Dental enamel is a calcified tissue that forms the outer protective covering of the anatomical crown of a tooth ¹ . Enamel once formed cannot be biologically repaired or replaced ² . The oral cavity continuously goes through cycles of demineralization and remineralization ³ . Loosing minerals from the tooth after an acidic encounter is called demineralization, whereas restoration of these minerals back into the tooth structure is called remineralization ⁴ . During demineralization, the enamel surface becomes rough and rugged upon acidic encounter. Thus throughout the life of a tooth, there are enamel demineralization/remineralization cycles that dictate the extent of mineral balance and tissue integrity or degradation ³ . Human saliva has a buffering role and acts as a carrier of essential ions that can bring a constructive change in the structure of enamel, promoting remineralization ⁵ .

This review is aimed at providing an overview of enamel structure and an in-depth insight on its mineralization mechanism carried out by salivary contents. The summary of search strategy involved in this study is shown in Figure 1.

Dental enamel is composed of 96% inorganic material, 3% water, and 1% organic matrix ⁶ . The inorganic component of dental enamel is hydroxyapatite (HAP) crystal and human enamel is a hard, acellular, and avascular tissue ¹ . Being acellular, it cannot be automatically replaced or repaired if damaged ² . However, its very highly mineralized nature makes it extremely resistant to destruction ⁷ . Enamel’s high mineral content also makes it susceptible to demineralization by acids formed by bacteria in the mouth, which leads to dental caries ³ .

Tooth enamel is an intricate structure and requires a keen sense of three-dimensional geometry to appreciate it. Early micro-anatomical descriptions are incomplete and reflected the restrictions of light microscopy. Only after the advent of modern techniques using transmission and scanning electron microscopy, the more complex structure of enamel was revealed. Enamel’s composition includes fiber-like mineralized crystals and a small proportion of water and proteins that clamp the mineralized fibers with each other ⁸ . This arrangement of mineralized and non-mineralized components of enamel, disperses the forces passing through teeth and in this manner shields them from fractures ⁴ . Enamel is composed of discrete basic units called Enamel Rods (formerly enamel prisms), each surrounded by a rod sheath with these packed together and embedded in an inter-rod (inter-prismatic) substance ⁹ . Ameloblasts elaborate and secrete the enamel protein matrix that is subsequently mineralized by the addition of calcium phosphate crystallites ¹⁰ . When fully differentiated, ameloblasts are tall columnar cells fully equipped for protein synthesis ¹¹ . The secretory end of the cell develops a projection (Tome’s process) through which the protein matrix and crystallites are laid down ¹² . The appearance of the inter-rod (inter-prismatic) substance and rod sheath at a light microscope level is due to the changes in crystallite orientation as they are laid down by ameloblasts ¹³ . The main body of the enamel rod is ~5µm in diameter but towards the enamel surface, the diameter is greater ¹⁴ . The number of ameloblasts that form the enamel are thought to remain constant for each tooth ¹⁵ . At the beginning and end of amelogenesis, Tome’s process is absent at the secretory end of ameloblasts and unstructured enamel (rod-less/prism-less) is produced ¹⁶ . This prism-less enamel varies in thickness but there is a general agreement that prism-less enamel is composed of HAP crystals that are arranged parallel to one another and perpendicular to the enamel’s surface ¹⁷ .

It is quite a well-established fact that fluoride helps in the prevention of dental caries ¹⁸ . Fluoride has remained under extensive investigations because of its effects on the structure and properties of tooth minerals ¹⁹ . Ionic substitution is a common phenomenon in the oral cavity and two major stake holders are enamel and saliva ²⁰ . The carbonate ion can replace hydroxyl or phosphate ions, magnesium can replace calcium, and fluoride can replace hydroxyl ions in the crystal lattice ³ . These ionic substitutions have a significant influence on the behavior of apatite including its solubility ²¹ . It is well-known that fluoride in the saliva (when it comes in contact with enamel) replaces the hydroxyl ion in the apatite crystal structure thus changing HAP into fluorapatite, which is more resistant to acidic attacks ²² . Therefore, understanding human body glands, particularly salivary glands, prior to going into details on the influence of salivary contents on remineralization of enamel becomes necessary.

A gland is an organ that synthesizes a secretion for release and two major types of glands found in the human body are exocrine and endocrine glands ²³ . Exocrine glands produce and release substances on the epithelial surface via a duct (for example, salivary and sweat glands) ²⁴ . Endocrine glands secrete hormones directly into the bloodstream (rather than a duct) (for example, pituitary, thyroid and adrenal glands) ²⁴ . A salivary gland is an organ that releases a secretion in the oral cavity, and it is further classified into major and minor types ²⁵ . Major salivary glands are situated at a distance from the oral mucosa but are connected to it through extra glandular ducts ²⁶ . Minor salivary glands reside in the mucosa or sub mucosa and can open directly inside the oral cavity ²⁷ . The three major paired salivary glands in humans are parotid, submandibular, and sublingual glands ²⁸ . Among the minor salivary glands, the important ones are von Ebner, Weber, buccal, labial, and palatal glands ²⁹ .

Human saliva is comprised of numerous contents and therefore has various functions. Saliva is a fluid that protects the mouth against harmful microorganisms and irritants ³⁰ . It not only lubricates the oral tissues but also helps in various other functions, such as speech, mastication and swallowing, as well as protection of the teeth and oral tissues ³¹ . The ability of saliva to remineralize tooth enamel is dependent on various factors, discussed below.

There have been many recent innovative advances in systems that act through saliva to promote enamel remineralization, but that do not depend on fluoride therapies ⁵³ . Philip divided these systems into two categories: (i) biomimetic regeneration technologies; and (ii) systems that boost fluoride effectiveness ⁵³ . In the first category, the most important is tooth regeneration via dentin phosphoprotein (DPP). It has been shown previously that DPP has the ability to remineralize the tooth surface when it is present in a solution containing calcium and phosphate, just like saliva ⁵⁴ . Many new systems have been derived based on DPP and among them the most active in promoting remineralization is aspartate-serine-serine (8DSS) ⁵⁵ . Application of 8DSS to the enamel surface does not only prevent leaching of ions from the enamel surface, but also promotes binding of calcium and phosphate ions from the saliva ⁵³ . Amelogenin is an important protein that regulates the growth and maturation of enamel crystals in newly formed enamel matrix ¹⁵ . This protein is absent in mature enamel, meaning it cannot regenerate ⁵⁶ . Modern systems, such as recombinant porcine amelogenin (rP172) and leucine-rich amelogenin peptide, stabilize calcium phosphate to enhance crystal formation and direct mineral growth respectively ^{57, 58} . Nanohydroxyapatite is another bioactive material that can promote enamel remineralization ⁵³ . As these particles are very small (nano-sized), they bind strongly to the enamel surface and fill up the gaps and holes in the enamel surface to repair it ^{53, 59} .

In the second category, which are also known as fluoride promoters, many modern systems are available ⁵³ . The most significant are calcium phosphate based systems and among them, the most important is CPP-ACP ⁶⁰ . CPP-ACP particles are readily soluble in saliva and thus localize in plaque and act as a reservoir of calcium and phosphate ions ⁶¹ . Upon an acidic encounter, they release these ions to promote remineralization and inhibit demineralization ⁶¹ . Another material to boost enamel remineralization is bioactive glass, which is based on calcium sodium phosphosilicate composition ⁶² . It dissolves in aqueous solution to release sodium, calcium, and phosphate ions in the saliva, to which they interact, leading to deposition of a layer of HAP on the enamel’s surface ⁶³ . Another major system in the second category is polyphosphate-based systems and among them the most essential is sodium trimetaphosphate (STMP) ⁶⁴ . STMP not only promotes remineralization, but also inhibits its demineralization ⁶⁴ . Some other natural products, such as thymoquinone, have shown good capability in promoting enamel remineralization in vitro ⁶⁵ , but data on its in vivo effectiveness is still anticipated ⁶⁵ .

Enamel remineralization is vital for a tooth as it lacks the capability to regenerate it. More research on remineralizing materials is required as it would significantly decrease incidence of dental caries.

Saliva contains many important substances and also acts as a transporter of many important ions, such as calcium, phosphate and fluoride, which are essential for the promotion of remineralization. Pathogenicity of dental erosion and caries is directly influenced by the buffering capacity and contents of saliva. Saliva helps to maintain a constant reservoir of ions that help to neutralize the pH and prevent demineralization. Modern innovative technologies, for example biomimetic regeneration technologies, including dentin phosphoproteins, aspartate-serine-serine, recombinant porcine amelogenin, leucine-rich amelogenin peptide and nano-hydroxyapatite, promote enamel remineralization. Fluoride boosters, like calcium phosphates, polyphosphates and natural products, also play an important role in enamel remineralization.

No data are associated with this article.