So far, physical synthesis approaches using extreme environmental conditions such as pH, heat and pressure have resulted in the formation of enamel-like crystal assemblies. Biochemical methods relying on enamel proteins as templating matrices have aided the growth of elongated calcium phosphate crystals. To illustrate the validity of this biochemical approach we have successfully grown enamel-like apatite crystals organized into decussating enamel rods using an organic enamel protein matrix. Other studies reviewed here have employed amelogenin-derived peptides or self-assembling dendrimers to re-mineralize mineral-depleted white lesions on tooth surfaces. So far, cell-based enamel tissue engineering has been hampered by the limitations of presently existing ameloblast cell lines. Going forward, these limitations may be overcome by new cell culture technologies. Finally, whole-tooth regeneration through reactivation of the signaling pathways triggered during natural enamel development represents a biological avenue toward faithful enamel regeneration. In the present review we have summarized the state of the art in enamel tissue engineering and provided novel insights into future opportunities to regenerate this arguably most fascinating of all dental tissues. Five pathways for tooth enamel engineering hold great promise for developing new technologies, leading to novel biomaterials and biotechnologies to regenerate enamel tissue. Tooth enamel is a unique tissue-specific biomaterial with exceptional structural and mechanical properties. In recent years, many approaches have been adopted to generate or regenerate this complex tissue; Mirali Pandya and Thomas Diekwisch of Texas A&M College of Dentistry, USA conducted a review of the current state and future directions of enamel tissue engineering. In their review, the authors focused on five pathways for enamel tissue engineering: (1) physical synthesis of enamel; (2) biochemical enamel engineering; (3) in situ enamel engineering; (4) cell-based enamel engineering; and (5) whole tooth regeneration. The authors conclude that those five approaches will help identify the biological mechanisms that lead to the generation of tooth enamel.