Erik Schulze Zur Wiesche

The demineralization of tooth enamel is the primary consequence of dental caries, leading to cavities and finally tooth loss. Erosive tooth wear from acidic beverages and food is another factor that degrades enamel. In both cases, an acidic environment leads to etching and the final dissolution of tooth mineral, i.e., hydroxyapatite. Here, this process is discussed from a chemical perspective, taking into account the solubility of calcium phosphate and the presence of the pellicle (protein layer) and plaque (bacterial biofilms), which both affect the dissolution rate. While low pH is definitely decisive, calcium-binding ligands (e.g., acid anions, proteins) contribute to dissolution by removing calcium ions from the equilibrium. This is an important effect in the oral cavity where the concentration of biomolecules is high. The situation is complicated by the fact that the composition of saliva and the oral microbiome vary considerably between individuals. The state of current knowledge on the demineralization of enamel is summarized and discussed, also in the context of approaches to prevent dental caries and erosive tooth wear.

The natural remineralization of enamel is of major importance for oral health. In principle, early erosions (demineralization) induced by acidic beverages and foods as well as initial caries lesions can be covered and remineralized by the deposition of calcium phosphate, i.e., tooth mineral. This remineralization effect is characterized by the presence of calcium and phosphate ions in saliva that form hydroxyapatite on the enamel surface. Although it is apparently a simple crystallization, it turns out that remineralization under in vivo conditions is actually a very complex process. Calcium phosphate can form a number of solid phases of which hydroxyapatite is only one. Precipitation involves the formation of metastable phases like amorphous calcium phosphate that convert into biological apatite in a number of steps. Nanoscopic clusters of calcium phosphate that can attach on the enamel surface are also present in saliva. Thus, remineralization under strictly controlled in vitro conditions (e.g., pH, ion concentrations, no additives) is already complex, but it becomes even more complicated under the actual conditions in the oral cavity. Here, biomolecules are present in saliva, which interact with the forming calcium phosphate mineral. For instance, there are salivary proteins which have the function of inhibiting crystallization to avoid overshooting remineralization. Finally, the presence of bacteria and an extracellular matrix in plaque and the presence of proteins in the pellicle have strong influences on the precipitation on the enamel surface. The current knowledge on the remineralization of the enamel is reviewed from a chemical perspective with a special focus on the underlying crystallization phenomena and the effects of biological compounds that are present in saliva, pellicle, and plaque. Basically, the remineralization of enamel follows the same principles as calculus formation. Notably, both processes are far too complex to be understood on a microscopic basis under in vivo conditions, given the complicated process of mineral formation in the presence of a plethora of foreign ions and biomolecules.

Molar incisor hypomineralization (MIH) is a highly prevalent dental developmental disorder with a significant health burden for patients and high treatment needs, yet no comprehensive review article on all remineralization systems as a non-invasive treatment approach for MIH has been published. Typical characteristics of MIH-affected teeth are a lower mineral density and lower hardness compared to healthy teeth leading to sensitivity and loss of function. Thus, the use of formulations with calcium phosphates to remineralize MIH-affected teeth is reasonable. This review presents an up-to-date overview of remineralization studies focusing on active ingredients investigated for remineralization of MIH, i.e., casein phosphopeptide amorphous calcium phosphate (CPP-ACP), casein phosphopeptide amorphous calcium fluoride phosphate (CPP-ACFP), hydroxyapatite, calcium glycerophosphate, self-assembling peptide, and fluoride. Overall, 19 studies (in vitro, in situ, and in vivo) were found. Furthermore, an additional search for studies focusing on using toothpaste/dentifrices for MIH management resulted in six studies, where three studies were on remineralization and three on reduction of sensitivity. Overall, the studies analyzed in this review showed that MIH-affected teeth could be remineralized using calcium phosphate-based approaches. In conclusion, calcium phosphates like CPP-ACP, calcium glycerophosphate, and hydroxyapatite can be used to remineralize MIH-affected teeth. In addition to MIH-remineralization, CPP-ACP and hydroxyapatite also offer relief from MIH-associated tooth sensitivity.

Hydroxyapatite, Ca₅(PO₄)₃(OH), is a biomimetic active ingredient, which is used in commercial oral care products such as toothpastes and mouthwashes worldwide. Clinical studies (in vivo) as well as in situ and in vitro studies have shown the preventive effects of hydroxyapatite in various field of oral care. In some products, hydroxyapatite is combined with other active ingredients, to achieve an additional antibacterial effect or to promote gum health. This review analyzes the efficacy of six selected natural and nature-inspired ingredients that are commonly used together with hydroxyapatite. These additional actives are either antibacterial (lactoferrin, xylitol, and zinc) or promote gum health (allantoin, bisabolol, and hyaluronic acid). A systematic literature search was performed, and all studies found on each ingredient were analyzed. In summary, all analyzed ingredients mentioned in this review are well described in scientific studies on their beneficial effect for oral health and can be used to expand the preventive effect of hydroxyapatite in oral care products.

The human body needs calcium and phosphate as essential nutrients to grow bones and teeth, but they are also necessary for many other biochemical purposes (e.g., the biosynthesis of phospholipids, adenosine triphosphate, ATP, or DNA). The use of solid calcium phosphate in particle form as a food additive is reviewed and discussed in terms of bioavailability and its safety after ingestion. The fact that all calcium phosphates, such as hydroxyapatite and tricalcium phosphate, are soluble in the acidic environment of the stomach, regardless of the particle size or phase, means that they are present as dissolved ions after passing through the stomach. These dissolved ions cannot be distinguished from a mixture of calcium and phosphate ions that were ingested separately, e.g., from cheese or milk together with soft drinks or meat. Milk, including human breast milk, is a natural source of calcium and phosphate in which calcium phosphate is present as nanoscopic clusters (nanoparticles) inside casein (protein) micelles. It is concluded that calcium phosphates are generally safe as food additives, also in baby formula.