Introduction: Bone implant integration is highly variable. Retinoic acid (AR) regulates osteogenesis, partly through bone morphogenetic protein 7 (BMP-7) signaling. However, its impact on later-stage bone remodeling remains unclear. This study investigated all-trans retinoic acid (AR)'s role in a rat calvarial defect model using 3D-printed polylactic acid (PLA) implants. Methods: This study investigated AR's effects using a standardized rat calvarial defect model with 3D-printed PLA implants. Four groups were compared: (1) surgery alone; (2) surgery + PLA; (3) surgery + AR; (4) surgery + PLA + AR. The differences between groups were determined employing a 2-way ANOVA for each variable. A statistically significant value of P < 0.05 was considered. Results: Radiographic analysis revealed significantly increased bone formation in AR-treated groups. While BMP-7 levels were unaffected, AR's modulation of the inflammatory response and its influence on bone marrow stromal cell differentiation into osteoblasts are implicated. Discussion: These findings highlight AR's potential in enhancing bone regeneration through stem cell modulation within a biocompatible scaffold, highlighting its promise for regenerative medicine strategies. The osteogenic effect observed with the PLA + AR combination may be attributed to multiple mechanisms. AR has been shown to influence mesenchymal stem cell differentiation by regulating key transcription factors such as Runx2 and Osterix, promoting osteoblast lineage commitment. In addition, AR can enhance angiogenesis and extracellular matrix remodeling, indirectly supporting bone formation. The 3D-printed PLA scaffold provides a structural framework that favors cell adhesion, proliferation, and osteoconductivity. Conclusion: Together, these factors likely contribute synergistically to the observed enhancement in bone regeneration. Although our current study did not delve into molecular pathway analyses, we acknowledge this as a limitation and propose further investigation into the signaling cascades involved.
Dealmy et al. (Tue,) studied this question.