• Proceedings of the Polymer Society of Korea Conference
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• 2006.10a
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• pp.264-264
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• 2006

The nanoparticle-hydrogel complex as a new bone defect replacement matrix, which is composed of the nanoparticles for the sustained release of BMP and the hydrogel for filling the bone defect site and playing a role as a matrix where new bone can grow, is presented. In vivo evaluation of bone formation was characterized by soft X-ray, MT staining, and calcium assay, based on the rat calvarial critical size defect model. The effective bone regeneration was achieved by the BMP-2 loaded nanoparticles in fibrin gel, compare to bare fibrin gel, the nanoparticle-fibrin gel complex without BMP-2, or the BMP-2 in fibrin gel, in terms of the new bone area and the gray level in X-ray, the bone marrow are, and the calcium content in the initial defect site. These findings suggest that the BMP-2 loaded nanoparticle-fibrin gel complex can a promising candidate for a new bone defect replacement matrix.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• v.26 no.2
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• pp.179-185
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• 2000

The purpose of this study was to develop an osteogenic, biodegradable material using polymer and BMP. It was designed to have structural function and be moldable, for the reconstruction of load bearing areas and deformities of various configurations. Bone apatite was added to Poly(L-lactide)(PLLA) and made porous for osteoconductability and ease of BMP loading. The materials, with or without BMP purified from porcine bone matrix, were evaluated in cranial bone defect models in rats for biocompatibility and bone regeneration capability. The following results were obtained: The PLLA-BMP material with BMP added to the polymer showed 30% healing of cranial bone defects in rats during the 2 weeks to 3 months period of observation. The moldable PLLA agent without BMP also showed 25% bone healing capacity. Although new bone formation was incomplete in the critical size defect of rat cranium, it can be concluded that the unique moldability of those agents makes them useful for the reconstruction of various bone defects and maxillofacial deformities.

• Tissue Engineering and Regenerative Medicine
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• v.19
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• pp.1099-1111
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• 2022

Background: Bone marrow-derived mesenchymal stem cells (BMSCs) and bone morphogenetic protein-2 (BMP-2) have been studied for bone repair because they have regenerative potential to differentiate into osteoblasts. The development of injectable and in situ three-dimensional (3D) scaffolds to proliferate and differentiate BMSCs and deliver BMP-2 is a crucial technology in BMSC-based tissue engineering. Methods: The proliferation of mouse BMSCs (mBMSCs) in collagen/poly-γ-glutamic acid (Col/γ-PGA) hydrogel was evaluated using LIVE/DEAD and acridine orange and propidium iodide assays. In vitro osteogenic differentiation and the gene expression level of Col/γ-PGA(mBMSC/BMP-2) were assessed by alizarin red S staining and quantitative reverse-transcription polymerase chain reaction. The bone regeneration effect of Col/γ-PGA(mBMSC/BMP-2) was evaluated in a mouse calvarial bone defect model. The cranial bones of the mice were monitored by micro-computed tomography and histological analysis. Results: The developed Col/γ-PGA hydrogel showed low viscosity below ambient temperature, while it provided a high elastic modulus and viscous modulus at body temperature. After gelation, the Col/γ-PGA hydrogel showed a 3D and interconnected porous structure, which helped the effective proliferation of BMSCs with BMP-2. The Col/γ-PGA (mBMSC/BMP-2) expressed more osteogenic genes and showed effective orthotopic bone formation in a mouse model with a critical-sized bone defect in only 3-4 weeks. Conclusion: The Col/γ-PGA(mBMSC/BMP-2) hydrogel was suggested to be a promising platform by combining collagen as a major component of the extracellular matrix and γ-PGA as a viscosity reducer for easy handling at room temperature in BMSC-based bone tissue engineering scaffolds.

• Journal of Periodontal and Implant Science
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• v.37 no.4
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• pp.733-742
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• 2007

Bone morphogenetic proteins have been shown to possess significant osteoinSductive potential, but in order to take advantage of this effect for tissue engineering, carrier systems are essential. Successful carrier systems must enable vascular and cellular invasion, allowing BMP to act as a differentiation factor. The carrier should be reproducible, non-immunogenic, moldable, and space-providing, to define the contours of the resulting bone. The purpose of this study was to review available literature, in comparing various carriers of BMP on rat calvarial defect model. The following conclusions were deduced. 1. Bone regeneration of ACS/BMP, ${\beta}-TCP/BMP$, FFSS/BMP, $FFSS/{\beta}-TCP/BMP$, MBCP/BMP group were significantly greater than the control groups. 2. Bone density in the ACS/BMP group was greater than that in ${\beta}-TCP$, FFSS, $FFSS/{\beta}-TCP$ carrier group. 3. Bone regeneration in FFSS/BMP group was less than in ACS/BMP, ${\beta}-TCP/BMP$, MBCP/BMP group. However, New bone area of $FFSS/{\beta}-TCP/BMP$ carrier group were more greater than that of FFSS/BMP group. ACS, ${\beta}-TCP$, FFSS, $FFSS/{\beta}-TCP$, MBCP were used for carrier of BMP. However, an ideal carrier which was reproducible, non-immunogenic, moldable, and space-providing did not exist. Therefore, further investigation are required in developing a new carrier system.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.4
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• pp.1183-1186
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• 2012

Objective: To observe the effect of insulin-like growth factor-1 (IGF-1) on bone morphogenetic protein (BMP)-2 expression in hepatocellular carcinoma SMMC7721 cells. Methods: Cells were divided into blank control, IGF-1, IGF-1 + SB203580, and SB203580 groups. SB203580 was used to block the p38 MAPK signaling pathway. Changes in the expression of BMP-2, p38 MAPK, and phosphorylated p38, MERK, ERK and JNK were determined using reverse transcription polymerase chain reactions (RT-PCR) and Western blot analysis. Results: Protein expression of phosphorylated BMP-2, MERK, ERK, and JNK was significantly up-regulated by IGF-1 compared with the control group ($1.138{\pm}0.065$ vs. $0.606{\pm}0.013$, $0.292{\pm}0.005$ vs. $0.150{\pm}0.081$, $0.378{\pm}0.006$ vs. $0.606{\pm}0.013$, and $0.299{\pm}0.015$ vs. $0.196{\pm}0.017$, respectively; P<0.05). Levels of BMP-2 and phosphorylated MERK and JNK were significantly reduced after blocking of the p38MAPK signaling pathway ($0.494{\pm}0.052$ vs. $0.165{\pm}0.017$, $0.073{\pm}0.07$ vs. $0.150{\pm}0.081$, and $0.018{\pm}0.008$ vs. $0.196{\pm}0.017$, respectively; P<0.05), but such a significant difference was not observed for phosphorylated ERK protein expression ($0.173{\pm}0.07$ vs. $0.150{\pm}0.081$, P>0.05). Conclusion: IGF-1 can up-regulate BMP-2 expression, and p38 MAPK signaling pathway blockage can noticeably reduce the up-regulated expression. We can conclude that the up-regulatory effect of IGF-1 on BMP-2 expression is realized through the p38 MAPK signaling pathway.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• v.34 no.1
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• pp.49-58
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• 2008

Objective: The Purpose of the study was to investigate the bone morphogenic protein expression of rhBMP-2(recombinant human bone morphogenic protein-2) as singnaling molecule and ${\beta}-TCP$(Tricalcium phosphate) as a bone substitute and carrier medium of rhBMP-2. Materials and Methods: 16 rabbits divided into 2 group of each 8 rabbit. Two standardized bone defect, round bilateral defect was made in the cranium of the 8 rabbit of first group, and was grafted with $150{\sim}500{\mu}m$ diameter ${\beta}-TCP$ 0.25g in one side, which was soaked with rhBMP-2, and autogenous bone was grafted on another side as a positive control. Second group of 8 rabbit, only ${\beta}-TCP$ was grafted with same size and same manner. After 2, 4, 8, and 12 weeks, specimen was taken for microscopic immunohiostochemical and histomorphometric analysis. Result: Grafting ${\beta}-TCP$ with rhBMP show the early formation of the bone regenerative factor (BMP-4) and more quantity of new bone formation than only use of ${\beta}-TCP$ (8,12 week), even show less new bone formation than autogenous bone. Conclusion : The experimental study result that ${\beta}-TCP$ graft combination with rhBMP-2 as a delivery system is an effective with osteoinductive capacity and biodegradable properties, so that provide clinical availibility of composite use in reconstruction of bony defect.

• Maxillofacial Plastic and Reconstructive Surgery
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• v.29 no.6
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• pp.467-473
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• 2007

The most important factor for successful implantation is osseointegration between the implant and bone. The expression of bone morphogenetic proteins (BMPs) inducing bone formation would differ after maxillary sinus elevation. And within the same graft material. the expression of BMPs would change with time after graft. The aim of this study was to compare the relative expressions of BMP4 and BMP6 using real-time RT-PCR when maxillary sinus elevation was performed using deproteinated bovine bone powder (DBBP) as the graft material or absorbable gelatin sponge (AGS) as the filler without any graft material. Fifteen rabbits, each weighing between 3.0 to 3.5 Kg, were divided randomly into 5 groups of 3 animals each based on their time of sacrifice 0, 3, 5, 7 and 9 days). After exposure of the maxillary sinus bilaterally, bone graft was performed in the right maxillary sinus using DBBP ($BBP^{(R)}$ Oct Inc., Cheonan, Korea) and only AGS ($Gelfoam^{(R)}$ Pharmacia & Upjohn Company, Kalamazoo, MI, U.S.A) was placed into the left without any graft material. Each group of rabbits was sacrificed at 1, 3, 5, 7, or 9 days after operation and all specimens were harvested. And the following results were obtained using real-time RT-PCR from isolated total RNA of the samples. 1. The expression of BMP4 increased at postoperative 1 and 3 days in both DBBP group and AGS group. In AGS group. it decreased at postoperative 5 days. increased again at postoperative 7 days, and decreased at postoperative 9 days. In DBBP group, it increased until postoperative 7 days and decreased at postoperative 9 days. Although the expression of BMP4 was higher in DBBP group compared with AGS group, it was not statistically significant (p>0.05). 2. The expression of BMP6 increased at postoperative 1 and 3 days in both DBBP group and AGS group. In AGS group, it decreased at postoperative 5 days, increased again at postoperative 7 days, and decreased at postoperative 9 days. In DBBP group, it increased until postoperative 7 days and decreased at postoperative 9 days. Although the expression of BMP6 was higher in AGS group compared with DBBP group, it was not statistically significant (p>0.05). 3. There was no statistically significant difference in BMP expression in both groups during same period of time. It' s probably because DBBP and AGS both functioned as a space retainer so that the BMP expression in blood clot seemed to be similar. 4. Thus, DBBP would not offer many benefits for early bone regeneration compared with AGS. The expression of BMP in early bone formation seems to be more influenced by physical carrier rather than the graft type.

• BMB Reports
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• v.42 no.2
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• pp.86-90
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• 2009

Deletion of smpd3 induces osteogenesis and dentinogenesis imperfecta in mice. smpd3 is highly elevated in the parietal bones of developing mouse calvaria, but not in sutural mesenchymes. Here, we examine the mechanism of smpd3 regulation, which involves BMP2 stimulation of Runx2. smpd3 mRNA expression increased in response to BMP2 treatment and Runx2 transfection in C2C12 cells. The Runx2-responsive element (RRE) encoded within the -562 to -557 region is important for activation of the smpd3 promoter by Runx2. Electrophoretic mobility shift assays revealed that Runx2 binds strongly to the -355 to -350 RRE and less strongly to the -562 to -557 site. Thus, the smpd3 promoter is activated by BMP2 and is directly regulated by the Runx2 transcription factor. This novel description of smpd3 regulation will aid further studies of bone development and osteogenesis.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• v.30 no.4
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• pp.282-291
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• 2004

Pure-phase beta-tricalcium phosphate(${\beta}$-TCP) proved to be a bone regeneration material, providing the patient with vital bone at the defect site in a reasonable time, making a second surgical procedure for bone harvesting unnecessary. This study compares bone healing and BMP 2/4 expression in cranial defects in rabbits grafted with autogenous bone and ${\beta}$-TCP. Thirty New Zealand White rabbits was divided into 3 group of 10 animals each. Bilateral calvarial defects were made in the parietal bones of each animal. ${\beta}$-TCP placed in one defect and the other defects was filled with autogenous bone. The animal were sacrificed at 4, 8 and 12 weeks. Immunohistochemical analysis was used to investigate the expression of BMP 2/4. 1. The new bone formation around autogenous bone from 4 weeks and ${\beta}$-TCP from 8 weeks. 2. In autogenous bone graft, BMP 2/4 expression was decreased from 4 to 12 weeks. 3. In ${\beta}$-TCP graft, BMP 4 expression was increased from 8 to 12 weeks. But, BMP 2 was observed from 12 weeks. This study showed that bone healing, regeneration and, BMP 2/4 expression are delayed in grafted ${\beta}$-TCP than autogenous bone.

• The Journal of the Korean dental association
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• v.53 no.1
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• pp.28-35
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• 2015

To overcome shortcoming of autogeneous, allogenic, xenogenic and alloplastic bone grafts, various growth factors related to bone regeneration have been identified and developed. Among them, rhBMP-2 is regarded as the most potent osteoinductive growth factor and it can trigger the differentiation of mesenchymal stem cells to osteogenic cells for accelerated new bone formation And several commercial products of rhBMP-2 are available in Korea. It is applied to maxillary sinus augmentation, guided bone regeneration and preservation of extraction socket. In this review, the development, action mechanism and clinical applications of rhBMP-2 will be described.