• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• v.45 no.3
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• pp.123-128
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• 2019

Demineralized dentin matrix (DDM) has been used as a recombinant human bone morphogenetic protein-2 (rhBMP-2) carrier in many clinical trials. To optimize the clinical safety and efficacy of rhBMP-2 with DDM, efforts have been made to improve the delivery of rhBMP-2 by 1) lowering the administered dose, 2) localizing the protein, and 3) prolonging its retention time at the action site as well as the bone forming capacity of the carrier itself. The release profile of rhBMP-2 that is associated with endogenous BMP in dentin has been postulated according to the type of incorporation, which is attributed to the loosened interfibrillar space and nanoporous dentinal tubule pores. Physically adsorbed and modified, physically entrapped rhBMP-2 is sequentially released from the DDM surface during the early stage of implantation. As DDM degradation progresses, the loosened interfibrillar space and enlarged dentinal tubules release the entrapped rhBMP-2. Finally, the endogenous BMP in dentin is released with osteoclastic dentin resorption. According to the postulated release profile, DDM can therefore be used in a controlled manner as a sequential delivery scaffold for rhBMP-2, thus sustaining the rhBMP-2 concentration for a prolonged period due to localization. In addition, we attempted to determine how to lower the rhBMP-2 concentration to 0.2 mg/mL, which is lower than the approved 1.5 mg/mL.

• Journal of Korean Neurosurgical Society
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• v.65 no.6
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• pp.825-833
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• 2022

Objective : ABM/P-15 (anorganic bone matrix/15-amino acid peptide fragment) is a commercially available synthetically manufactured P-15 collagen peptide fragment, that is adsorbed on ABM. This study was done to investigate the efficacy of ABM/P-15 in achieving fusion in the lumbar spine and comparing it with that of recombinant bone morphogenic protein-2 (rhBMP-2) and demineralized bone matrix (DBM). Methods : A retrospective observational study of prospectively collected data of 140 patients who underwent lumbar spinal fusion surgeries in a single specialty spine hospital between 2016 and 2020, with a minimum 6-month follow-up was conducted. Based on the material used for the augmentation of the bone graft at the fusion site, the patients were divided into three categories namely ABM/P-15, rhBMP-2, and DBM group. Results : ABM/P-15, rhBMP-2, and DBM were used in 46, 44, and 50 patients, respectively. Patient characteristics like age, gender, bone mineral density, smoking history, and presence of diabetes mellitus were comparable amongst the three groups. Average follow-up was 16.0±5.2, 17.9±9.8, and 26.2±14.9 months, respectively in ABM/P-15, rhBMP-2, and DBM groups. The fusion was achieved in 97.9%, 93.2%, and 98% patients while the average time-to-union was 4.05±2.01, 10±4.28, and 9.44±3.49 months (p<0.001), respectively for ABM/P-15, rhBMP-2, and DBM groups. The average pre-operative Visual analogue scale score was 6.93±2.42, 7.14±1.97, 7.01±2.14 (p=0.900) for ABM/P-15, rhBMP-2 and DBM groups, respectively, which reduced to 1.02±0.80, 1.21±0.96, and 0.54±0.70 (p=0.112), respectively at the last follow up. Pre-operative Oswestry disability index scores were 52.7±18.02, 55.4±16.8, and 53.56±19.6 (p=0.751) in ABM/P-15, rhBMP-2, and DBM groups, which post-operatively reduced to 33.77±15.52, 39.42±16.47, and 38.3±15.89 (p=0.412) and further to 15.74±8.3, 17.41±10.45, and 16.76±9.81 (p=0.603), respectively at the last follow-up. Conclusion : ABM/P-15 appears to achieve union significantly earlier than rhBMP-2 and DBM in lumbar spinal fusion cases while maintaining a comparable clinical and complication profile.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• v.31 no.6
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• pp.481-491
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• 2005

Purpose: The aim of the present study is to evaluate the effect of autogenous bone and allograft material coverd with a bioresorbable membrane on bone regeneration after a simultaneous installation of implant. Materials and methods: Twelve healthy rabbits, weighing about $3{\sim}4$ kg, were used in this experiment. Following impalnt(with 3.25 mm diameter and 8 mm length) site preparation by surgical protocol of $Oraltronics^{(R)}$, artificial bony defect, 5mm sized in height and depth, was created on femoral condyle using trephine drill(with 5 mm diameter and 5 mm length). Then implant was inserted. In the experimental group A, the bony defect was filled with autogenous particulated bone and coverd with $Lyoplant^{(R)}$ resorbable membrane. In the experimental group B, the bony defect was filled with allograft material(Orthoblast $II^{(R)}$) containing demineralized bone matrix and covered with $Lyoplant^{(R)}$. In the control group, without any graft materials, the bony defect was covered with $Lyoplant^{(R)}$. The experimental group A and B were divided into each 9 cases and control group into 3 cases. The experimental animals were sacrificed at 3, 6 and 8 weeks after surgery and block specimens were obtained. With histologic and histomorphometric analysis, we observed the histologic changes of the cells and bone formation after H-E staining and then, measured BIC and bone density with KAPPA Image $Base^{(R)}$ system. Results: As a result of this experiment, bone formation and active remodeling process were examined in all experimental groups and the control. But, the ability of bone formation of the experimental group A was somewhat better than any other groups. Especially bone to-implant contact fraction ranged from 12.7% to 43.45% in the autogenous bone group and from 9.02% to 29.83% in DBM group, at 3 and 8 weeks. But, bone density ranged from 15.67% to 23.17% in the autogenous bone group and from 25.95% to 46.06% in DBM group at 3 and 6 weeks, respectively. Although the bone density of DBM group was better than that of autogenous bone group at 3 and 6weeks, the latter was better than the former at 8 weeks, 54.3% and 45.1%, respectively. Therefore these results showed that DBM enhanced the density of newly formed bone at least initially.

• 대한치주과학회:학술대회논문집
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• 2002.05a
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• pp.20-20
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• 2002

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• v.42 no.2
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• pp.90-98
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• 2016

Objectives: The aim of this study was to compare the osteogenic effects of demineralized dentin matrix (DDM) combined with recombinant human bone morphogenetic protein-2 (rhBMP-2) in rabbit calvarial defects with DDM and anorganic bovine bone (ABB) combined with rhBMP-2. Materials and Methods: Four round defects with 8-mm diameters were created in each rabbit calvaria. Each defect was treated with one of the following: 1) DDM, 2) ABB/rhBMP-2, or 3) DDM/rhBMP-2. The rhBMP-2 was combined with DDM and ABB according to a stepwise dry and dip lyophilizing protocol. Histological and microcomputed tomography (${\mu}CT$) analyses were performed to measure the amount of bone formation and bone volume after 2- and 8-week healing intervals. Results: Upon histological observation at two weeks, the DDM and ABB/rhBMP-2 groups showed osteoconductive bone formation, while the DDM/rhBMP-2 group showed osteoconductive and osteoinductive bone formation. New bone formation was higher in DDM/rhBMP-2, DDM and ABB decreasing order. The amounts of bone formation were very similar at two weeks; however, at eight weeks, the DDM/rhBMP-2 group showed a twofold greater amount of bone formation compared to the DDM and ABB/rhBMP-2 groups. The ${\mu}CT$ analysis showed markedly increased bone volume in the DDM/rhBMP-2 group at eight weeks compared with that of the DDM group. Notably, there was a slight decrease in bone volume in the ABB/rhBMP-2 group at eight weeks. There were no significant differences among the DDM, ABB/rhBMP-2, and DDM/rhBMP-2 groups at two or eight weeks. Conclusion: Within the limitations of this study, DDM appears to be a suitable carrier for rhBMP-2 in orthotopic sites.

• Journal of Periodontal and Implant Science
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• v.31 no.1
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• pp.57-74
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• 2001

The purpose of this study was to evaluate the adjunctive combined effect of demineralized freeze-dried bone allograft(DFDB) in guided bone regeneration on supra-alveo-lar peri-implant defect. Supra-alveolar perio-implant defects, 3mm in height, each including 4 IMZ titanium plasma-sprayed implants were surgically created in two mongrel dogs. Subsequently, the defects were treated with 1 of the following 3 modalities: Control) no membrane or graft application, Group1) DFDB application, Group2) guided bone regeneration using an expanded polytetra-fluoroethylene membrane, Group3) guided bone regeneration using membrane and DFDB. After a healing period of 12-week, the animals were sacrificed, tissue blocks were harvested and prepared for histological analysis. Histologic examination were as follows; 1. New bon formation was minimal in control and Group 1, but considerable new bone formation was observed in Group 2 and Group 3. 2. There was no osteointegration at the implant-bone interface in the high-polished area of group2 and Group 3. 3. In fluorescent microscopic examination, remodeling of new bone was most active during week 4 and week 8. There was no significant difference in remodeling rate between group 2 and group 3. 4. DFDB particles were observed, invested in a connective tissue matrix. Osteoblast activity in the area was minimal. The results suggest that guided bone regeneration shows promising results in supra-alveolar peri-implant defects during the 12 week healing period although it has a limited potential in promoting alveolar bone regeneration in the high-polished area. There seems to be no significant adjunctive effect when DFDB is combined with GBR.

• Archives of Plastic Surgery
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• v.35 no.6
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• pp.631-636
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• 2008

Purpose: Adipose tissue-derived stem cells(ADSC) has an osteoconductive potential and demineralized bone matrix(DBM) is an osteoinductive material. A combination of DBM and ADSC wound probably create osteoinductive properties. The purpose of this study is to determine the effect of the combination of DBM and ADSC mixture on healing of rat calvarial defect. Methods: Thirty adult male Sprague-Dawley rats were randomized into 3 groups(n=10) as 1) Control, 2) DBM alone, 3) DBM with ADSC mixture. DBM with ADSC mixture group has had a 3-day preculture of ADSC from groin fat pad. An 6 mm critical size circular calvarial defect was made in each rat. Defect was implanted with DBM alone or DBM with ADSC mixture. Control defect was left unfilled. 6 and 12 weeks after the implantation, the rats were sacrificed and the defects were evaluated by histomorphometric and radiographical studies. Results: Histomorphometric analysis revealed that DBM with ADSC mixture group showed significantly higher bone formation than DBM alone group(p<0.05). Although radiographs from DBM alone group and DBM with ADSC group revealed similar diffuse radiopaque spots dispersed throughout the defect. Densitometric analysis of calvarial defect revealed DBM with ADSC mixture group significantly higher bone formation than DBM alone(p<0.05). There was correlation of densitometry with new bone formation(Spearman's correlation of coefficient=0.804, 6 weeks, 0.802, 12 weeks). Conclusion: The DBM with ADSC mixture group showed the best healing response and the osteoinductive properties of DBM were accelerated with ADSC mixture. It will be clinically applicable that DBM and ADSC mixture in plastic and reconstructive surgery, such as alveolar cleft and congenital facial deformities that bone graft should be required.

• 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 the Korean Association of Oral and Maxillofacial Surgeons
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• v.27 no.6
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• pp.491-497
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• 2001

Polymethylmethacrylate(PMMA) is currently commonly used material for the reconstruction of bone defects and fixation of joint prosthetics following congenital and acquired causes. Although PMMA has widespread use, it does not possess the ideal mechanical characteristics with osteoconductivity and osteoinductivity required. In order to overcome these problem, addition of bovine bone drived defatting demineralized bone(BDB) powders to a PMMA bone cement was done for improvement of physical property and bone forming characteristics of composite. In order to investigate the influence of BDB reinforcement on the PMMA, we measured physical property of compressive, tensile, flexural strength, and scanning electron microscopic examinations. The results were obtained as follows: 1. The PMMA forms a solid cellular matrix with open cells about $100{\mu}m$ in variable size and incorporating BDB. BDB aggregates inside the cells form a porous network that is accessible from the outer surface. 2. The physical properties were compressive strength of mean $22.74{\pm}1.69MPa$, tensile strength of mean $22.74{\pm}1.69MPa$, flexural strength of mean $77.53{\pm}6.93MPa$. Scanning electron microscopic examinations were revealed that there was DBD particles form a highly porous agglomerates. BDB can be added PMMA in the form of dried powders, the composites are applicable as bone substitutes. BDB and PMMA mixture is shown to produce a class of composites that due to their microstructure and improved mechanical properties may be suitable for application as bone subsitutes. The mechanical and material properties of the BDB-PMMA bone substitute composites are competitive with those properties of a porous ceramic matrix of other hydroxyapatite and with those of natural bones.

• Journal of Veterinary Clinics
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• v.27 no.2
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• pp.147-153
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• 2010

Bio-integration of cartilage grafts with subchondral bone is a significant clinical challenge. To date, the use of demineralized bone matrix (DBM) has been one of the most effective strategies for bone cell proliferation in vivo. Here, we investigated whether coculture of chondrocytes and DBM could serve as a single-platform system containing all the essential elements for purposive bone and cartilage induction. The aim of this study was to evaluate and compare the phenotype and proliferation of bovine chondrocytes cocultured with DBM in two different culture systems, pellet and alginate bead culture. In alginate bead culture, we observed an increase in chondrocyte number and formation of cell clusters. Typical chondrocytic phenotype was maintained for entire eight weeks. Histological analysis showed that chondrocytes maintained a typical round, plump morphology and there was a gradual increase in lacunae. Both coculture systems yielded an expanded cell population as compared to the controls (chondrocytes alone). The production of glycosaminoglycans was also increased in the coculture systems as compared to controls.