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Journal of Dental Research Sep 2021Biomineralization of enamel, dentin, and bone involves the deposition of apatite mineral crystals within an organic matrix. Bone and teeth are classic examples of... (Review)
Review
Biomineralization of enamel, dentin, and bone involves the deposition of apatite mineral crystals within an organic matrix. Bone and teeth are classic examples of biomaterials with unique biomechanical properties that are crucial to their function. The collagen-based apatite mineralization and the important function of noncollagenous proteins are similar in dentin and bone; however, enamel is formed in a unique amelogenin-containing protein matrix. While the structure and organic composition of enamel are different from those of dentin and bone, the principal molecular mechanisms of protein-protein interactions, protein self-assembly, and control of crystallization events by the organic matrix are common among these apatite-containing tissues. This review briefly summarizes enamel and dentin matrix components and their interactions with other extracellular matrix components and calcium ions in mediating the mineralization process. We highlight the crystallization events that are controlled by the protein matrix and their interactions in the extracellular matrix during enamel and dentin biomineralization. Strategies for peptide-inspired biomimetic growth of tooth enamel and bioinspired mineralization of collagen to stimulate repair of demineralized dentin and bone tissue engineering are also addressed.
Topics: Amelogenin; Biomineralization; Collagen; Dental Enamel; Dentin
PubMed: 34151644
DOI: 10.1177/00220345211018405 -
Periodontology 2000 Feb 2019Periodontitis is a chronic inflammatory condition leading to destruction of the tooth supporting tissues, which if left untreated may cause tooth loss. The treatment of... (Review)
Review
Periodontitis is a chronic inflammatory condition leading to destruction of the tooth supporting tissues, which if left untreated may cause tooth loss. The treatment of periodontitis mainly aims to arrest the inflammatory process by infection control measures, although in some specific lesions a limited periodontal regeneration can also be attained. Current regenerative approaches are aimed to guide the cells with regenerative capacity to repopulate the lesion and promote new cementum and new connective tissue attachment. The first phase in periodontal tissue regeneration involves the differentiation of mesenchymal cells into cementoblasts to promote new cementum, thus facilitating the attachment of new periodontal ligament fibers to the root and the alveolar bone. Current regenerative approaches limit themselves to the confines of the lesion by promoting the self-regenerative potential of periodontal tissues. With the advent of bioengineered therapies, several studies have investigated the potential use of cell therapies, mainly the use of undifferentiated mesenchymal cells combined with different scaffolds. The understanding of the origin and differentiation patterns of these cells is, therefore, important to elucidate their potential therapeutic use and their comparative efficacy with current technologies. This paper aims to review the in vitro and experimental studies using cell therapies based on application of cementoblasts and mesenchymal stem cells isolated from oral tissues when combined with different scaffolds.
Topics: Bone Regeneration; Connective Tissue; Dental Cementum; Guided Tissue Regeneration, Periodontal; Humans; Periodontal Ligament; Periodontitis; Periodontium; Regeneration
PubMed: 30892768
DOI: 10.1111/prd.12250 -
International Journal of Oral Science Jan 2019Tooth enamel is a complex mineralized tissue consisting of long and parallel apatite crystals configured into decussating enamel rods. In recent years, multiple... (Review)
Review
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.
Topics: Acid Etching, Dental; Amelogenin; Biomimetics; Dental Enamel; Dental Enamel Proteins; Dentistry; Tissue Engineering; Tooth Remineralization
PubMed: 30610185
DOI: 10.1038/s41368-018-0038-6 -
International Journal of Molecular... Jun 2020Tooth enamel is the outer covering of tooth crowns, the hardest material in the mammalian body, yet fracture resistant. The extremely high content of 95 wt% calcium... (Review)
Review
Tooth enamel is the outer covering of tooth crowns, the hardest material in the mammalian body, yet fracture resistant. The extremely high content of 95 wt% calcium phosphate in healthy adult teeth is achieved through mineralization of a proteinaceous matrix that changes in abundance and composition. Enamel-specific proteins and proteases are known to be critical for proper enamel formation. Recent proteomics analyses revealed many other proteins with their roles in enamel formation yet to be unraveled. Although the exact protein composition of healthy tooth enamel is still unknown, it is apparent that compromised enamel deviates in amount and composition of its organic material. Why these differences affect both the mineralization process before tooth eruption and the properties of erupted teeth will become apparent as proteomics protocols are adjusted to the variability between species, tooth size, sample size and ephemeral organic content of forming teeth. This review summarizes the current knowledge and published proteomics data of healthy and diseased tooth enamel, including advancements in forensic applications and disease models in animals. A summary and discussion of the status quo highlights how recent proteomics findings advance our understating of the complexity and temporal changes of extracellular matrix composition during tooth enamel formation.
Topics: Animals; Dental Enamel; Dental Enamel Proteins; Extracellular Matrix; Humans; Proteome; Tooth
PubMed: 32585904
DOI: 10.3390/ijms21124458 -
F1000Research 2020Human enamel once formed cannot be biologically repaired or replaced. Saliva has a significant role in remineralization of dental enamel. It not only has a buffering... (Review)
Review
Human enamel once formed cannot be biologically repaired or replaced. Saliva has a significant role in remineralization of dental enamel. It not only has a buffering capacity to neutralize the oral cavity's low pH generated after acidic encounters, but also acts as a carrier of essential ions, such as fluoride, calcium and phosphate, which have a positive role in enamel's remineralization. This review discusses how salivary contents, like proteins and enzymes, have a natural role in enamel's mineralization. In addition, the presence of ions, such as fluoride, calcium and phosphate, in saliva further enhances its capability to remineralize the demineralized enamel surface. The review further examines modern innovative technologies, based on biomimetic regeneration systems, including dentin phosphoproteins, aspartate-serine-serine, recombinant porcine amelogenin, leucine-rich amelogenin peptide and nano-hydroxyapatite, that promote enamel remineralization. Fluoride boosters like calcium phosphates, polyphosphates, and certain natural products can also play an important role in enamel remineralization.
Topics: Animals; Calcium; Dental Enamel; Fluorides; Humans; Phosphates; Swine; Tooth Remineralization
PubMed: 32201577
DOI: 10.12688/f1000research.22499.3 -
Matrix Biology : Journal of the... Aug 2024Extracellular matrix proteins play crucial roles in the formation of mineralized tissues like bone and teeth via multifunctional mechanisms. In tooth enamel,... (Review)
Review
Extracellular matrix proteins play crucial roles in the formation of mineralized tissues like bone and teeth via multifunctional mechanisms. In tooth enamel, ameloblastin (Ambn) is one such multifunctional extracellular matrix protein implicated in cell signaling and polarity, cell adhesion to the developing enamel matrix, and stabilization of prismatic enamel morphology. To provide a perspective for Ambn structure and function, we begin this review by describing dental enamel and enamel formation (amelogenesis) followed by a description of enamel extracellular matrix. We then summarize the established domains and motifs in Ambn protein, human amelogenesis imperfecta cases, and genetically engineered mouse models involving mutated or null Ambn. We subsequently delineate in silico, in vitro, and in vivo evidence for the amphipathic helix in Ambn as a proposed cell-matrix adhesive and then more recent in vitro evidence for the multitargeting domain as the basis for dynamic interactions of Ambn with itself, amelogenin, and membranes. The multitargeting domain facilitates tuning between Ambn-membrane interactions and self/co-assembly and supports a likely overall role for Ambn as a matricellular protein. We anticipate that this review will enhance the understanding of multifunctional matrix proteins by consolidating diverse mechanisms through which Ambn contributes to enamel extracellular matrix mineralization.
Topics: Humans; Animals; Dental Enamel Proteins; Amelogenesis; Amelogenesis Imperfecta; Mice; Dental Enamel; Extracellular Matrix; Amelogenin; Cell Adhesion
PubMed: 38815936
DOI: 10.1016/j.matbio.2024.05.007 -
Frontiers in Physiology 2022Phosphorylation of serine residues has been recognized as a pivotal event in the evolution of mineralized tissues in many biological systems. During enamel development,...
Phosphorylation of serine residues has been recognized as a pivotal event in the evolution of mineralized tissues in many biological systems. During enamel development, the extracellular matrix protein amelogenin is most abundant and appears to be critical to the extreme high aspect ratios (length:width) of apatite mineral fibers reaching several millimeters in larger mammalian teeth. A 14-residue peptide (14P2, residues Gly8 to Thr21) was previously identified as a key sequence mediating amelogenin assembly formation, the domain also contains the native single phosphoserine residue (Ser16) of the full-length amelogenin. In this research, 14P2 and its phosphorylated form (p14P2) were investigated at pH 6.0 with various calcium and phosphate ion concentrations, indicating that both peptides could self-assemble into amyloid-like conformation but with differences in structural details. With calcium, the distance between P within the p14P2 self-assemblies is averaged to be 4.4 ± 0.2Å, determined by solid-state NMR P PITHIRDS-CT experiments. Combining with other experimental results, solid-state Nuclear Magnetic Resonance (SSNMR) suggests that the p14P2 self-assemblies are in parallel in-register -sheet conformation and divalent calcium ions most likely connect two adjacent peptide chains by binding to the phosphate group of Ser16 and the carboxylate of Glu18 side-chain. This study on the interactions between calcium ions and amelogenin-derived peptides provides insights on how amelogenin may self-assemble in the presence of calcium ions in early enamel development.
PubMed: 36589425
DOI: 10.3389/fphys.2022.1063970 -
Journal of Materials Chemistry. B 2015Mature tooth enamel is acellular and does not regenerate itself. Developing technologies that rebuild tooth enamel and preserve tooth structure is therefore of great...
Mature tooth enamel is acellular and does not regenerate itself. Developing technologies that rebuild tooth enamel and preserve tooth structure is therefore of great interest. Considering the importance of amelogenin protein in dental enamel formation, its ability to control apatite mineralization , and its potential to be applied in fabrication of future bio-inspired dental material this review focuses on two major subjects: amelogenin and enamel biomimetics. We review the most recent findings on amelogenin secondary and tertiary structural properties with a focus on its interactions with different targets including other enamel proteins, apatite mineral, and phospholipids. Following a brief overview of enamel hierarchical structure and its mechanical properties we will present the state-of-the-art strategies in the biomimetic reconstruction of human enamel.
PubMed: 26251723
DOI: 10.1039/C5TB00163C -
Frontiers in Physiology 2022Enamel research experienced an unprecedented period of growth during the latter part of the 20th century until today. This growth is in part due to the contributions of... (Review)
Review
Enamel research experienced an unprecedented period of growth during the latter part of the 20th century until today. This growth is in part due to the contributions of a number of iconic scientists such as Alan G. Fincham, the focus of the present review. Alan was involved in many of the seminal discoveries of this time, including the identification of the critical amelogenin peptides TRAP and LRAP, the determination of the amelogenin amino acid sequence, the identification of the sole serin-16 phosphorylation site, and the amelogenin nanosphere theory. Alan was also a superb mentor to graduate students and others. His experience and leadership related to problem-based learning greatly affected predoctoral dental education at the University of Southern California and in the United States.
PubMed: 36545279
DOI: 10.3389/fphys.2022.1071265 -
Journal of Structural Biology Dec 2021During enamel formation, the organic enamel protein matrix interacts with calcium phosphate minerals to form elongated, parallel, and bundled enamel apatite crystals of... (Review)
Review
During enamel formation, the organic enamel protein matrix interacts with calcium phosphate minerals to form elongated, parallel, and bundled enamel apatite crystals of extraordinary hardness and biomechanical resilience. The enamel protein matrix consists of unique enamel proteins such as amelogenin, ameloblastin, and enamelin, which are secreted by highly specialized cells called ameloblasts. The ameloblasts also facilitate calcium and phosphate ion transport toward the enamel layer. Within ameloblasts, enamel proteins are transported as a polygonal matrix with 5 nm subunits in secretory vesicles. Upon expulsion from the ameloblasts, the enamel protein matrix is re-organized into 20 nm subunit compartments. Enamel matrix subunit compartment assembly and expansion coincide with C-terminal cleavage by the MMP20 enamel protease and N-terminal amelogenin self-assembly. Upon enamel crystal precipitation, the enamel protein phase is reconfigured to surround the elongating enamel crystals and facilitate their elongation in C-axis direction. At this stage of development, and upon further amelogenin cleavage, central and polyproline-rich fragments of the amelogenin molecule associate with the growing mineral crystals through a process termed "shedding", while hexagonal apatite crystals fuse in longitudinal direction. Enamel protein sheath-coated enamel "dahlite" crystals continue to elongate until a dense bundle of parallel apatite crystals is formed, while the enamel matrix is continuously degraded by proteolytic enzymes. Together, these insights portrait enamel mineral nucleation and growth as a complex and dynamic set of interactions between enamel proteins and mineral ions that facilitate regularly seeded apatite growth and parallel enamel crystal elongation.
Topics: Ameloblasts; Amelogenesis; Amelogenin; Animals; Apatites; Calcium; Calcium Phosphates; Crystallization; Dental Enamel; Dental Enamel Proteins; Humans; Microscopy, Electron; Minerals
PubMed: 34748943
DOI: 10.1016/j.jsb.2021.107809