Objective: This in situ study compared the effectiveness of two toothpastes containing hydroxyapatite or 500 ppm fluoride in promoting remineralization and inhibiting caries development. Materials and methods: Two enamel blocks (human primary teeth), one sound and one with artificially-produced caries lesion, were exposed to toothpaste containing either 10% hydroxyapatite or 500 ppm F⁻ (amine fluoride) via intra-oral appliance worn by 30 adults in two-arm double blind randomized crossover study lasting 14 days per arm (ClinicalTrials.gov: NCT03681340). Baseline and post-test mineral loss and lesion depth (LD) were quantified using microradiography. One-sided t-test of one group mean was used for intragroup comparison (baseline vs. post-test), while two-sided t-test of two independent means was used to compare the two toothpaste groups. Results: Pairwise comparison (baseline vs. test) indicated significant (p < 0.0001) remineralization and LD reduction by either toothpaste; however, when compared against each other, there was no statistically significant difference in remineralization or LD reduction between the two toothpastes. No demineralization could be observed in sound enamel blocks exposed to either toothpaste. While F⁻ induced lesion surface lamination, HAP produced a more homogenous lesion remineralization. Conclusions: 10% hydroxyapatite achieved comparable efficacy with 500 ppm F⁻ in remineralizing initial caries and preventing demineralization. Thus the HAP toothpaste is confirmed to be equal to the fluoride toothpaste in this study.

Objective: The present in vitro study investigated if simulated daily use of hydroxyapatite-based gel (15% HAP) remineralizes early caries lesions as effective as weekly use of high fluoride (12,500 ppm) concentration gel, comparing them with artificial saliva alone. Materials and methods: Three tooth blocks were produced from each of 20 bovine teeth. Caries-like lesion was created on each block by 4-day demineralization in acidified gel. The blocks were randomized into three remineralization groups (20 blocks/group); Hydroxyapatite-based gel (Karex gelée, 15% HAP, fluoride-free), fluoride-based gel (Elmex gelée, 12,500 ppm F⁻), and artificial saliva (AS). Remineralization was conducted using pH-cycling model for 28 days with storage in AS. The pH cycling model consisted of 2 h demineralization once daily for all groups, and 3 min HAP gel application once daily, 3 min fluoride gel application once weekly, or remain in AS only respectively. Baseline and post-test mineral loss were quantified using microradiography. Results: Paired t-tests (baseline vs. post-Test) indicated significant (p < 0.0001) remineralization in all groups. When compared against each other using Games-Howell’s multiple comparison test, no significant difference in remineralization was observed between the two gels, but both gels exhibited significantly (p < 0.001) higher percentage mineral gain (HAP:39 ± 7%; fluoride:41 ± 11%) than AS alone (6 ± 2%). Conclusion: Hydroxyapatite-based gel (15% HAP) was as effective as fluoride-based gel (12,500 ppm F⁻) in remineralizing initial caries lesion.

Salivary gland (SG) dysfunction, due to radiotherapy, disease, or aging, is a clinical manifestation that has the potential to cause severe oral and/or systemic diseases and compromise quality of life. Currently, the standard-of-care for this condition remains palliative. A variety of approaches have been employed to restore saliva production, but they have largely failed due to damage to both secretory cells and the extracellular matrix (niche). Transplantation of allogeneic cells from healthy donors has been suggested as a potential solution, but no definitive population of SG stem cells, capable of regenerating the gland, has been identified. Alternatively, mesenchymal stem cells (MSCs) are abundant, well characterized, and during SG development/homeostasis engage in signaling crosstalk with the SG epithelium. Further, the trans-differentiation potential of these cells and their ability to regenerate SG tissues have been demonstrated. However, recent findings suggest that the “immuno-privileged” status of allogeneic adult MSCs may not reflect their status post-transplantation. In contrast, autologous MSCs can be recovered from healthy tissues and do not present a challenge to the recipient’s immune system. With recent advances in our ability to expand MSCs in vitro on tissue-specific matrices, autologous MSCs may offer a new therapeutic paradigm for restoration of SG function.

Salivary gland (SG) extracellular matrix (ECM) has a major influence on tissue development, homeostasis, and tissue regeneration after injury. During aging, disease, and physical insult, normal remodeling of the SG microenvironment (i.e. ECM) becomes dysregulated, leading to alterations in matrix composition which disrupt tissue architecture/structure, alter cell activity, and negatively impact gland function. Matrix metalloproteinases (MMPs) are a large and diverse family of metalloendopeptidases which play a major role in matrix degradation and are intimately involved in regulating development and cell function; dysregulation of these enzymes leads to the production of a fibrotic matrix. In the SG this altered fibrotic ECM (or cell microenvironment) negatively impacts normal cell function and the effectiveness of gene and stem cell therapies which serve as a foundation for many SG regenerative therapies. For this reason, prospective regenerative strategies should prioritize the maintenance and/or restoration of a healthy SG ECM. Mesenchymal stem cells (MSCs) have great potential for mitigating damage to the SG microenvironment by ameliorating inflammation, reducing fibrosis, and repairing the damaged milieu of extracellular regulatory cues, including the matrix. This review addresses our current understanding of the impact of aging and disease on the SG microenvironment and suggests critical deficiencies and opportunities in ECM-targeted therapeutic interventions.

This study validated a microbial caries model (artificial mouth) for dental caries development to determine the optimal time to create early caries suitable for evaluation of the efficacy of caries therapeutic agents. In all, 40 human enamel blocks were placed in an artificial mouth at 37 °C and 5% CO₂ and were exposed to brain heart infusion broth inoculated with S. mutans in continuous circulation (0.3 mL/min). The culture medium was replaced three times daily. Samples were exposed to 10% sucrose for 3 min, 3 times daily to promote biofilm growth. Five samples were harvested from the chamber after 3, 4, 5, 6, 7, 14, 21, and 28 days. At the end of experiment, samples were assessed visually by ICDAS criteria, while lesion depth (LD) and mineral loss (ML) were measured using polarizing light microscopy and transverse microradiography. Data were analyzed by Pearson correlation, ANOVA, and Tukey comparison test (p < 0.05). Results showed significant and strong positive correlation (p < 0.01) between all variables and biofilm growth time. LD and ML profiles of 7-day lesions seem to be the most suitable for remineralization studies. In conclusion, using the evaluated artificial mouth, early-stage caries suitable for products’ evaluation studies was produced within 7 days of exposure to microbial biofilm.