• Journal of Periodontal and Implant Science
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• v.38 no.sup2
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• pp.325-334
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• 2008

Purpose: The carrier used as delivery agent for bone morphogenetic proteins(BMPs) should also act as a scaffold for new bone formation. Moreover, bone formation should be predictable in terms of the volume and shape. This study examined the osteogenic effect of macroporous biphasic calcium phosphate (MBCP) block combined with ePTFE membrane as a carrier for recombinant human bone morphogenetic proteins (rhBMP-2). In addition, the additive effect of ePTFE membrane on bone formation was evaluated. Materials and Methods: Eight-millimeter critical sized calvarial defects were created surgically in 28 male Sprague-Dawley rats. The animals were divided into 2 groups containing 14 animals each. The defects were treated with either rhBMP-2/MBCP block (rhBMP-2/MBCP group) or rhBMP-2/MBCP block/ePTFE membrane (rhBMP-2/MBCP/ePTFE group). A disc-shaped MBCP block (3 mm height and 8 mm diameter) was used as the carrier for the rhBMP-2 and ePTFE membrane was used to cover the rhBMP-2/MBCP block. The histologic and histometric parameters were used to evaluate the defects after 2- or 8-week healing period (7 animals/group/healing interval). Results: The level of bone formation in the defects of both groups was significantly higher at 8 weeks than that at 2 weeks (P < 0.05). The ePTFE membrane has no additional effect compared with the rhBMP-2/MBCP block only. However, at 8 weeks, rhBMP-2/MBCP/ePTFE group showed more even bone formation on the top of the MBCP block than the rhBMP-2/MBCP group. Conclusion: These results suggest that the ePTFE membrane has no additive effect on bone formation when a MBCP block is used as a carrier for rhBMP-2.

• Journal of Life Science
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• v.22 no.4
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• pp.456-465
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• 2012

Heterodimeric recombinant human bone morphogenetic proteins (rhBMPs) are powerful tools for bone tissue engineering. However, BMPs have several important limitations in their application to bone regeneration. BMPs have a short half-life and must be used in high concentrations, which may be cost-inefficient. To overcome these problems, we established a stable cell line that expressed the fusion protein comprised of recombinant human BMP2/7 heterodimer protein and PTD (rhBMP2/7-PTD). This stable cell line enabled high process yields by continuously expressing rhBMP2/7-PTD products at high levels throughout cultivation. This synthesized BMP7 was fused to a BMP2 protein with four glycine residues (to allow free bond rotation of the domains) and PTD. To demonstrate that the rhBMP2/7-PTD protein that was secreted from an rhBMP2/7-PTD-expressing stable cell line exhibited biological activity consistent with its role as an osteogenic differentiation induction growth factor, we evaluated BMP-induced ALP activity. Our results suggest that this cell line may be a powerful and efficient tool for applications such as bone tissue regeneration.

• Journal of Korean Neurosurgical Society
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• v.67 no.3
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• pp.354-363
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• 2024

Objective : This study aims to determine the optimal dose of recombinant-human bone morphogenic protein-2 (rhBMP-2) for successful bone fusion in minimally invasive lateral lumbar interbody fusion (MIS LLIF). Previous studies show that rhBMP is an effective alternative to autologous iliac crest bone graft, but the optimal dose remains uncertain. The study analyzes the fusion rates associated with different rhBMP doses to provide a recommendation for the optimal dose in MIS LLIF. Methods : Ninety-three patients underwent MIS LLIF using demineralized bone matrix (DBM) or a mixture of rhBMP-2 and DBM as fusion material. The group was divided into the following three groups according to the rhBMP-2 usage : group A, only DBM was used (n=27); group B, 1 mg of rhBMP-2 per 5 mL of DBM paste (n=41); and group C, 2 mg of rhBMP-2 per 5 mL of DBM paste (n=25). Demographic data, clinical outcomes, postoperative complication and fusion were assessed. Results : At 12 months post-surgery, the overall fusion rate was 92.3% according to Bridwell fusion grading system. Groups B and C, who received rhBMP-2, had significantly higher fusion rates than group A, who received only DBM. However, there was no significant increase in fusion rate when the rhBMP-2 dosage was increased from group B to group C. The groups B and C showed significant improvement in back pain and Oswestry disability index compared to the group A. The incidence of screw loosening was decreased in groups B and C, but there was no significant difference in the occurrence of other complications. Conclusion : Usage of rhBMP-2 in LLIF surgery leads to early and increased final fusion rates, which can result in faster pain relief and return to daily activities for patients. The benefits of using rhBMP-2 were not significantly different between the groups that received 1 mg/5 mL and 2 mg/5 mL of rhBMP-2. Therefore, it is recommended to use 1 mg of rhBMP-2 with 5 mL of DBM, taking both economic and clinical aspects into consideration.

• Journal of Periodontal and Implant Science
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• v.29 no.3
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• pp.447-472
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• 1999

The preclinical and clinical studies reviewed herein show that rhBMP-2 induces normal physiologic bone in relevant defects in the craniofacial skeleton. The newly formed bone assumes characteristics of the adjacent resident bone, and allows placement and osseointegration of dental implants. Clearly, the bone inducing capacity of rhBMP-2 is carrier and site dependent. rhBMP-2 in an absorbable collagen sponge carrier induces relevant bone formation in space providing defects. Space providing carries extends this possibility to non-space providing sites. Notably, some ceramic and polymeric biomaterials may substantially interfere with rhBMP-2 induced osteogenesis.

• The Journal of Advanced Prosthodontics
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• v.3 no.3
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• pp.145-151
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• 2011

PURPOSE. This study was performed to investigate the ability of recombinant human-bone morphogenic protein-2 immobilized on a heparin-grafted bone substrate to enhance the osteoblastic functions. MATERIALS AND METHODS. The Bio-$Oss^{(R)}$, not coated with any material, was used as a control group. In rhBMP-2-Bio-$Oss^{(R)}$ group, rhBMP-2 was coated with Bio-$Oss^{(R)}$ using only deep and dry methods (50 ng/mL, 24 h). In heparinized rhBMP-2-Bio-$Oss^{(R)}$ group, dopamine was anchored to the surface of Bio-$Oss^{(R)}$, and coated with heparin. rhBMP-2 was immobilized onto the heparinized- Bio-$Oss^{(R)}$ surface. The release kinetics of the rhBMP-2-Bio-$Oss^{(R)}$ and heparinized rhBMP-2-Bio-$Oss^{(R)}$ were analyzed using an enzyme-linked immunosorbent assay. The biological activities of the MG63 cells on the three groups were investigated via cytotoxicity assay, cell proliferation assay, alkaline phosphatase (ALP) measurement, and calcium deposition determination. Statistical comparisons were carried out by one-way ANOVA test. Differences were considered statistically significant at $^*$P<.05 and $^{**}$P<.001. RESULTS. The heparinized rhBMP-2-Bio-$Oss^{(R)}$ showed more sustained release compared to the rhBMP-2-Bio-$Oss^{(R)}$ over an extended time. In the measurement of the ALP activity, the heparinized group showed a significantly higher ALP activity when compared with the non-heparinized groups (P<.05). The MG63 cells cultivated in the group with rhBMP-2 showed increased calcium deposition, and the MG63 cells from the heparinized group increased more than those that were cultivated in the non-heparinized groups. CONCLUSION. Heparin increased the rhBMP-2 release amount and made sustained release possible, and heparinized Bio-$Oss^{(R)}$ with rhBMP-2 successfully improved the osteoblastic functions.

• The Journal of the Korean dental association
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• v.53 no.1
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• pp.6-13
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• 2015

A new field in dental implantology is developing with the goal of finding new ways to improve the osteoconductivity of bone substitutes and to study new molecules able to dictate cellular differentiation and improve bone regeneration. The real future in bone regeneration seems to be in connection with the rhBMP-2s, currently obtained by synthesis using recombinant DNA. Since the first rhBMP-2 studies in humans by Boyne, There are many studies for bone regeneration at oral and maxillofacial area. The rhBMP-2 is widely used at sinus augmentation, alveolar bone defect, and socket preservation.

• Journal of Microbiology and Biotechnology
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• v.24 no.2
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• pp.188-196
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• 2014

Extracellular production of recombinant human bone morphogenetic protein-7 (rhBMP-7) was carried out through the fermentation of Bacillus subtilis. Three significant fermentation conditions and medium components were selected and optimized to enhance the rhBMP-7 production by using the response surface methodology (RSM). The optimum values of the three variables for the maximum extracellular production of rhBMP-7 were found to be 2.93 g/l starch, 5.18 g/l lactose, and a fermentation time of 34.57 h. The statistical optimization model was validated with a few fermentations of B. subtilis in shake flasks under optimized and unoptimized conditions. A 3-L jar fermenter using the shake-flask optimized conditions resulted in a higher production (413 pg/ml of culture medium) of rhBMP-7 than in a shake flask (289.1 pg/ml), which could be attributed to the pH being controlled at 6.0 and constant agitation of 400 rpm with aeration of 1 vvm.

• Journal of Veterinary Clinics
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• v.39 no.6
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• pp.302-310
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• 2022

Recently, in human medicine and veterinary medicine, interest in synthetic bone graft is increasing. Among them, bone morphogenic protein (BMP) is currently being actively researched and applied to clinical trials. However, BMP has the disadvantage of being expensive and easily absorbed into surrounding tissues. Therefore, BMP requires the use of small amounts and rhBMP (recombinant human bone morphogenetic protein)-2 carriers that can be released slowly. Hydrogel has the property of swelling a large amount of water inside when it is aqueous solution, and when it is, it consists of more than 90 percent water. Using these properties, hydrogels are often used as rhBMP-2 carrier. The scaffold used in this study is a hydrogel made from which keratin is extracted using human hair and based on it. In this study, we wanted to see the effect of bone formation in the calvarial defect model by using keratin-based hydrogel made with human hair as a scaffold. The experiment was conducted by dividing 3 groups a total of 12 mice. Calvarial bone defect is set to all 4 mm diameters. Bone formation was evaluated by using gross evaluation, micro-computed tomography (micro-CT), immunohistochemistry. Groups using keratin-based hydrogel were significantly observed compared to Group 1s, and the most bone formations were found when rhBMP-2 and hydrogel were used. This represents the superiority of the functions of the rhBMP-2 carrier by a new material, keratin-based hydrogel. Through gross evaluation, micro-CT, and immunohistochemistry, we can confirm that keratin-based hydrogel is a useful rhBMP-2 carrier.

• Journal of Periodontal and Implant Science
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• v.38 no.2
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• pp.125-134
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• 2008

Purpose: Bone morphogenetic protein (BMP) is a potent differentiating agent for cells of the osteoblastic lineage. It has been used in the oral cavity under a variety of indications and with different carriers. However, the optimal carrier for each indication is not known. This study evaluated the bone regenerative effect of rhBMP-2 delivered with different carrier systems. Materials and Methods: 8 mm critical-sized rat calvarial defects were used in 60 male Sprague-Dawley rats. The animals were divided into 6 groups containing 10 animals each. Two groups were controls that had no treatment and absorbable collagen membrane only. 4 groups were experimentals that contained rhBMP-2 only and applied with absorbable collagen sponge($Collatape^{(R)}$), $MBCP^{(R)}$, Bio-$Oss^{(R)}$ each. The histological and histometric parameters were used to evaluate the defects after 2- or 8-week healing period. The shape and total augmented area were stable in all groups over the healing time. Results: New bone formation was significantly greater in the rhBMP-2 with carrier group than control group. rhBMP-2/ACS was the highest in bone density but gained less new bone area than rhBMP-2/$MBCP^{(R)}$ and rhBMP-2/Bio-$Oss^{(R)}$. The bone density after 8 weeks was greater than that after 2 weeks in all groups. However, rhBMP-2 alone failed to show the statistically significant difference in new bone area and bone density compared to control group. Also $MBCP^{(R)}$ and Bio-$Oss^{(R)}$ particles remained after 8 weeks healing period. Conclusion: These results suggest that rhBMP-2 with carrier system is an excellent inductive agent for bone formation and we can use it as the predictable bone tissue engieering technique. Future study will likely focus on the kinetics of BMP release and development of carriers that is ideal for it.

• Journal of Periodontal and Implant Science
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• v.38 no.sup2
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• pp.355-362
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• 2008

Purpose: The carrier for the delivery of bone morphogenetic proteins(BMPs) should also serve as a scaffold for new bone growth. In addition, predictable bone formation in terms of the volume and shape should be guaranteed. This study evaluated the ectopic bone formation of recombinant human BMP-2(rhBMP-2) using a micro macroporous biphasic calcium phosphate (MBCP: mixture of ${\beta}TCP$ and HA) block as a carrier in a rat subcutaneous assay model. Materials and Methods: Subcutaneous pockets were created on the back of 40 male Sprague-Dawley rats. In the pockets, rhBMP-2/MBCP and MBCP alone were implanted. The blocks were evaluated by histological and histometric parameters after a healing interval of 2 weeks (each 10 rats; MBCP and rhBMP-2/MBCP) or 8 weeks (each 10 rats; MBCP and rhBMP-2/MBCP). Results: The shape and volume of the block was maintained stable over the healing period. No histological bone forming activity was observed in the MBCP alone sites after 2 weeks and there was minimal new bone formation at 8 weeks. In the rhBMP-2/MBCP sites, new bone formation was evident in the macropores of the block. The new bone area at 8 weeks was greater than at 2 weeks. There was a further increase in the quantity of new bone with the more advanced stage of remodeling. Conclusions: A MBCP block could serve as a carrier system for predictable bone tissue engineering using rhBMPs.