Objective: Osteogenic differentiation is a complex process, and its analysis requires several biomarkers. Allied with this, there are no standardized bioassays to monitor the activity of simvastatin in osteogenesis in vitro. Therefore, identifying the most efficient and sensitive bioassays may enhance the quality of in vitro studies, bridging the gap with in vivo findings, saving time and resources, and benefiting the community. This systematic review aimed to determine the most efficient bioassay for simvastatin’s osteogenic activity in vitro, in terms of sensitivity. Materials and Methods: In vitro studies evaluating undifferentiated mesenchymal cells treated with simvastatin were considered eligible. References were selected in a two-phase process. Electronic databases and the grey literature were screened up to September 2023. The Office of Health Assessment and Translation (OHAT) tool was used to assess the risk of bias. Certainty in cumulative evidence was evaluated using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) criteria. Data were analyzed considering extracellular matrix mineralization, alkaline phosphatase, and the expression of potential target genes, such as bone morphogenetic protein-2 (BMP-2), collagen type I, Runt-related transcription factor 2, osterix, osteocalcin, and osteopontin. Results: Fourteen studies were included. A “probably low” or a “definitely low” risk of bias was assigned to the included studies. The simvastatin concentration ranged from 0.1 nM to 10 µM. Considering a minimum 4-fold increase, simvastatin caused robust mineralization of the extracellular matrix in four studies (4.0-, 4.4-, 5.0-, and 39.5-fold). Moreover, simvastatin substantially increased BMP-2 expression in mesenchymal cells in three studies (4-, 11-, and 19-fold). Conclusion: Therefore, mineralization of the extracellular matrix and BMP-2 expression in mesenchymal cells are the most efficient bioassays for determining the osteogenic activity of simvastatin in vitro (high certainty level). These findings provide a standardized approach that can enhance the reliability and comparability of in vitro studies, bridging the gap with in vivo research and optimizing resources in the field of bone regeneration.

Objectives: Despite the increasing scientific evidence regarding the application of Cranberries in dentistry, a comprehensive understanding of their potential benefits, active constituents, and mechanisms of action remains lacking. Consequently, this narrative review aims to meticulously analyze and consolidate the existing scientific literature on the utilization of Cranberries for the prevention and treatment of oral diseases. Materials and Methods: Electronic databases (PubMed, Scopus, and Web of Science) were searched up to October 2025. This review included in vitro, in vivo, and clinical research studies. A two-phase selection process was carried out. In phase 1, two reviewers independently screened titles and abstracts to identify potentially eligible studies. In phase 2, the same reviewers performed the full-text assessments of the eligible articles. Results: Among the 93 eligible articles, most assessed Cranberry use in Cariology (n = 28) and Periodontics (n = 26). Biofilm and microbial virulence factors (n = 46) were the most frequently studied topics. Cranberry extract (n = 32) and high-molecular-weight non-dialyzable material (NDM) (n = 23) were the most evaluated Cranberry fractions. Overall, Cranberry-derived compounds were identified as non-toxic and demonstrated promising antimicrobial activity against dental caries-related microorganisms in preclinical studies (n = 20). Regarding periodontal and peri-implant diseases, Cranberry demonstrated host immune modulator effects, counteracting the inflammatory and destructive mechanisms (n = 8). Additionally, Cranberries presented benefits in reducing the inflammation associated with periodontal disease and temporal mandibular joint lesions (n = 1). Regarding dental erosion, Cranberry inhibited dentin erosion (n = 4); however, no effect was observed on enamel lesions (n = 2). As an antioxidant agent, Cranberry showed effectiveness in preventing dental erosion (n = 18). Beyond that, Cranberry neutralized reactive oxygen species generated immediately after dental bleaching, enhancing bond strength (n = 2) and counteracting the oxygen ions formed on the tooth surface following bleaching procedures (n = 3). In osteoclastogenesis assays, A-type proanthocyanidins inhibited bone resorption (n = 1). In osteogenic analysis, preservation of hydroxycarbonate apatite deposition and an increase in early and late osteogenic markers were observed (n = 2). Conclusions: Cranberry bioactive compounds, both individually and synergistically, exhibit substantial potential for diverse applications within dentistry, particularly in the prevention and management of oral and maxillofacial diseases. This review provides insights into the plausible incorporation of Cranberries in contemporary dentistry, offering readers an informed perspective on their potential role.