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Yoo H.-S.,Pusan National University | Bae J.-H.,Pusan National University | Kim S.-E.,Chonnam National University | Bae E.-B.,Pusan National University | And 5 more authors.
Materials | Year: 2017

In this study, bisphasic calcium phosphate (BCP) and two types of polysaccharide, carboxymethyl cellulose (CMC) and hyaluronic acid (HyA), were used to fabricate composite block bone grafts, and their physical and biological features and performances were compared and evaluated in vitro and in vivo. Specimens of the following were prepared as 6 mm diameter, 2 mm thick discs; BPC mixed with CMC (the BCP/CMC group), BCP mixed with crosslinked CMC (the BCP/c-CMC group) and BCP mixed with HyA (the BCP/HyA group) and a control group (specimens were prepared using particle type BCP). A scanning electron microscope study, a compressive strength analysis, and a cytotoxicity assessment were conducted. Graft materials were implanted in each of four circular defects of 6 mm diameter in calvarial bone in seven rabbits. Animals were sacrificed after four weeks for micro-CT and histomorphometric analyses, and the findings obtained were used to calculate new bone volumes (mm3) and area percentages (%). It was found that these two values were significantly higher in the BCP/c-CMC group than in the other three groups (p < 0.05). Within the limitations of this study, BCP composite block bone graft material incorporating crosslinked CMC has potential utility when bone augmentation is needed. © 2017 by the authors.


Huh J.-B.,Korea University | Park C.-K.,Korea University | Kim S.-E.,Chonnam National University | Shim K.-M.,Nambu University | And 4 more authors.
Oral Surgery, Oral Medicine, Oral Pathology, Oral Radiology and Endodontology | Year: 2011

Objective. The aim of this study was to examine the effect of Escherichia coli-derived recombinant human bone morphogenetic protein 2 (ErhBMP-2) coated onto anodized implant to stimulate local bone formation, including osseointegration and the vertical augmentation of the alveolar ridge. Study design. Six young male adult beagle dogs were used. A crestal area was leveled on both sides of each test subject by removing minimal cortical bone using a round bur and without exposing cancellous bone. After a 2-month healing period, 3 anodized implants (length 8 mm, diameter 4 mm; Cowellmedi, Busan, Korea) were placed 5 mm into the mandibular alveolar ridge in either side. Each animal received 6 implants that were either coated with ErhBMP-2 (0.75 or 1.5 mg/mL concentration; Cowellmedi) or uncoated. This was performed using a randomized split-mouth design. A total of 36 implants were used for this study. Twelve noncoated implants were used as control, and 24 BMP-coated implants were used as our experimental group, which was further divided into 2 groups of 12 implants each with different BMP concentration of 0.75 and 1.5 mg/mL. Radiologic examinations were performed immediately after implant placement and 4 and 8 weeks after implant placement. The amount of bone augmentation was evaluated by measuring the distance from the uppermost point of the cover screw to the marginal bone. Implant stability quotient (ISQ) values were measured immediately after surgery and 8 weeks after implant placement. Statistical analysis was performed using one-way analysis of variance (SPSS version 17.0) and multiple-comparison tests. Statistical significance was established at the 95% confidence level. Results. Implants coated with ErhBMP-2 at 0.75 mg/mL (BMP 0.75 group) and 1.5 mg/mL (BMP 1.5 group) exhibited significant vertical bone formation compared with the control group (mean ± SD): 0.88 ± 0.94 versus 0.60 ± 0.64 versus -0.52 ± 0.64 mm, respectively; P < .05. There was a significant difference between the 3 groups in bone level change (P < .05). The BMP 0.75 and BMP 1.5 groups exhibited significant changes in ISQ compared with the control group: 8.17 ± 8.31 versus 11.50 ± 9.02 versus 2.17 ± 7.61, respectively; P < .05. Conclusion. Within the limits of this study, the ErhBMP-2 coating on an anodized implant may stimulate vertical bone augmentation, which significantly increases implant stability on completely healed alveolar ridges. © 2011 Mosby, Inc. All rights reserved.


Huh J.-B.,Pusan National University | Kim S.-E.,Korea University | Kim H.-E.,Korea University | Kang S.-S.,Chonnam National University | And 4 more authors.
International Journal of Oral and Maxillofacial Surgery | Year: 2012

This study evaluated the effects of Escherichia coli-derived rhBMP-2 (ErhBMP-2) coated onto anodized implants to stimulate bone formation, osseointegration and vertical bone growth in a vertical bone defect model. Six young adult beagle dogs were used. After a 2-month bone healing period, anodized titanium implants (8 mm in length) were placed 5.5 mm into the mandibular alveolar ridge. Eighteen implants coated with ErhBMP-2 (BMP group) and another 18 uncoated implants (control group) were installed using a randomized split-mouth design. The implant stability quotient (ISQ) values were measured. Specimens were fabricated for histometric analysis to evaluate osseointegration and bone formation. The ISQ values at 8 weeks after implant placement were significantly higher in the BMP group than in the control group (p < 0.05). Histological observations showed that the changes in bucco-lingual alveolar bone levels were higher in the BMP group than in the control group (p < 0.05). The ErhBMP-2 coated anodized implants can stimulate bone formation and increase implant stability significantly on completely healed alveolar ridges in dogs. Further studies evaluating the effects of ErhBMP-2 on osseointegration in the bone-implant interface are warranted. © 2012 International Association of Oral and Maxillofacial Surgeons.


Kim J.-E.,Korea University | Kang S.-S.,Chonnam National University | Choi K.-H.,Cowellmedi Co. | Shim J.-S.,Pusan National University | And 3 more authors.
Oral Surgery, Oral Medicine, Oral Pathology and Oral Radiology | Year: 2013

Objectives: The aim of this study was to evaluate the effect of anodized implants coated with combined rhBMP-2 and recombinant human vascular endothelial growth factors (rhVEGFs) on vertical bone regeneration in the marginal portion of the peri-implant. Study Design: Supra-alveolar defects were created in 3 male beagle dogs. Each animal received 8 implants that were either coated with a single growth factor (rhBMP-2) or combined growth factors (rhBMP-2 + rhVEGF), or an anodized implant (the control group). The amount of the vertical bone regeneration, the bone-implant contact, and the intrathread bone density were investigated using histomorphometric analysis at 8 weeks. Results: The bone morphogenetic protein (BMP) group and the BMP-VEGF group showed vertical alveolar bone regeneration and enhanced bone-implant contact in the microthread compared with the control group (P <.05). Conclusions: Anodized implants coated with rhBMP-2 and rhBMP - 2 + rhVEGF can induce vertical alveolar bone regeneration, but the combined effect of rhBMP-2 and rhVEGF was not verified. © 2013 Elsevier Inc. All rights reserved.


Lee J.-H.,Hangang Secred Heart Hospital | Kim C.-S.,Research Institute for Periodontal Regeneration | Choi K.-H.,Cowellmedi Co. | Jung U.-W.,Research Institute for Periodontal Regeneration | And 3 more authors.
Biomaterials | Year: 2010

We investigated the ability of recombinant human bone morphogenetic protein-2, produced from Escherichia coli (ErhBMP-2), to form orthotopic and ectopic bone in rat models. BMP-2 was expressed in E. coli and extracted from the inclusion bodies. Critical-sized calvarial defects and subcutaneous pouches were created in rats, and an absorbable collagen sponge (ACS) was loaded with different doses of ErhBMP-2 for implantation. ACS alone and sham surgery controls were also included. Implant sites were evaluated by histological and/or histometric analyses following a 2- or 8-week healing interval. In the calvarial defect model, enhanced bone formation was observed with all doses of ErhBMP-2, while only limited amounts of new bone were found in controls. In the ectopic subcutaneous implant model, bone formation was clearly observed in all animals treated with ErhBMP-2 at 2 weeks. However, at 8 weeks, less new bone formation was detected than at 2 weeks. Nevertheless, the remaining new bone showed an advanced degree of bone remodeling and more maturity than that observed at 2 weeks. These results showed that ErhBMP-2 was osteoinductive under controlled in vivo conditions. Thus, ErhBMP-2 has definite potential as an alternative to rhBMP-2 produced in a eukaryotic system for clinical use. © 2010 Elsevier Ltd. All rights reserved.


Kim S.E.,Korea University | Yun Y.-P.,Korea University | Song H.-R.,Korea University | Choi K.-H.,Cowellmedi Co. | And 3 more authors.
International Journal of Pediatric Otorhinolaryngology | Year: 2013

Objective: The aim of the study was to analyze the value of Escherichia coli-derived recombinant human bone morphogenetic protein-2 (ErhBMP-2) coated biphasic calcium phosphate (BCP) for the obliteration of middle ear bone defect after mastoid surgery. Methods: Twenty-four specific pathogen-free Sprague-Dawley rats were randomly assigned to the BCP group ( n= 12) and BCP-ErhBMP-2 group ( n= 12; in which BCP scaffold of the granular type was coated with ErhBMP-2). In both groups, BCP scaffold was used to surgically fill the middle ear bulla. New bone formation was evaluated by measuring bone density (%) after 4 and 8 weeks in all rats in both groups. Results: At 4 weeks, new bone was visible at the periphery and center of the middle ear cavity in both groups. In the BCP group, a moderate amount of fibrous tissue had infiltrated into the interspace of the scaffolds. New bone almost totally filled the interspace in the BCP-ErhBMP-2 group. At 8 weeks, copious new bone formation had occurred. Histometric measurements showed that bone density in the BCP group was smaller than in the BCP-ErhBMP-2 group at 4 weeks (25.10% and 38.43%, respectively; p<. 0.05) and 8 weeks (25.54% and 34.18%, respectively; p<. 0.05). Conclusions: New bone formation was greater in the presence of BCP-ErhBMP-2 scaffolds. ErhBMP-2 coated BCP scaffolds is a potentially useful material for middle ear obliteration after mastoidectomy. © 2013 Elsevier Ireland Ltd.


Huh J.-B.,Pusan National University | Yang J.-J.,Korea University | Choi K.-H.,Cowellmedi Co. | Bae J.H.,Pusan National University | And 3 more authors.
International Journal of Molecular Sciences | Year: 2015

Anorganic bovine bone matrix (Bio-Oss®) has been used for a long time for bone graft regeneration, but has poor osteoinductive capability. The use of recombinant human bone morphogenetic protein-2 (rhBMP-2) has been suggested to overcome this limitation of Bio-Oss®. In the present study, heparin-mediated rhBMP-2 was combined with Bio-Oss® in animal experiments to investigate bone formation performance; heparin was used to control rhBMP-2 release. Two calvarial defects (8 mm diameter) were formed in a white rabbit model and then implanted or not (controls) with Bio-Oss® or BMP-2/Bio-Oss®. The Bio-Oss® and BMP-2/Bio-Oss® groups had significantly greater new bone areas (expressed as percentages of augmented areas) than the non-implanted controls at four and eight weeks after surgery, and the BMP-2/Bio-Oss® group (16.50 ± 2.87 (n = 6)) had significantly greater new bone areas than the Bio-Oss® group (9.43 ± 3.73 (n = 6)) at four weeks. These findings suggest that rhBMP-2 treated heparinized Bio-Oss® markedly enhances bone regeneration. © 2015 by the authors; licensee MDPI, Basel, Switzerland.


Hanseler P.,University of Zürich | Jung U.-W.,Yonsei University | Jung R.E.,University of Zürich | Choi K.-H.,Cowellmedi Co. | And 3 more authors.
Acta Biomaterialia | Year: 2012

Bone morphogenetic proteins (BMP), in particular BMP-2, are the growth factors primarily responsible for osteoinduction. A knowledge of interactions between bone substitute materials and growth factor variants is crucial to designing bone substitutes with an ideal release profile. Here we compare glycosylated and non-glycosylated recombinant human bone morphogenetic protein-2 (rhBMP-2) either incorporated into a hydrolyzable polyethylene glycol (PEG) hydrogel developed as a slow release system or adsorbed to a deproteinized bovine bone matrix (DBBM), a clinically well-established bone substitute material. rhBMP-2 loaded materials were immersed in cell culture medium and rhBMP-2 concentration profiles in the supernatant were determined by an enzyme-linked immunosorbent assay. The corresponding biological activities were assessed in vitro by alkaline phosphatase activity assay. We show a strong affinity of rhBMP-2 for DBBM and reduced biological activity after its release from PEG hydrogels. Glycosylated rhBMP-2 was significantly less affected by the hydrogel and interacted significantly more strongly with DBBM than non-glycosylated rhBMP-2. We therefore question the combination of PEG hydrogels with DBBM as a rhBMP-2 delivery system over DBBM alone, since rhBMP-2 released from the hydrogel will be trapped by DBBM. Moreover, our results suggest that glycosylated rhBMP-2 is favorable in combination with PEG hydrogels, since its activity is better preserved, whereas in combination with DBBM non-glycosylated rhBMP-2 is favorable, benefiting from an initially higher concentration of free rhBMP-2. © 2011 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.


Trademark
Cowell Medi Co. | Date: 2010-07-13

Dental implants; bone block prostheses; artificial bone parts to be implanted in natural bones; bone forceps; bone screw; fixation devices, namely, fixation implants comprised of artificial material; artificial joints; forceps for dental technical purposes; mirrors for dentists; dental foundation supports; X-ray appliances for dental and medical use; dental burrs; broach for dental purposes; oral irrigator units for dental purposes; dental chairs; dental apparatus, namely, disposable prophy angles; electric dental apparatus, namely, intra-oral light system; cutting and grinding discs for dental applications; cut-off and abrasive wheels for dental purposes; polymerization apparatus for dental purposes; treatment beds for dental purposes; dentists armchairs; orthodontic machines and instruments; orthodontic appliances; dental instruments, namely, spacing devices; prosthetic intervertebral discs; dental implants; artificial dental implant materials; implant anchorages; pedicle screw testing systems for dental use; dental instruments, namely, insertion and extraction devices.


PubMed | Korea University, Cowellmedi Co. and Pusan National University
Type: | Journal: BioMed research international | Year: 2015

This study was conducted to evaluate effects of rhBMP-2 applied at different concentrations to sandblasted and acid etched (SLA) implants on osseointegration and bone regeneration in a bone defect of beagle dogs as pilot study using split-mouth design. Methods. For experimental groups, SLA implants were coated with different concentrations of rhBMP-2 (0.1, 0.5, and 1mg/mL). After assessment of surface characteristics and rhBMP-2 releasing profile, the experimental groups and untreated control groups (n = 6 in each group, two animals in each group) were placed in split-mouth designed animal models with buccal open defect. At 8 weeks after implant placement, implant stability quotients (ISQ) values were recorded and vertical bone height (VBH, mm), bone-to-implant contact ratio (BIC, %), and bone volume (BV, %) in the upper 3mm defect areas were measured. Results. The ISQ values were highest in the 1.0 group. Mean values of VBH (mm), BIC (%), and BV (%) were greater in the 0.5mg/mL and 1.0mg/mL groups than those in 0.1 and control groups in buccal defect areas. Conclusion. In the open defect area surrounding the SLA implant, coating with 0.5 and 1.0mg/mL concentrations of rhBMP-2 was more effective, compared with untreated group, in promoting bone regeneration and osseointegration.

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