Simvastatin embedded into poly(lactic-co-glycolic acid) (PLGA)-based scaffolds can stimulate bone regeneration in preclinical models. However, the ideal pharmacological dose has not been evaluated. This systematic review reports on the simvastatin doses used in preclinical studies and evaluates the regeneration of critical-sized bone defects. References were selected in a two-phase process. Electronic databases (Embase, LILACS, LIVIVO, PubMed, SCOPUS, and Web of Science) and grey literature databases (Google Scholar, Open Grey, and ProQuest) were searched until September 2022. The risk of bias was considered to be low based on the SYRCLE tool. We identified four studies in rat, two in parietal and two in calvaria bone, one in mouse parietal bone, and one in rabbit femur bone. Simvastatin, ranging from 8 to 100 µg, significantly increased bone formation in five studies, as compared to the scaffold alone based on µ-computed tomography, histomorphometric, and radiography analysis. The median increase in bone formation caused by simvastatin was 2.1-fold compared to the PLGA-based scaffold alone. There was, however, no significant correlation between the relative bone gain and the doses of simvastatin (p = 0.37). The data suggest that relatively lower doses of simvastatin can consistently promote preclinical bone regeneration. However, the interpretation of these data must consider the heterogenicity of the PLGA-scaffolds, the defect anatomy, the observation period, and the evaluation method.

This study investigated the potential of Cranberry extract to stimulate osteogenesis in vitro. The total phenolic and monomeric anthocyanin contents in the Cranberry were determined. Liquid chromatography coupled with mass spectrometry was used to identify the Cranberry’s constituents. To assess the Cranberry’s cytotoxicity, a thiazolyl blue tetrazolium bromide assay was employed. Concerning the osteogenesis potential of Cranberry, alkaline phosphatase (ALP) activity, bone morphogenetic protein 2 (BMP-2) expression, and extracellular matrix mineralization were evaluated. The total phenolic content was 522.72 ± 9.80 mg GAE g-1 ES and 364.95 ± 12.49 mg GAE/g detected by the Fast Blue BB and Folin–Ciocalteu method, respectively. For monomeric anthocyanin, the content was 460 ± 30 mg ECG g-1 ES. Moreover, Cranberry concentrations ranged from 62.5 to 500 mg/mL and were found to be biocompatible with osteoblasts and mesenchymal stromal cells. Regarding osteogenesis, 20 mg/mL of Cranberry promoted 2-fold more ALP activity and almost 1.5-fold more BMP-2 than compared to the positive control group. Additionally, 200 mg/mL of Cranberry stimulated a 1.7-fold increase in extracellular matrix mineralization compared to the positive control group. In conclusion, Cranberry displayed potential in stimulating early and late markers of osteogenesis. Its ability to promote osteogenesis and its biocompatibility at higher concentrations hold promise for future application into biomaterials for 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.