Search Results (7)

Background/Objectives: Mathematical modelling provides a quantitative way to describe the fate and action of drugs in the oral cavity, where transport processes are shaped by salivary flow, pellicle formation, biofilm structure and the wash-out effect of gingival crevicular fluid (GCF). Local pharmacokinetics in the mouth differ substantially from systemic models, and therefore a dedicated framework is required. The aim of this work was to present a structured, physiologically based concept that links in vitro release testing with local pharmacokinetics and pharmacodynamics. Methods: A narrative review with elements of systematic search was conducted in PubMed, Scopus and Web of Science (1980–2025) for publications describing drug release, local PBPK, and PK/PD modelling in the oral cavity. Mathematical formulations were grouped into release kinetics, mini-PBPK transport and local PK/PD relations. Classical models (Higuchi, Korsmeyer–Peppas, Peppas–Sahlin) were integrated with a mini-PBPK structure describing saliva–mucosa–biofilm–pocket interactions. Results: The combined model captures adsorption to pellicle, diffusion within biofilm and wash-out by GCF. It allows simulation of variable clinical conditions, such as inflammation-related changes in Q_GCF, and links local exposure to pharmacodynamic outcomes. Case studies with PerioChip^®, Arestin^®, and Atridox^® demonstrate how mechanistic models explain observed therapeutic duration and low-systemic exposure. Conclusions: The proposed mini-PBPK framework bridges empirical release data and physiological transport in the oral cavity. It supports rational formulation design, optimisation of local dosage, and personalised prediction of drug retention in gingival pockets. This modelling approach can become a practical tool for the development of dental biomaterials and subgingival therapies. Full article

Organs-on-a-chip (OoCs) are microfluidic devices constituted by PDMS or hydrogel in which different layers of cells are separated by a semipermeable membrane. This technology can set many parameters, like fluid shear stress, chemical concentration gradient, tissue–organ interface, and cell interaction. The use of these devices in medical research permits the investigation of cell patterning, tissue–material interface, and organ–organ interaction, mimicking the complex structures and microenvironment of human and animal bodies. This technology allows us to reconstitute in vitro complex conditions that recapitulate in vivo environments. One of the main advantages of these systems is that they represent a very realistic model that, in many cases, can replace animal experimentation, eliminating costs and related ethical issues. Organ-on-a-chip can also contain bacteria or cancer cells. This technology could be beneficial in dentistry for testing novel antibacterial substances and biomaterials, performing studies on inflammatory disease, or planning preclinical studies. A significant number of publications and reviews have been published on this topic. Still, to our knowledge, they mainly focus on the materials used for fabrication and the different patterns of the chip applied to the experimentations. This review presents the most recent applications of organ-on-a-chip models in dentistry, starting from the reconstituted dental tissues to their clinical applications and future perspectives. Full article

Inflammatory bowel disease is a set of chronic inflammatory diseases that mainly develop in the gastrointestinal mucosa, including ulcerative colitis and Crohn’s disease. Gastrointestinal membrane permeability is an important factor influencing the pharmacological effects of pharmaceuticals administered orally for treating inflammatory bowel disease and other diseases. Understanding the presence or absence of changes in pharmacokinetic properties under a disease state facilitates effective pharmacotherapy. In this paper, we reviewed the gastrointestinal membrane function in ulcerative colitis and Crohn’s disease from the perspective of in vitro membrane permeability and electrophysiological parameters. Information on in vivo permeability in humans is summarized. We also overviewed the inflammatory bowel disease research using gut-on-a-chip, in which some advances have recently been achieved. It is expected that these findings will be exploited for the development of therapeutic drugs for inflammatory bowel disease and the optimization of treatment options and regimens. Full article

Epithelial cell function is modulated by mechanical forces imparted by the extracellular environment. The transmission of forces onto the cytoskeleton by modalities such as mechanical stress and matrix stiffness is necessary to address by the development of new experimental models that permit finely tuned cell mechanical challenges. Herein, we developed an epithelial tissue culture model, named the 3D Oral Epi-mucosa platform, to investigate the role mechanical cues in the epithelial barrier. In this platform, low-level mechanical stress (0.1 kPa) is applied to oral keratinocytes, which lie on 3D fibrous collagen (Col) gels whose stiffness is modulated by different concentrations or the addition of other factors such as fibronectin (FN). Our results show that cells lying on intermediate Col (3 mg/mL; stiffness = 30 Pa) demonstrated lower epithelial leakiness compared with soft Col (1.5 mg/mL; stiffness = 10 Pa) and stiff Col (6 mg/mL; stiffness = 120 Pa) gels, indicating that stiffness modulates barrier function. In addition, the presence of FN reversed the barrier integrity by inhibiting the interepithelial interaction via E-cadherin and Zonula occludens-1. Overall, the 3D Oral Epi-mucosa platform, as a new in vitro system, will be utilized to identify new mechanisms and develop future targets involved in mucosal diseases. Full article

The choice of an appropriate implant suprastructure, which should be made according to the individual characteristics of each patient, is a leading factor in achieving good aesthetic results. The aim of this study was to assess the clinical behavior of implant suprastructures according to functional, biological, and aesthetic criteria. Methods: The study enrolled 23 patients with a total of 27 implants in different areas of the oral cavity. The following groups were studied for a period of 1 year: Group A, the control group (monolithic implant crowns made of zirconium dioxide on a titanium base); Group B (monolithic implant crowns made of lithium disilicate with individualized (custom) titanium alloy abutment); and Group C (implant crowns made of zirconium dioxide with individualized titanium alloy abutment). The functional criteria included suprastructure fracture, crown fracture or chipping, screw fracture or loosening, faceting or wearing of the occlusal surface of the crown, articulation relations, and suprastructure fracture. The biological indicators included the probing pocket depth (PPD) and Mombelli et al.’s plaque index and bleeding on probing. The bone loss level was measured radiographically. Digital measurements of the bone loss level were performed when definitive prosthetics were placed and 1 year after. The platform of the implant was taken as a reference point. Two parallel lines ran distally and medially to the implant and descended to the level of the first thread, which was in contact with the bone. The aesthetic evaluation was based on Jempt’s papilla index and considered differences in the color of the peri-implant mucosa. The suprastructures were examined at 2 weeks and 1 year after the initiation of prosthetic treatment. Results: Regarding the functional criteria, no deviations from the reference range were registered in any of the study groups for both measurements. Radiography showed no bone loss in any of the study groups. Group B showed the best behavior regarding biological complications, followed by Group C. There was no plaque accumulation in Group B, but statistically significant amounts were found in Groups A (p = 0.08) and C (p = 0.01). Group B had the lowest bleeding index, but the differences between the groups were found to be insignificant during the observations at the one-year mark. On the vestibular side of the papillae, p = 0.39, while on the oral side, p = 0.35. The PPD measurements showed that there were statistically significant differences between the three groups when they were compared after the second week and after one year (p = 0.00). Jempt’s papilla height index showed the highest values in Group B, which increased by two times throughout the study period. The increase was statistically significant in Groups B and C, while the growth in Group A remained statistically insignificant (p = 0.10). The aesthetic indicator “Gingiva color around the restoration” showed mild margo gingivalis graying in Groups B and C. Conclusions: Individualized implant abutments made of titanium alloy and monolithic restorations made of lithium disilicate or zirconium dioxide have stable biomechanical behavior and may be the optimal choice for the prosthetic treatment of partial edentulousness. Because this study took place within a limited period of time, clinical trials with a longer follow-up period need to be carried out. Full article

Oral mucosa and salivary gland are composed of complex and dynamic networks of extracellular matrix, multiple cell types, vasculature, and various biochemical agents. Two-dimensional (2D) cell culture is commonly used in testing new drugs and experimental therapies. However, 2D cell culture cannot fully replicate the architecture, physiological, and pathological microenvironment of living human oral mucosa and salivary glands. Recent microengineering techniques offer state of the science cell culture models that can recapitulate human organ structures and functions. This narrative review describes emerging in vitro models of oral and salivary gland tissue such as 3D cell culture models, spheroid and organoid models, tissue-on-a-chip, and functional decellularized scaffolds. Clinical applications of these models are also discussed in this review. Full article

There is a strong need to find new, good biomarkers of head and neck squamous cell carcinoma (HNSCC) because of the bad prognoses and high mortality rates. The aim of this study was to identify the potential biomarkers in HNSCC that have differences in their DNA methylome and potentially premalignant oral lesions, in comparison to healthy oral mucosa. In this study, 32 oral samples were tested: nine healthy oral mucosae, 13 HNSCC, and 10 oral lesions for DNA methylation by the Infinium MethylationEPIC BeadChip. Our findings showed that a panel of genes significantly hypermethylated in their promoters or specific sites in HNSCC samples in comparison to healthy oral samples, which are mainly oncogenes, receptor, and transcription factor genes, or genes included in cell cycle, transformation, apoptosis, and autophagy. A group of hypomethylated genes in HNSCC, in comparison to healthy oral mucosa, are mainly involved in the host immune response and transcriptional regulation. The results also showed significant differences in gene methylation between HNSCC and potentially premalignant oral lesions, as well as differently methylated genes that discriminate between oral lesions and healthy mucosa. The given methylation panels point to novel potential biomarkers for early diagnostics of HNSCC, as well as potentially premalignant oral lesions. Full article