Enamel biomimetics—fiction or future of dentistry

Abstract

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.

Effect of self-assembling peptide P11-4 on orthodontic treatment-induced carious lesions

“…The greater difference between test and control lesions, however, occurred in the impedance values compared with that in the morphometric measurements, thereby confirming that SAP P 11 -4 acts predominantly by regenerating the mineral structure of the enamel of the lesion body and not just the surface 23,24 . Moreover, at the last study visit at day 180, the impedance values for test lesions indicated regression of caries into very outer enamel, whereas the impedance values for the control lesions indicated still caries throughout the whole enamel layer 31,33 , which agrees with previous data that fluoride (in the present study as fluoride-based professional prophylaxis paste and home care toothpaste) only acts in the top 30-50 µm of the enamel surface 13,14,34 .…”

Tissue Engineering Approaches for Enamel, Dentin, and Pulp Regeneration: An Update

“…Enamel, the hardest tissue in the human body, is a highly organized dental tissue, covering the outer layer of the tooth crown. It possesses unique mechanical and structural properties [29][30][31][32], relying on its high hydroxyapatite content, the arrangement of apatite crystals into enamel prisms, and finally, the alignment of these prisms in a picket-fence appearance in a tissue of high physical resilience and great hardness [33][34][35][36][37]. Ameloblasts, the enamel-forming cells, are specialized epithelial cells differentiating from the inner cells of the enamel organ [38].…”

“…Finally, they undergo apoptosis and the mature enamel becomes acellular. As a result, once damaged, unlike other biomineralized hard tissues such as dentin and bone, the enamel cannot regenerate by itself [37,46]. Therefore, a reparative healing of destroyed enamel depends mainly, if at all, on acellular remineralization of superficial demineralized defects [47].…”

“…Despite the urgent need for tooth enamel regeneration, enamel tissue engineering is facing many difficulties [50][51][52][53], including the complex posttranslational protein modifications required for crystal growth [54] and the recapitulation of the unique movements of ameloblasts during the organization of hydroxyapatite crystals into the enamel prisms [55]. Despite all these trials and findings, to date, there exists no scheme for viable cellbased in vivo enamel tissue engineering [37]. The main challenge remains to produce an artificial enamel that resembles the prismatic and interprismatic patterns of natural enamel, [57], induced pluripotent stem cells (iPSCs) [58], and human keratinocyte stem cells (hKSCs) [59,60] were suggested to differentiate into enamel-forming ameloblasts when combined with mouse or human embryonic dental mesenchyme.…”

Identification of Key Functional Motifs of Native Amelogenin Protein for Dental Enamel Remineralisation

“…However, biomimetic in vitro strategies employing proteins which contribute to the EMP layer such as native amelogenin and leucine-rich amelogenin peptide (LRAP) have demonstrated the ability to bind hydroxyapatite crystals, which is crucial for remineralisation. The use of LRAP in vitro has demonstrated the de novo formation of HA [ 19 ]. This is of significant importance to researchers and dental clinicians to develop biomimetic peptides as potential treatments to initiate remineralisation.…”