The purpose of this review is to highlight recent nanotechnological developments for remineralization of incipient caries lesions as well as biomimetic strategies for enamel synthesis based on the application of nanotechnology. Analysis of in vitro data indicates that apatite nanoparticles might be effective in reversing lesion progression in the outer but not in the deeper part of early caries lesions. To control caries-induced demineralization, investigators have developed calcium and phosphate or fluoride ion-releasing nanofillers, enabling resin composites to release ions, if the pH decreases under in vitro conditions. Extensive in vitro investigations of apatite crystallization have been performed to mimic the hierarchical topology of natural enamel. Strategies for formation of highly organized biomineralized structures include oriented aggregation of nanocrystallites or the assembly of apatite nanoparticles mediated by organic scaffolds. Despite all these promising in vitro experiments, the effectiveness of such strategies for the control of demineralization processes as well as for caries therapy still needs validation by clinical studies.

Polyphenols are natural substances that have been shown to provide various health benefits. Antioxidant, anti-inflammatory, and anti-carcinogenic effects have been described. At the same time, they inhibit the actions of bacteria, viruses, and fungi. Thus, studies have also examined their effects within the oral cavity. This review provides an overview on the different polyphenols, and their structure and interactions with the tooth surface and the pellicle. In particular, the effects of various tea polyphenols on bioadhesion and erosion have been reviewed. The current research confirms that polyphenols can reduce the growth of cariogenic bacteria. Furthermore, they can decrease the adherence of bacteria to the tooth surface and improve the erosion-protective properties of the acquired enamel pellicle. Tea polyphenols, especially, have the potential to contribute to an oral health-related diet. However, in vitro studies have mainly been conducted. In situ studies and clinical studies need to be extended and supplemented in order to significantly contribute to additive prevention measures in caries prophylaxis.

Hydroxyapatite nanoparticles (nano-HAP) are receiving considerable attention for dental applications, and their adhesion to enamel is well established. However, there are no reports concerning the effects of HAP on other dental materials, and most of the studies in this field are based on in vitro designs, neglecting the salivary pellicle-apatite interactions. Thus, this in situ pilot study aims to evaluate the effects of three hydroxyapatite-based solutions and their interactions with different dental material surfaces under oral conditions. Hence, two volunteers carried intraoral splints with mounted samples from enamel and from three dental materials: titanium, ceramics, and polymethyl-methacrylate (PMMA). Three HAP watery solutions (5%) were prepared with different shapes and sizes of nano-HAP (HAP I, HAP II, HAP III). After 3 min of pellicle formation, 10 ml rinse was performed during 30 sec. Rinsing with water served as control. Samples were accessed immediately after rinsing, 30 min and 2 h after rinsing. Scanning electron microscopy (SEM) and transmission electron microscopy (TEM) were used to characterize the particles, and SEM evaluated the pellicle-HAP interactions. SEM and TEM results showed a high variation in the size range of the particles applied. A heterogeneous HAP layer was present after 2 h on enamel, titanium, ceramics, and PMMA surfaces under oral conditions. Bridge-like structures were visible between the nano-HAP and the pellicle formed on enamel, titanium, and PMMA surfaces. In conclusion, nano-HAP can adhere not only to enamel but also to artificial dental surfaces under oral conditions. The experiment showed that the acquired pellicle act as a bridge between the nano-HAP and the materials’ surface.

The break of the epithelial barrier of gingiva has been a subject of minor interest, albeit playing a key role in periodontal pathology, transitory bacteraemia, and subsequent systemic low-grade inflammation (LGI). The significance of mechanically induced bacterial translocation in gingiva (e.g., via mastication and teeth brushing) has been disregarded despite the accumulated knowledge of mechanical force effects on tight junctions (TJs) and subsequent pathology in other epithelial tissues. Transitory bacteraemia is observed as a rule in gingival inflammation, but is rarely observed in clinically healthy gingiva. This implies that TJs of inflamed gingiva deteriorate, e.g., via a surplus of lipopolysaccharide (LPS), bacterial proteases, toxins, Oncostatin M (OSM), and neutrophil proteases. The inflammation-deteriorated gingival TJs rupture when exposed to physiological mechanical forces. This rupture is characterised by bacteraemia during and briefly after mastication and teeth brushing, i.e., it appears to be a dynamic process of short duration, endowed with quick repair mechanisms. In this review, we consider the bacterial, immune, and mechanical factors responsible for the increased permeability and break of the epithelial barrier of inflamed gingiva and the subsequent translocation of both viable bacteria and bacterial LPS during physiological mechanical forces, such as mastication and teeth brushing.

Periodontitis is considered a promoter of many systemic diseases, but the signaling pathways of this interconnection remain elusive. Recently, it became evident that certain microbial challenges promote a heightened response of myeloid cell populations to subsequent infections either with the same or other pathogens. This phenomenon involves changes in the cell epigenetic and transcription, and is referred to as ‘‘trained immunity’’. It acts via modulation of hematopoietic stem and progenitor cells (HSPCs). A main modulation driver is the sustained, persistent low-level transmission of lipopolysaccharide from the periodontal pocket into the peripheral blood. Subsequently, the neutrophil phenotype changes and neutrophils become hyper-responsive and prone to boosted formation of neutrophil extracellular traps (NET). Cytotoxic neutrophil proteases and histones are responsible for ulcer formations on the pocket epithelium, which foster bacteremia and endoxemia. The latter promote systemic low-grade inflammation (SLGI), a precondition for many systemic diseases and some of them, e.g., atherosclerosis, diabetes etc., can be triggered by SLGI alone. Either reverting the polarized neutrophils back to the homeostatic state or attenuation of neutrophil hyper-responsiveness in periodontitis might be an approach to diminish or even to prevent systemic diseases.