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.

This study evaluated the clinical survival rates of 170 Morse taper implants through clinical and mechanical parameters in different therapeutic approaches such as single crowns, fixed partial prostheses, and fixed full-arch prostheses. Patients referred to the Center on Education and Research on Dental Implants from May 2017 to July 2018 with the indication for dental implant therapy, aged >18 years, without periodontal disease, recent evidence of inflammatory activity or other oral disorders, current pregnancy, uncontrolled diabetes mellitus or heavy smoking habit were included in this study. After 12 weeks of healing since the implants were placed in the mandible and after 16 weeks following implants placed in the maxilla, patients returned to the Center for prosthetic rehabilitation. After implant therapy, all patients underwent periodical, clinical, and prosthetic examinations every 6 months. Prosthetic restorations involved 109 fixed reconstructions in function. Few prosthetic complications were reported (6.55%). Twenty implants were rehabilitated with cemented prostheses; from those, 1 crown suffered a loss in retention/decementation. Of the 148 implants rehabilitated with screwed-retained prostheses, 6.76% suffered prosthetic screw loosening. The cumulative implant survival rate was 98.2%. When peri-implant tissue health was evaluated, the keratinized mucosa band appeared related to peri-implant tissue stability. Thus, Morse taper implants represented a successful procedure for implant rehabilitation, with a high cumulative implant survival rate, low prevalence of biological and prosthetic complications, and good stability of peri-implant tissues over the assessed period.

Exosomes have emerged as promising cell-free therapeutic agents for tissue regeneration. However, chronic inflammation, a hallmark of periodontal disease, may impair their osteogenic potential. This systematic review evaluated how inflammatory conditions influence the ability of exosomes to modulate osteogenesis in human periodontal ligament stem cells (hPDLSC) in vitro. Electronic databases and grey literature were searched up to February 2026, and study selection followed a two-phase screening process. Risk of bias was assessed using the Risk of Bias in Dental Preclinical Research Tool (RobDMAT), while certainty of evidence was evaluated using adapted GRADE criteria. Primary outcomes included alkaline phosphatase (ALP) activity and extracellular matrix mineralization. Due to substantial heterogeneity across studies, a meta-analysis was not performed, and findings were synthesized qualitatively using fold-change comparisons. Six studies were included. Exosome-based interventions consistently enhanced osteogenic outcomes under inflammatory conditions, although with variable magnitude. Extracellular matrix mineralization showed robust increases (> 4-fold) in two studies (10.67- and 4.38-fold), moderate enhancement in one study (3.06-fold), and weak increases (< 2-fold) in three studies (1.95-, 1.60-, and 1.41-fold). ALP activity demonstrated predominantly moderate (3.04-, 3.30-, and 3.83-fold) to robust enhancement (5.50- and 6.75-fold). Limited evidence also suggested a reduction in pro-inflammatory mediators, although this outcome remains insufficiently explored. Exosomes appear to partially overcome the inhibitory effects of inflammation on osteogenesis in hPDLSC, supporting their potential as modulators of regenerative responses in inflammatory microenvironments. Nevertheless, the limited number of studies and methodological heterogeneity restrict the strength of current evidence. Graphical abstract