Sinus augmentation using a histone deacetylase inhibitor in a calcium sulfate carrier in rabbit: A pilot study

Histone deacetylase inhibitors such as sodium butyrate (SB) have been suggested to be promising candidate small molecules for bone regeneration. In this study, the capacity of SB loaded onto calcium sulfate (CaS) to enhance bone formation was investigated in a rabbit sinus model. Following preparation of the sinus access window on a randomly selected side, SB loaded onto CaS (CaS/SB) was grafted in five rabbits, and CaS alone (control) was grafted in another five rabbits. The animals were euthanized after 4 weeks for radiographic, histometric, and immunohistochemical analyses. There was a statistically significant difference in the total augmented volume between the groups in the radiographic analysis (158.22 ± 39.31 mm³ and 107.09 ± 39.69 mm³, respectively, p = 0.040). The CaS/SB group showed a larger portion of mature lamellar bone and a higher level of mineralization of bone trabeculae, characterized by more intense labeling with osteocalcin compared with the control group in the immunohistochemical analysis. The number of osteocalcin-positive cells within the central area of the augmented sinus was significantly higher in the CaS/SB group than in the control group (179 ± 26.0 mm² and 123 ± 33.2 mm², respectively, p = 0.027). In conclusion, CaS/SB exhibited superior osteogenic potential, especially in the central portion of the augmented sinus as well as improvement of the volume maintenance for sinus augmentation.