• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• v.46 no.3
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• pp.191-196
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• 2020

Objectives: Beyond the original application approved by the U.S. Food and Drug Administration, recombinant human bone morphogenetic protein-2 (rhBMP-2) is used for medication-related osteonecrosis of the jaw (MRONJ) treatment because of its bone remodeling enhancement properties. The purpose of the study was to investigate the bone formation effect of rhBMP-2/absorbable collagen sponge (ACS) in patients with MRONJ. Materials and Methods: In this retrospective cohort study, 26 female patients diagnosed with MRONJ and who underwent mandibular sequestrectomy at Ajou University Dental Hospital from 2010 to 2018 were included. The experimental group was composed of 18 patients who received rhBMP-2/ACS after sequestrectomy, while the control group was composed of 8 patients who did not receive rhBMP-2/ACS after sequestrectomy. A total dose of 0.5 mg of rhBMP-2 was used in the experimental group at a concentration of 0.5 mg/mL. Follow-up panoramic X-rays were taken immediately after the surgery and more than 6 months after the surgery. Using those X-rays, a radiographic index of bone defect area was calculated using the modified Ihan Hren method, which measures radiographic density of the normal bone and the defect site. Results: This study suggests that rhBMP-2 contributes to new bone formation. The mean radiographic index immediately after surgery and more than 6 months after the surgery for the experimental group was 68.4% and 79.8%, respectively. The mean radiographic index immediately after surgery and more than 6 months after the surgery for the control group was 73.4% and 76.7%, respectively (Wilcoxon signed rank test, P>0.05). The mean radiographic index increased 11.4% in the experimental group and 3.27% in the control group (Mann-Whitney U-test, P<0.05). Conclusion: Based on the results, use of rhBMP-2/ACS on bone defect sites after sequestrectomy could be a successful strategy for treatment of MRONJ patients.

• Journal of Periodontal and Implant Science
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• v.45 no.6
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• pp.238-246
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• 2015

Purpose: The purpose of this study was to evaluate bone formation around recombinant human bone morphogenetic protein (rhBMP-2)-coated implants placed with or without absorbable collagen sponge (ACS) in rabbit maxillary sinuses. Methods: The Schneiderian membrane was elevated and an implant was placed in 24 sinuses in 12 rabbits. The space created beneath the elevated membrane was filled with either blood (n=6) or ACS (n=6). In the rabbits in which this space was filled with blood, rhBMP-2-coated and non-coated implants were alternately placed on different sides. The resulting groups were referred to as the BC and BN groups, respectively. The AC and AN groups were produced in ACS-grafted rabbits in the same manner. Radiographic and histomorphometric analyses were performed after eight weeks of healing. Results: In micro-computed tomography analysis, the total augmented volume and new bone volume were significantly greater in the ACS-grafted sinuses than in the blood-filled sinuses (P<0.05). The histometric analysis showed that the areas of new bone and bone-to-implant contact were significantly larger in the AC group than in the AN group (P<0.05). In contrast, none of the parameters differed significantly between the BC and BN groups. Conclusions: The results of this pilot study indicate that the insertion of ACS after elevating the Schneiderian membrane, simultaneously with implant placement, can significantly increase the volume of the augmentation. However, in the present study, the rhBMP-2 coating exhibited limited effectiveness in enhancing the quantity and quality of regenerated bone.

• Maxillofacial Plastic and Reconstructive Surgery
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• v.38
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• pp.22.1-22.6
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• 2016

Background: The aim of this study is to quantitatively evaluate the effect of rhBMP-2 for repair of bone defects after cyst enucleation using the osteogenesis index (OI). Methods: Under general anesthesia, 10 patients (12 lesions) underwent oral or maxillofacial surgery for cyst enucleation. Postoperatively, 12 lesions were divided into two groups: group A (six lesions) was treated with absorbable collagen sponge (ACS) in combination with rhBMP-2, and group B (six lesions) was treated with ACS alone. After 3 months, cone-beam computed tomographic scans were obtained to measure changes in the volume of the lesions. We then calculated the OI of each group at two different Hounsfield units to determine any statistically significant difference between these two groups (Mann-Whitney U test). Results: As tested at the level of new bone, the mean OI was 72.37 % in group A and 55.08 % in group B -a statistically significant difference (p = 0.041). As tested at the level of mature bone, the mean OI was 27.47 % in group A and 18.88 % in group B, but the difference was not statistically significant (p = 0.394). Conclusions: The application of rhBMP-2 after maxillofacial cyst enucleation accelerated new bone formation in the bone defects. Thus, the use of rhBMP-2 in combination with ACS may be considered an alternative to conventional bone grafting in some patients with postoperative bone defects.

• Journal of Periodontal and Implant Science
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• v.29 no.4
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• pp.873-893
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• 1999

The ultimate goal of periodontal therapy is the regeneration of periodontal tissue and repair of function. For more than a decade there have been many efforts to develop materials and bioactive molecule(such as growth factor and differentiation factors) to promote periodontal wound healing. Among the bioactive molecules, bone morphogenetic protein(BMP) was studied for periodontal wound healing. Since Urist demonstrated that demineralized bone matrix could induce the formation of cartilage and bone in ectopic site, many studies on BMP have been reported. Among those BMPs, it was reported that rhBMP-2 enhanced the healing of bone defects in animal studies and clinical studies. However, its efficacy in periodontal regeneration, especially 1-wall intrabony defects is still unknown. The purpose of this study was to examine the effect of rhBMP-2/ACS on the epithelial migration, gingival connective tissue adhesion, cementum formation, alveolar bone regeneration in intrabony defects of dogs. Four millimeter deep and four millimeter wide 1-wall defects were surgically created in the mesial aspects of the 3rd incisors. The test group received rhBMP-2/ACS with a flap procedure and the control underwent buffer/ACS with a flap procedure. Histologic analysis after 8 weeks of healing revealed the following results: 1. The length of epithelial growth(the distance from alveolar crest to the apical end of JE) was $0.9{\pm}1.5mm$ in the control group and $1.2{\pm}1.4mm$ in the test group. There was no statistically significant difference between the two groups. 2. The length of connective tissue adhesion was $2.4{\pm}1.3mm$ in the control group and $1.2{\pm}1.1mm$ in the test group. The control group showed significantly enhanced adhesion(P<0.05). 3. The length of new cementum was $0.9{\pm}1.0mm$ in the control group and $1.7{\pm}0.8mm$ in the test group. The test group showed significantly enhanced cementum regeneration(P<0.05). 4. The length of new bone height was $1.9{\pm}0.6mm$ in the control group and $2.4{\pm}0.9mm$ in the test group. There was no statistically significant difference between the two groups. 5. The new bone area was $4.7{\pm}1.7mm^2$ in the control group and $8.0{\pm}2.0mm^2$ in the test group. The test group showed significantly enhanced bone formed area(P<0.05). 6. The new bone density was $73.0{\pm}8.6%$ in the control group and $66.6{\pm}15.3%$ in the test group. There was no statistically significant difference between the two groups. These results suggest that the use of rhBMP-2 in 1-wall intrabony defects has significant effect on new cementum and new bone formation area, but doesn't have any significant effect on the prevention of junctional epithelium migration and new bone formation height.

• Journal of Periodontal and Implant Science
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• v.39 no.1
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• pp.77-86
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• 2009

Purpose: Recombinant human bone morphogenetic protein-2(rhBMP-2) has been evaluated as potential candidates for periodontal and bone regenerative therapy. In spite of good prospects in BMP applications, there is economically unavailable for clinical use in dental area. The purpose of this study was to evaluate the osteogenic effect of rhBMP-2 produced by E.coli expression system. Materials and methods: Eight-mm critical-size calvarial defects were created in 48 male Sprague-Dawley rats. The animals were divided into 6 groups of 8 animals each. Each group received one of the following: Negative control(sham-surgery control), positive control(absorbable collagen sponge(ACS) alone) and experimental(ACS loaded with rhBMP-2). Defects were evaluated by histologic and histometric parameters following 2- and 8-week healing intervals. Results: The experimental group showed significant defect closure at 2 and 8weeks than the sham surgery and positive control groups. Moreover, the experimental group showed significantly greater new bone and augmented area than the other groups at both 2 and 8weeks. Conclusion: rhBMP-2 produced by E.coli expression system may be effective for bone regeneration.

• 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.45 no.4
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• pp.136-144
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• 2015

Purpose: The objective of this study was to comparatively assess the bone regenerative capacity of absorbable collagen sponge (ACS), biphasic calcium phosphate block (BCP) and collagenated biphasic calcium phosphate (CBCP) loaded with a low dose of recombinant human bone morphogenetic protein-2 (rhBMP-2). Methods: The CBCP was characterized by X-ray diffraction and scanning electron microscopy. In rabbit calvaria, four circular 8-mm-diameter defects were created and assigned to one of four groups: (1) blood-filled group (control), (2) rhBMP-2-soaked absorbable collagen sponge (0.05 mg/mL, 0.1 mL; CS group), (3) rhBMP-2-loaded BCP (BCP group), or (4) rhBMP-2-loaded CBCP (CBCP group). The animals were sacrificed either 2 weeks or 8 weeks postoperatively. Histological and histomorphometric analyses were performed. Results: The CBCP showed web-like collagen fibrils on and between particles. Greater dimensional stability was observed in the BCP and CBCP groups than in the control and the CS groups at 2 and 8 weeks. The new bone formation was significantly greater in the BCP and CBCP groups than in the control and CS groups at 2 weeks, but did not significantly differ among the four groups at 8 week. The CBCP group exhibited more new bone formation in the intergranular space and in the center of the defect compared to the BCP group at 2 weeks, but a similar histologic appearance was observed in both groups at 8 weeks. Conclusions: The dose of rhBMP-2 in the present study enhanced bone regeneration in the early healing period when loaded on BCP and CBCP in rabbit calvarial defects.

• Journal of Periodontal and Implant Science
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• v.37 no.3
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• pp.497-509
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• 2007

Bone morphogenetic proteins(BMPs) are regarded as members of the transforming growth $factor-{\beta}$ superfamily with characteristic features in their amino acid sequences. A number of studies have demonstrated the biologic activities of BMPs, which include the induction of cartilage and bone formation. Recently there was a attempt to overcome a limitation of mass production, and economical efficieny of rh-BMPs. The method producing PTD by using bacteria have advantages of acquiry a mass of proteins. Hences, a new treatment which deliver protein employed by protein transduction domain(PTD) has been tried. The purpose of this study was to evaluate the bone regenerative effect of TATBMP-2 and TAT-HA2-BMP-2 employed by PTD from HlV-1 TAT protein for protein translocation in the rat calvarial model. An 8mm calvarial, critical size osteotomy defect was created in each of 32 male Spraque-Dawley rats(weight $250{\sim}300g$). The animals were divided into 4 groups of 32 animals each (4 animals/group/healing interval). The defect was treated with TATBMP-2/ACS(Absorbable collagen sponge) (TATBMP-2 0.1mg/ml), TAT-HA2-BMP-2/ACS(TAT-HA2-BMP-2 0.1mg/ml), ACS alone or left untreated for surgical control(negative control). The rats were sacrificed at 2 or 8 weeks postsurgery, and the results were evaluated histologically. The results were as follows: New bone formation were not significantly greater in the TATBMP-2/ACS group relative to negative, and positive control groups. New bone was evident at the defect sites in TAT-HA2-BMP-2/ACS group relative to negative, positive control and TATBMP-2 groups. There were a little bone regeneration in TATBMP-2 groups. While, enhanced local bone formation were observed in TAT-HA2-BMP-2 group. But, The results was not the same in all rat defects. Therefore, further investigations are required to develop a method. which disperse homogenously, and adhere to target cells.

• 대한치주과학회:학술대회논문집
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• 2001.12a
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• pp.31-31
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• 2001