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Objectives Combination therapies of growth factors and scaffolds for bone tissue engineering are becoming routine for clinical use. BMP9 has previously been characterized as one of the most osteogenic inducers among the BMP superfamily; however, up until recently, BMP9 has only been available through adenovirus transfection experiments (gene therapy). While recombinant human (rh) BMP2 is regarded as the gold standard for bone regeneration with recombinant growth factors, recently the successful development of rh BMP9 brings intriguing new possibilities for future clinical use. The purpose of this pioneering study was to investigate the effects of rh BMP9 in comparison with rh BMP2 on an in vitro cell behavior of bone-forming osteoblasts when combined with a bone grafting material. Material and methods Undifferentiated mouse ST2 stromal bone marrow cells were seeded onto bovine-derived natural bone mineral ( NBM) particles treated with (i) control, (ii) rh BMP2 (10 ng/ml), (iii) rh BMP2 (100 ng/ml), (iv) rh BMP9 (10 ng/ml) and (v) rh BMP9 (100 ng/ml). The effects of rh BMPs were compared for cell adhesion at 8 h, cell proliferation at 1, 3 and 5 days and osteoblast differentiation as assessed by real-time PCR at 3 and 14 days for genes encoding Runx2, collagen1alpha2 ( COL1a2), alkaline phosphatase ( ALP) and osteocalcin ( OCN). Furthermore, ALP staining and alizarin red staining were used to investigate localization of osteoblast differentiation marker and mineralization on NBM. Results Although neither rh BMP2 nor rh BMP9 influenced cell attachment to NBM particles, both were able to stimulate cell proliferation at 3 days. Furthermore, all concentrations of rh BMPs were able to significantly induce mRNA levels of Runx2, COL1a2 and OCN at 3 days. Interestingly, only rh BMP9 was able to significantly upregulate mRNA levels of ALP up to eightfold, and ALP staining up to 25-fold, when compared to rh BMP2. In addition, only rh BMP9 (100 ng/ml) significantly increased alizarin red staining when compared to control and rh BMP2 (10 ng/ml) samples. Conclusion These results demonstrate that both rh BMP2 and rh BMP9 have osteopromotive properties on osteoblast differentiation. It was found that rh BMP9 additionally stimulated the osteopromotive potential of osteoblasts when compared to rh BMP2 by demonstrating higher levels of ALP expression and alizarin red staining. Further animal studies comparing both recombinant proteins are necessary to further characterize the osteoinductive potential of BMP9. [ABSTRACT FROM AUTHOR]

Within the past years, BMP9 has been characterized as one of the most osteogenic bone-inducers among the BMP family, however up until recently, BMP9 has only been available through adenovirus transfection experiments (gene therapy) not approved for clinical use. The aim of this study was to investigate recombinant rhBMP9 versus rhBMP2 at 2 concentrations (10 and 100 ng/mL) in combination with 2 bone grafts: (1) a natural bone mineral (NBM) without collagen versus (2) a novel NBM integrated with atelo-collagen type I (NBM-Col). Scanning electron microscopy revealed that while NBM demonstrated a mineralized roughened surface morphology, NBM-Col particles contained many more visible collagen fibrils throughout the scaffold surface significantly increasing rhBMP adsorption from 8 h to 10 days (as quantified by ELISA). Thereafter, ST2 preosteoblasts were used to investigate cell attachment, proliferation, and differentiation. While little change was observed for cell attachment/proliferation, osteoblast differentiation demonstrated a significant increase in alkaline phosphatase (ALP) activity when scaffolds were loaded with rhBMP9 when compared to rhBMP2. Furthermore, a 2-3 fold increase in alizarin red staining, and in mRNA levels of osteoblast differentiation markers Runx2, Collagen1α2, ALP, and osteocalcin was observed when rhBMP9 was combined with NBM-Col when compared to NBM without collagen at equivalent doses and when compared to rhBMP2. The results from this study demonstrate that (1) the use of rhBMP9 significantly and markedly induced osteoblast differentiation when compared to rhBMP2 and (2) the incorporation of atelo-collagen type I into NBM bone grafts markedly improved these findings by serving as a scaffold capable of improving growth factor adsorption and osteoblast behavior. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 408-418, 2017. [ABSTRACT FROM AUTHOR]

The goals of the study were to investigate the effects on bone bioactivity of a titanium dioxide layer formed by hydrothermal oxidation of a titanium surface with hydrogen peroxide (H 2 O 2 ) and loading with fibroblast growth factor-2 (FGF-2) in vitro and in vivo. Ti-6Al-4V discs were hydrothermally oxidized with H 2 O 2 and then loaded with FGF-2. After cytotoxicity testing, Ti-6Al-4V mini-implants were subjected to the same treatment, and their osteogenic potential was evaluated histologically in a rat model. H 2 O 2 hydrothermal oxidation resulted in a dense porous network structure and hydrophilic changes, which improved retention of FGF-2. Morphologically, the cell density was higher, cell elongation was more pronounced, and the cell adhesion area was significantly higher in FGF-2-loaded cells than in those without FGF-2. In a cell proliferation assay using mouse osteoblast-like cells, absorbance tended to increase over time, especially in the FGF-2 group after 7 and 14 days, and in a bone differentiation assay based on ALP activity, there was a significant increase in the FGF-2 group after 14 days. In the rat model, H 2 O 2 hydrothermal oxidation and FGF-2 loading both resulted in more laminar bone tissue in the bone marrow around the mini-implant. These results suggest that titanium surface functionalization by H 2 O 2 hydrothermal oxidation and FGF-2 may promote initial cell adhesion, proliferation, and osteodifferentiation, and enhance bone bioactivity. These effects all contribute to early bonding of an implant with the surrounding bone., (© 2022 Wiley Periodicals LLC.)

Alveolar bone defects caused by tooth loss often lead to challenges in implant dentistry, with a need for development of optimal bone biomaterials to predictably rebuild these tissues. To address this problem, we fabricated a novel bone block using platelet-rich fibrin (PRF) and Deproteinized Bovine Bone Mineral (DBBM), and characterized their mechanical and biological properties. The bone block was prepared by mixing DBBM, Liquid-PRF, and Solid-PRF fragments in various combinations as follows: (1) BLOCK-1 made with Solid-PRF fragments + DBBM, (2) BLOCK-2 made with Liquid-PRF + DBBM, (3) BLOCK-3 made with Solid-PRF fragments + Liquid-PRF + DBBM. The time for solidification and the degradation properties were subsequently recorded. Scanning electron microscopy (SEM) and tensile tests were carried out to investigate the microstructure and mechanical properties of each block. The bioactivity of the three groups towards osteoblast differentiation was also evaluated by culturing cells with the conditioned medium from each of the three groups including cell proliferation assay, cell migration assay, alkaline phosphatase (ALP) staining, and alizarin red staining (ARS), as well as by real-time PCR for genes encoding runt-related transcription factor 2 ( RUNX2 ), ALP , collagen type I alpha1( COL1A1 ) and osteocalcin ( OCN ). BLOCK-3 made with Solid-PRF fragments + Liquid-PRF + DBBM had by far the fastest solidification period (over a 10-fold increase) as well as the most resistance to degradation. SEM and tensile tests also revealed that the mechanical properties of BLOCK-3 were superior in strength when compared to all other groups and further induced the highest osteoblast migration and osteogenic differentiation confirmed by ALP, ARS and real-time PCR. PRF bone blocks made through the combination of Solid-PRF fragments + Liquid-PRF + DBBM had the greatest mechanical and biological properties when compared to either used alone. Future clinical studies are warranted to further support the clinical application of PRF bone blocks in bone regeneration procedures., Competing Interests: The authors declare that they have no conflicts of interest in this work., (© 2021 The Authors. Publishing Services by Elsevier B.V. on behalf of KeAi Communications Co. Ltd.)

Salivary gland cancer (SGC) has a comparatively poor prognosis and is prone to frequent recurrence and metastases. Therefore, the development of more effective chemotherapy against SGC is desirable. The aim of the present study was to investigate the antitumour effects of valproic acid (VPA) against SGC in vitro and in vivo. Two human SGC cell lines (HSY and HSG cells) were used in the present study. The effects of VPA on the proliferation of SGC cells in vitro were assessed by MTT assay. Cancer cells treated with VPA were subjected to cell cycle analysis by flow cytometry. In addition, the expression levels of p21 and p27 were examined by real-time RT-PCR to identify the mechanisms of the antitumour effect of VPA on SGC. The effects of VPA on cancer growth in vivo were evaluated in a xenograft model. VPA inhibited the proliferation of SGC cells in a dose-dependent manner in vitro. Degenerated cancer cells were observed at high concentrations of VPA. In the cell cycle analysis, VPA induced cell-growth inhibition and G1 arrest of cell cycle progression in both cancer cell lines in a time- and dose-dependent manner. VPA markedly upregulated the mRNA expression levels of both p21 and p27 in both SGC cell lines in a time-dependent manner. In the xenograft model experiment, VPA treatment markedly inhibited the growth of salivary gland tumours when compared with the growth of the untreated controls. VPA may be a valuable drug in the development of better therapeutic regimens for SGC.