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

Abstract

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 mm and 107.09 ± 39.69 mm , 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 mm and 123 ± 33.2 mm , 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. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 105B: 1916-1923, 2017.

Bone augmentation using small molecules with biodegradable calcium sulfate particles in a vertical onlay graft model in the rabbit calvarium

“…The primary goal of this study was to determine the synergistic effects of SB and DMOG combined with CaS on vertical bone augmentation by using an onlay graft model in the rabbit calvarium. This study found that SB and DMOG appeared to exert minimal synergistic effects on new bone formation in vertical bone augmentation, which contrast with previous in vivo studies finding improved bone regeneration within contained defects (Cha et al, ; Liu, Wang, Wu, Ni, & Liang, ; Woo et al, ).…”

“…DMOG and SB were used at a concentration of 100 μmol/L in this study, which was based on previous studies (Cha et al, ; Jung et al, ; Woo et al, ). A previous in vitro study found that DMOG and SB enhanced the differentiation of MC4 cells and increased the expression of angiogenic and osteogenic factors (Woo et al, ).…”

“…CaS particles in the form of alpha hemihydrate were prepared using a modified version of a previously described method (Jung et al, ). Preliminarily measured CaS powder (Silky‐Rock® yellow model stone; Whip‐Mix, Louisville, KY) and three types of small‐molecule solution containing SB (Merck Millipore, Billerica, MA), DMOG (Cayman Chemical, Ann Arbor, MI), and DMOG/SB at a concentration of 100 μmol/L were mixed at a 0.23 water/powder ratio (Cha et al, ; Woo et al, ). All of the CaS was hydrated and dried in dihydrate form (commonly called gypsum) and then formed into particles using a mortar and pestle.…”

“…Previous studies found that loading SB and DMOG onto CaS significantly enhanced new bone formation both in vitro and in vivo, (Cha et al, ; Jung et al, ; Woo et al, ) indicating a synergistic effect of these two small molecules. Examinations of the combined effects of SB and DMOG on bone regeneration in endocranial defects of rat calvaria showed that they led to increases in both angiogenic and osteogenic responses that were significant in vitro and mild in vivo.…”

Parathyroid Hormone (1-34) Might Not Improve Early Bone Healing after Sinus Augmentation in Healthy Rabbits

“…The metabolic rate is three to four times faster in rabbits than in humans, and the effects on bone healing can be confirmed within weeks [ 25 ]. Several studies using this model have shown differences between control and experimental groups at healing periods of 2 and 4 weeks [ 26 – 28 ].…”