## 4 Discussion
BMP-2 is critical for osteoblast maturation and bone formation. Previous studies have shown that RSV upregulates BMP-2 expression in osteoblast cultures [10; 11; 12; 13; 14; 15]. Hence, local delivery of RSV could theoretically stimulate alveolar bone regeneration by relieving inhibition of BMP-2. However, in the present study, using post-extraction alveolar defects, collagen sponges soaked with 1.2% RSV solution failed to histomorphometrically enhance early bone healing. At the same time points, defects receiving no treatment or collagen sponge alone showed evidence of greater amounts of new bone and osteoblast activity. Thus, while RSV exhibits pro-osteogenic molecular actions, this did not yield measurable differences compared to controls for healing non-critical-sized alveolar wounds. The efficacy differences between past in vitro studies [7; 8; 9; 11; 12; 13] and the current in vivo findings could potentially be due to variability in the localized concentration of active RSV within bony defects. Further work is needed to optimize the dose, kinetics, and delivery system to harness the molecular osteogenic potential of statins like RSV for enhancing clinical bone regeneration. Although the study did not provide clear evidence, RSV-loaded collagen sponges were used for alveolar bone regeneration. However, the osteogenic and anti-inflammatory properties of statins are promising [19; 20]. Future research should focus on optimizing the delivery vehicles and concentrations of RSV for bone regeneration. More inert carrier matrices should be explored to minimize the effects of inflammation on the healing process. The authors suggest using larger animal models to evaluate increased absolute concentrations or volumes of RSV that match clinically sized bone defects. The addition of RSV to bone grafts or scaffolds with osteoconductive properties may provide synergistic actions, coupling the biological benefits of statins with biophysical cues to stimulate bone growth. In the future, localized RSV therapy or other statins could become valuable adjuncts to enhance clinical outcomes for a variety of bone regenerative procedures. These could be combined with current regenerative approaches such as guided bone regeneration, ridge augmentation, sinus lifts, and peri-implant defect treatment. While further development is needed, the potential benefits of locally administered RSV or other statins are promising. This study has several limitations that should be considered. Firstly, there are only a limited number of anatomical areas where bone defects can be reproduced, and the alveolar area for the insertion of biomaterials is quite small. Additionally, the alveolar defect that was used may not have been large enough to allow for adequate volumes of RSV to produce a biological effect. The short duration of observation (six weeks) also limits the interpretation of early bone healing phases. Longer follow-up is necessary to ascertain the effects on bone maturation and remodeling. Furthermore, the carrier vehicle itself may have provoked inflammation that impaired regeneration. More inert vehicles should be investigated to optimize delivery. Finally, while histological and histomorphometric analyses provide useful two-dimensional information, advanced 3D micro-CT imaging and immunohistochemistry (IHC) are necessary for comprehensively characterizing the quality, architecture, cellularity, and protein expression profiles of regenerated bone. Micro-CT enables detailed 3D architectural analysis of regenerated bone, while IHC reveals the presence and localization of critical proteins involved in bone formation. The omission of these methods limits the interpretation of rosuvastatin's efficacy. Further studies with larger samples, longer durations, optimized delivery vehicles, and robust analytical methods, including 3D micro-CT imaging and IHC, are imperative to elucidate the regenerative mechanisms and potential of statins like RSV.