Abstract: The chemical analysis of dental hard tissues can provide information on previous drug use due to the deposition of drugs into this tissue. For the interpretation of analytical results in, e.g., postmortem toxicology or regarding archeological samples, the influence of drug dosing, consumption frequency, duration of intake and type of drug on analyte concentrations in teeth has to be characterized. To approximate these correlations, in vitro models were applied to investigate the time dependency of drug deposition via and against pulp pressure (perfusion studies) and the concentration dependency of drug deposition via oral cavity (incubation study) as well as the influence of de- and remineralization (pH cycling) on the incorporation of drugs in bovine dentin pellets. Some of the drugs of abuse most relevant in forensic case work (amphetamines, opiates, cocaine and benzoylecgonine) were applied. Concentrations in dentin samples were analyzed by liquid chromatography-tandem mass spectrometry (LC-MS/MS) after pulverization and extraction via ultrasonication with methanol. The studies showed that drug deposition in dentin likely depends on the physicochemical properties of the drug molecules as well as on the duration of contact with drugs via the blood stream and on drug concentrations present in the oral cavity. Higher drug concentrations in teeth can result from a more frequent or longer drug use. In addition, intake of higher doses or oral/inhalative consumption can also be expected to lead to higher drug concentrations. These findings can be helpful for the interpretation of postmortem cases

Abstract: Dental pulp regeneration strategies frequently result in hard tissue formation and pulp obliteration. The aim of this study was to investigate whether dental pulp stem cells (DPSCs) can be directed toward soft tissue differentiation by extracellular elasticity. STRO-1-positive human dental pulp cells were magnetically enriched and cultured on substrates with elasticities of 1.5, 15, and 28 kPa. The morphology of DPSCs was assessed visually. Proteins relevant in mechanobiology ACTB, ITGB1, FAK, p-FAK, TALIN, VINCULIN, PAXILLIN, ERK 1/2, and p-ERK 1/2 were detected by immunofluorescence imaging. Transcription of the pulp marker genes BMP2, BMP4, MMP2, MMP3, MMP13, FN1, and IGF2 as well as the cytokines ANGPT1, VEGF, CCL2, TGFB1, IL2, ANG, and CSF1 was determined using qPCR. A low stiffness, i.e., 1.5 kPa, resulted in a soft tissue-like phenotype and gene expression, whereas DPSCs on 28 kPa substrates exhibited a differentiation signature resembling hard tissues with a low cytokine expression. Conversely, the highest cytokine expression was observed in cells cultured on intermediate elasticity, i.e., 15 kPa, substrates possibly allowing the cells to act as "trophic mediators". Our observations highlight the impact of biophysical cues for DPSC fate and enable the design of scaffold materials for clinical pulp regeneration that prevent hard tissue formation

Abstract: Background: The ageing of the population and the importance of aesthetics has put pressure on the delivery of dental care. Bacterial infection in intra-oral cavities can develop into a pathogenic biofilm, which then induces inflammatory processes. One of the necessary dental treatment steps is the disinfection of the infected area, whether it is in the root canal, or in the periodontal, periapical, or peri-implant regions. The objective of this review was to assess the actual situation and trends in the treatments for three of the most important areas of dental health: peri-implantitis, periodontitis, and endodontics. Methods: Results from clinical studies, reports from dental associations, national health insurance records, and market reports were used to quantify the number of treatment needs. For peri-implantitis, the number of inserted implants and the prevalence of peri-implantitis build the basis for the computation. For periodontitis and root canal treatments (RCTs), health insurance figures, and reports on dental instrument orders are the data sources for the estimations. Results: The data show that the number of performed periodontitis and RCTs increase linearly over the year, mainly driven by demographic changes, i.e., increase in size and age of populations. The computed values show that the treatment need for peri-implantitis follows an exponential growth and may surpass that of periodontitis by 2023 in Europe and in the USA. Conclusion: Where dental implantology is growing, the rapid development of peri-implant diseases will burden the health systems. This should be addressed at different levels. At the practitioners' level, this includes continuous training of staff and (re)investment in adequate material and infrastructures. At the governmental level, it includes policy development and reimbursement strategies as well as information dissemination in health insurance and dental associations. Last, but not least, R&D efforts in the public and private sectors should be implemented/boosted

Abstract: This study aimed to evaluate the in vivo initial microbial adhesion of oral microorganisms on the biomaterial Biodentine compared to MTA and AH Plus. Cylindrical samples of the materials were prepared, and dentin slabs served as a control. An individual intraoral lower jaw splint served as a carrier for the samples and was worn by six volunteers. The specimens were worn for 120 min. Adherent bacteria were quantified by determining the colony-forming units (CFUs), while the visualization and quantification of total adherent microorganisms were facilitated by using DAPI and live/dead staining combined with fluorescence microscopy. Bovine dentin had a significantly higher number of aerobic CFUs compared to Biodentine (p = 0.017) and MTA (p = 0.013). The lowest amounts of DAPI-stained adherent microorganisms were quantified for Biodentine (15% ± 9%) and the control (18% ± 9%), while MTA showed the highest counts of initially adherent microorganisms (38% ± 10%). Significant differences were found for MTA and Biodentine (p = 0.004) as well as for MTA and the control (p = 0.021) and for AH Plus and the control (p = 0.025). Biodentine inhibited microbial adherence, thereby yielding an antimicrobial effectivity similar to that of MTA

Abstract: Objective. To reduce secondary caries, glass ionomer luting cements are often used for cementing of indirect restorations. This is because of their well-known antimicrobial potential through the release of fluoride ions. The aim of this in vitro study was to investigate the antimicrobial effect of five dental luting cements which were based on glass ionomer cement technology. Methods. Five different glass ionomer based luting cements were tested for their antimicrobial effects on Streptococcus mutans in two different experimental setups: (i) determination of colony-forming units (CFUs) in a plate-counting assay; (ii) live/dead staining (LDS) and fluorescence microscopy. All experiments were conducted with or without prior treatment of the materials using sterilized human saliva. Antimicrobial effects were evaluated for adherent and planktonic bacteria. Bovine enamel slabs (BES) were used as negative control. BES covered with 0.2% chlorhexidine (CHX) served as positive control. Results. Each of the tested materials significantly reduced the number of initially adhered CFUs; this reduction was even more pronounced after prior incubation in saliva. Antimicrobial effects on adherent bacteria were confirmed by live-dead staining. Conclusion. All five luting cements showed an antimicrobial potential which was increased by prior incubation with human saliva, suggesting an enhanced effect in vivo

Abstract: The "leaky gut" syndrome describes a damaged (leaky) intestinal mucosa and is considered a serious contributor to numerous chronic diseases. Chronic inflammatory bowel diseases (IBD) are particularly associated with the "leaky gut" syndrome, but also allergies, autoimmune diseases or neurological disorders. We developed a complex in vitro inflammation-triggered triple-culture model using 21-day-differentiated human intestinal Caco-2 epithelial cells and HT29-MTX-E12 mucus-producing goblet cells (90:10 ratio) in close contact with differentiated human macrophage-like THP-1 cells or primary monocyte-derived macrophages from human peripheral blood. Upon an inflammatory stimulus, the characteristics of a "leaky gut" became evident: a significant loss of intestinal cell integrity in terms of decreased transepithelial/transendothelial electrical resistance (TEER), as well as a loss of tight junction proteins. The cell permeability for FITC-dextran 4 kDa was then increased, and key pro-inflammatory cytokines, including TNF-alpha and IL-6, were substantially released. Whereas in the M1 macrophage-like THP-1 co-culture model, we could not detect the release of IL-23, which plays a crucial regulatory role in IBD, this cytokine was clearly detected when using primary human M1 macrophages instead. In conclusion, we provide an advanced human in vitro model that could be useful for screening and evaluating therapeutic drugs for IBD treatment, including potential IL-23 inhibitors