• Journal of Periodontal and Implant Science
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• v.36 no.1
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• pp.195-210
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• 2006

The aim of this study is to evaluate the effects of combination of rhBMP-4 and chitosan, which have osteoinductive capacity, on the regeneration of bone defects in dogs. Three beagle dogs aged over one and half years and weighed about 15Kg were used in this study. Three round defects were made by trephine bur in each side of mandibles. Each defect was filled with collagen, chitosan, rhBMP-4/chitosan. The dogs were sacrificed at 1, 3 or 8 weeks postsurgery and the results were evaluated histologically. The results of this study were as follows: 1. The sign of new bone formation, rearrangement of osteoblasts was revealed adjacent of preexisted bone or around graft materials such as chitosan. 2. The descending order of groups in bone regeneration speed was the rhBMP-4/chitosan group, chitosan group, collagen group. In the combination group, new bone was regenerated more and in better quality than others. 3. The regeneration of bone was observed in the rhBMP-4/chitosan group in 3 weeks after surgery. In 8 weeks after surgery, bone regeneration was observed in all three groups, and new bone at 8th week was denser in the chitosan and rhBMP-4/chitosan group than collagen group. In conclusion, rhBMP-4 and chitosan can be applied in the bone regeneration procedures usefully. It is considered that chitosan can be a splint for the maintenance of the defect form and produce much better effect when used with good grafting material or bone morphogenetic protein.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• v.44 no.6
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• pp.259-268
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• 2018

Objectives: The purpose of this study was to evaluate the synergic effect of recombinant human bone morphogenetic protein-2 (rhBMP-2) and low-level laser therapy (LLLT) on bisphosphonate-treated osteoblasts. Materials and Methods: Human fetal osteoblast cells (hFOB 1.19) were cultured with $100{\mu}M$ alendronate. Low-level Ga-Al-As laser alone or with 100 ng/mL rhBMP-2 was then applied. Cell viability was measured with MTT assay. The expression levels of receptor activator of nuclear factor kappa-B ligand (RANKL), macrophage colony-stimulating factor (M-CSF), and osteoprotegerin (OPG) were analyzed for osteoblastic activity inducing osteoclastic activity. Collagen type and transforming growth factor beta-1 were also evaluated for bone matrix formation. Results: The results showed that rhBMP-2 and LLLT had a synergic effect on alendronate-treated osteoblasts for enhancing osteoblastic activity and bone matrix formation. Between rhBMP-2 and LLLT, rhBMP-2 exhibited a greater effect, but did not show a significant difference. Conclusion: rhBMP-2 and LLLT have synergic effects on bisphosphonate-treated osteoblasts through enhancement of osteoblastic activity and bone formation activity.

• The Journal of the Korean dental association
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• v.53 no.5
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• pp.348-359
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• 2015

Objective: The aim of this study was to determine the effect of multi-layer of a collagen membrane alone or loaded rhBMP-2 on the buccal plate for ridge preservation after tooth extraction. Material and methods: Following bilateral extraction of the maxillary 1st and 3rd premolars in five dogs, rhBMP-2 loaded collagen membrane was applied to the buccal plates at the 1st premolar and collagen membrane only was applied to the buccal plates at the 3rd premolar unilaterally. The collagen membranes applied in the experimental groups were piled into four layers. The corresponding sites of the contralateral side healed naturally. After 3months of healing, the animals were sacrificed. Radiographic and histologic analyses were performed. Results: There was no significant difference in the healing of extraction socket at both 1st and 3rd premolars. In microcomputed tomography, the widths of the residual ridge of the experimental groups were similar with the controls. Histologically, the experimental groups did not exhibit different pattern compared to the controls regardless of the addition of rhBMP-2. Conclusion: Layering of the collagen membrane with or without rhBMP-2 on the buccal plate failed to show the effectiveness in dimensional preservation of the extraction socket.

• 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.

• Imaging Science in Dentistry
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• v.34 no.1
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• pp.35-48
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• 2004

Purpose: To investigate the effect of rhBMP-2 on the healing of bone defect in the low calcium diet rat. Materials and Methods: To prepare the experimental model, control group was fed a normal diet and experimental group was fed a low calcium diet for 3 weeks. And then, 4 mm bicortical perforated bone defect was made on mandibular body of each rats. Experimental group was subdivided into two groups; experimental group 1 (rats given a low calcium diet before and after bone defect) and experimental group 2 (rats given a low calcium diet before and after bone defect with rhBMP-2 application). At 1, 3, 5 and 7 weeks after bone defect formation, the rats were terminated. The healing of bone defect was assessed by three-dimensional computerized tomography, soft x-ray radiography, and histopathological examination. Results : The wound healing of the bone defect for control group, experimental group 1, and experimental group 2 showed a increase from 3 weeks after bone defect formation. The experimental group 2 showed a more increase in healing amount than control group and experimental group 1 from 5 weeks after bone defect formation and the experimental group 2 showed a complete recovery of bone defect at 7 weeks after bone defect formation. Conclusion: The healing process of bone defect is accelerated by rhBMP-2 application in the low calcium diet rats.

• Journal of Periodontal and Implant Science
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• v.37 no.sup2
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• pp.397-407
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• 2007

골형성 유도 단백질(bone morphogenetic protein, BMP)은 성장이나, 골형성과정에서 중용한 역할을 한다고 입증되었고 그것의 운반체에 대한 연구가 이뤄져 왔다. 하지만 수직압이 존재하는 곳에서 골증대술에 적용할 수 있을 만큼 강한 공간유지능력이 있는 운반체에 대한 연구는 그리 많지 않았다. Macroporous biphasic calcium phosphate block (MBCP block)은 공간유지능력이 뛰어나며 강한 수직압을 견딜수 있는 골대체물질이다. 이 연구의 목적은 MBCP block을 골형성유도 단백질(rhBMP-2)의 운반체로 사용하여 백서 두개골 결손부에 적용하였을 때, 골 형성 효과를 평가하는 것이다. 36마리의 웅성백서에서 8mm 지름을 갖는 임계크기의 두 개부 결손을 형성하였다. 20마리씩 2개의 군으로 나누어 MBCP block만 이식한 군, MBCP block을 운반체로 사용하여 농도 0.025mg/ml rhBMP-2를 이식한 군으로 나누어 술 후 2주와 8주에 치유결과를 조직학적, 조직계측학적으로 비교 관찰 하였다. 조직계측학적 관찰 결과, rhBMP-2/MBCP block 군에서 MBCP block군에서 보다 2, 8주 모두 골밀도(bone density)가 유의성있게 증가하였다 (P<0.01). 각 군에서도 8주째가 2주째보다 골밀도가 유의성있게 증가하였다(P<0.01). 총조직 형성량 (augmented area)에서는 변화가 없었다. 이 연구 결과, 백서 두개골 결손부에서 MBCP block은 rhBMP의 운반체로 사용하였을 때 신생골 형성에 유의한 효과가 있을뿐 아니라 공간유지능력이 우수해서 수직압이 존재하는 골증대술(bone augmentation)시 rhBMP의 운반체로 가능성이 있다고 사료된다.

• Restorative Dentistry and Endodontics
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• v.25 no.2
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• pp.170-179
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• 2000

The rh-BMP-4 is a subgroup of TGF-${\beta}$ superfamily. The application of rh-BMP in alveolar bony defect was reported to new alveolar bone and new cementum formation. For minimized complications following tooth replantation, a operator must replant a tooth fast at the pertinent position. This study was to evaluate the effect of rh-BMP-4 on periodontal regeneration and root resorption following tooth replantation in rats. The 50 Sprague-Dawley rats weighting about 130gm were used in this study. The animals were divided into three groups. Group 1 ; immediate replantation after extraction : Group 2 ; replantation stored teeth extraction of first molar, the removal of periodontal ligament with collagenase, and etching with citric acid : Group 3 ; replantation stored teeth with treated rh-BMP-4 in mesial root. Experimental animals were sacrificed 3, 7, 14 days after replantation by heart infusion. The maxillae were removed, fixed, demineralized, dehydrated, infiltrated and embedded with JB-4 mixture. For light microscopic observation, 5 micron sections were cut and stained with toluidine blue. The results of this study were as follows : 1. After experimental 3 days, all groups were observed dead space between periodontum and root. 2. After experimental 7 days, group 1 and group 3 were observed filling periodontal fibers between alveolar bone and root but group 2 were not. 3. After experimental 7 days, group 3 were observed appearance of attached cementoblast like cell on root surface. Group 1 were observed regular arrangement of fibroblasts and collagen fibers at ${\times}400$ observation. 4. After experimental 14 days, all group were observed filling periodontal fibers between alveolar bone and root. Group 1 were observed normal arrangement of periodontal fibers. Group 3 were observed less abnormal arrangement of periodontal fibers. Group 2 were not observed functional normal arrangement of periodontal fibers. 5. After experimental 14 days, group 2 and 3 were observed several root resorption and irregular root surface but group 1 were not. These results suggest that the rh-BMP-4 can stimulate cementogenesis and enhance to attach collagen fibers.

• Asian Spine Journal
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• v.12 no.6
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• pp.1010-1016
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• 2018

Study Design: Retrospective cohort study. Purpose: To report on spinal fusion assessment using computed tomography (CT) after adult spinal deformity (ASD) surgery using ultra-low dose recombinant human bone morphogenetic protein 2 (RhBMP-2). Overview of Literature: The reported dose of RhBMP-2 needed for successful spinal posterolateral fusion in ASD ranges from 10 to 20 mg per spinal level. This study reports the use of ultra-low dose of RhBMP-2 (0.07 mg per facet) to achieve spinal fusion in multilevel ASD surgery. Methods: Consecutive patients who underwent ASD surgery using ultra-low dose RhBMP-2 were recruited. Routine postoperative CT analysis for spinal fusion was performed by two spine surgeons. Inter-observer agreement was calculated for facet fusion (FF) and interbody fusion (IBF) at 6 and 12 months after the procedure. Results: Six consecutive ASD patients with a mean age of 62 years (28-72 years) were examined. Each patient received a total dose of 12 mg with an average dose of $0.69{\pm}0.2mg$ (0.42-1 mg) per single FF and $1.38{\pm}0.44mg$ (0.85-2 mg) for IBF. Total 131 FF and 15 IBF were examined in the study, with 88 FFs and nine IBFs being analyzed specifically at 6 months after the surgery. FF and IBF reported by surgeons A and B at 6 months were 97.7% vs. 91.9% FF, respectively (${\kappa}=0.95$) and 100% vs. 100% IBF, respectively (${\kappa}=1$). Two patients underwent longitudinal follow-up CT at 12 months, and the FF rates reported by surgeons A and B were 100% vs. 95.8%, respectively (${\kappa}=0.96$). Five out of nine facet (56%) non-unions were identified at the cross-links. The remaining four facet pseudarthrosis were noted at 1-2 spinal levels caudal to the cross-links. At the final clinical follow-up, there was no rod breakage, deformity progression, neurological deficit, or symptom recurrence. The Oswestry Disability Index improved by an average of $32.8{\pm}6.3$, while the mental component summary of the 36-item Short-Form Health Survey improved by an average of $4.7{\pm}2.1$, and physical component summary improved by an average of $10.5{\pm}2.1$. Conclusions: To our knowledge, this is the first study to report a CT that defined 92%-98% FF and 100% IBF using the lowest reported dose of RhBMP-2 in multilevel ASD surgery. The use of ultra-low dose RhBMP-2 reduces the RhBMP-2 related complications and healthcare costs.

• Journal of Korean Neurosurgical Society
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• v.64 no.4
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• pp.562-574
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• 2021

Objective : This study is to evaluate the efficacy and safety of demineralized bone matrix (DBM) gel versus DBM gel with recombinant human bone morphogenetic protein-2 (rhBMP-2) used in transforaminal lumbar interbody fusion (TLIF). Methods : This study was designed as a prospective, multi-center, double-blind method, randomized study. All randomized subjects underwent TLIF with DBM gel with rhBMP-2 group (40 patients) as an experimental group or DBM gel group (36 patients) as a control group. Post-operative observations were performed at 12, 24, and 48 weeks. The spinal fusion rate on computed tomography scans and X-rays films, Visual analog scale pain scores, Oswestry disability index and SF-36 quality of life (QOL) scores were used for the efficacy evaluation. The incidence rate of adverse device effects (ADEs) and serious adverse device effects (SADEs) were used for safety evaluation. Results : The spinal fusion rate at 12 weeks for the DBM gel with rhBMP-2 group was higher with 73.68% compared to 58.82% for the DBM gel group. The 24 and 48 weeks were 72.22% and 82.86% for the DBM gel with rhBMP-2 group and 78.79% and 78.13%, respectively, for the DBM gel group. However, there were no significant differences between two groups in the spinal fusion rate at 12, 24, and 48 weeks post-treatment (p=0.1817, p=0.5272, p=0.6247). There was no significant difference between the two groups in the incidence rate of ADEs (p=0.3836). For ADEs in the experimental group, 'Pyrexia' (5.00%) was the most common ADE, followed by 'Hypesthesia', 'Paresthesia', 'Transient peripheral paralysis', 'Spondylitis' and 'Insomnia' (2.50%, respectively). ADEs reported in control group included 'Pyrexia', 'Chest discomfort', 'Pain', 'Osteoarthritis', 'Nephropathy toxic', 'Neurogenic bladder', 'Liver function analyses' and 'Urticaria' (2.86%, respectively). There was no significant difference between the two groups in the incidence rate of SADEs (p=0.6594). For SADE in the experimental group, ''Pyrexia' and 'Spondylitis' were 2.50%. SADE reported in the control group included 'Chest discomfort', 'Osteoarthritis' and 'Neurogenic bladder'. All SADEs described above were resolved after medical treatment. Conclusion : This study demonstrated that the spinal fusion rates of DBM gel group and DBM gel with rhBMP-2 group were not significantly different. But, this study provides knowledge regarding the earlier postoperative effect of rhBMP-2 containing DBM gel and also supports the idea that the longer term follow-up results are essential to confirm the safety and effectiveness.

• 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.