Bone augmentation by recombinant human BMP-2 and biologically active glass of calvaria on adult rabbit
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Objective: To study the effect of BAG on bone induced by recombinant human bone morphogenetic protein-2 and to evaluate the bone regenerative potential of rhBMP-2 on adult domestic rabbits calvarial bone. Methods: 16 adult rabbits were devided into 4 groups. Tight subperiosteal pockets were created on adult rabbit calvarial bone and implanted with various grafts: rhBMP-2/BAG, BAG, rhBMP-2 and no implant as control group. Evaluations consist clinical examinations, histology and histomorphometry. Results: rhBMP-2 /BAG induced bone formation by mean of intramembranous bone tormation. The new bone combined directly to host bone. At the 2,4 and 8 weeks post-operation, the width of new bone formated in group rhBMP-2/BAG was significantly larger than group BAG (P0.05), and the bone tomation in group BAG was larger than the rest two groups. Conclusions: BAG has good conductibility and absorbability. rhBMP-2/BAG can promote bone angmentation in calvaria and is a promising bone substitute in clinical applications.Keywords:
Calvaria
Bone Formation
Intramembranous ossification
Human bone
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The purpose of this study was to determine whether bone augmentation could be obtained by the composite of recombinant human bone morphogenetic protein-2 (rhBMP-2) and bioabsorbable atelocollagen when the periosteum was resected, and to compare the efficacy of the rhBMP-2/collagen implant and the collagen alone implant. The onlay implant was inserted into the space between the elevated galea aponeurotica and the skull without the periosteum of 10-month-old rats. The rhBMP-2/collagen implant resulted in osteoblasts differentiation under the galea at 1 week and active bone formation without a prior formation of cartilage. At 4 weeks, the bony trabeculae were interconnected and connected directly with the compact bone of the skull. Histomorphometric analysis at 4 weeks demonstrated that the rhBMP-2/collagen implant showed 92.5% in the volume of bone tissue, whereas the collagen alone showed 0%. The implanted collagen was gradually replaced by bone tissue in the presence of rhBMP-2. Our present results indicate that rhBMP-2 stimulates undifferentiated mesenchymal cells in the galea overlying the implant to proliferate and differentiate directly into osteoblasts on the carrier collagen fibers. The collagen matrix was stably placed on the skull and suitable as a substitute for rhBMP-2. The rhBMP-2/collagen onlay implant might be clinically applicable for bone augmentation even under the condition without the periosteum.
Periosteum
Galea
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We aimed to evaluate the efficacy of demineralized dentin matrix (DDM) fixed with recombinant human bone morphogenetic protein-2 (rhBMP-2) through an experimental and a clinical study. Unilateral upper second and third premolars of eight beagles were extracted. A mucoperiosteal flap was elevated around the extraction socket, and a bone defect was made using a surgical drill. Each DDM was fixed with rhBMP-2, and autogenous bone was grafted at the bone defect area with a collagenous membrane. The beagles were euthanized at two, four, eight, and 12 weeks after receiving the bone graft. Block specimens involving grafted bone and surrounding natural bone were extracted. A total of 23 patients who received bone grafts using human DDM fixed with rhBMP-2 (AutoBT BMP) with implant placements (36 implants; maxilla: 14, mandible: 22) were selected. The implant stability, marginal bone loss, and clinical outcome were evaluated. Three trephine cores were harvested fourmonths after bone grafting, and histologic examination was performed. In the histological evaluation performed four weeks after the bone graft, autogenous bone showed 52% new bone formation and DDM fixed with rhBMP-2 showed 33% new bone formation. Twelve weeks after the bone graft, autogenous bone showed 75% new bone formation and DDM fixed with rhBMP-2 showed 48% new bone formation. In the clinical study, favorable osseointegration was obtained in 35 out of 36 implant sites (one case of osseointegration failure). In all cases, severe complications were not observed. Histomorphometrically, new bone formation was observed in 14.98% of the cases. The residual DDM particles were 6.22%. AutoBT BMP provides good osteoinductive and osteoconductive potential and clinical efficacy.
Trephine
Bone grafting
Mandible (arthropod mouthpart)
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Summary Objectives: To determine whether the addition of recombinant human bone morphogenetic protein (rhBMP-2) to a self-crosslinkable cellulosic hydrogel/biphasic calcium phosphate (BCP) granules construct promotes bone healing in critical-size ulnar defects in dogs. Methods: A standardized 2 cm long ulnar ostectomy was performed bilaterally in five dogs to compare bone healing with hydrogel/BCP constructs associated with or without rhBMP-2. Cancellous-bone autografts were used as positive controls in unilateral ulnar defects in five additional dogs. Radiographically, bone healing was evaluated at four, eight, 12, 16 and 20 weeks postoperatively. Histological qualitative analysis with microCT imaging and light and scanning electron microscopy were performed 20 weeks after implantation. Results: All rhBMP-2-loaded constructs induced the formation of well-differentiated mineralized lamellar bone surrounding the BCP granules and bridging bone/implant interfaces as early as eight weeks after surgery. Bone regeneration appeared to develop earlier with the rhBMP-2 constructs than with the cancellous-bone autografts while similar results were obtained at 20 weeks. Constructs without any rhBMP-2 showed osteoconductive properties limited to the bone junctions and a lack of osteoinduction without bone ingrowth within the implantation site. In one dog, the leakage of the hydrogel loaded with rhBMP-2 induced an extensive heterotopic bone formation. Clinical significance: The addition of rhBMP-2 to a self-crosslinkable hydrogel/BCP construct could promote bone regeneration in a critical-size-defect model with similar performance to autologous bone grafts.
Ostectomy
Cancellous bone
Endochondral ossification
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Bone Formation
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Abstract Objectives The purpose of this study was to compare the effects of rhBMP2 with rhBMP9 on ridge augmentation following healing of extraction sockets in dogs. Material and methods Five male Beagle dogs, approximately 12 months of age, were used. The mesial roots of the four maxillary premolars were endodontically treated. The distal roots were extracted, and the buccal bony walls removed. All extraction sockets were filled with deproteinized bovine bone mineral (DBBM). A collagen membrane was soaked with 4 μg or 20 μg of rhBMP9, 20 μg of rhBMP2 or sterile saline and placed over the augmented sites. All animals were euthanized after 8 weeks of healing and investigated by micro‐CT and histologic analysis. A one‐way ANOVA with Tukey's HSD post hoc test was used to compare the differences between the four groups. Results New bone apposition in all defects was observed from the original bone. RhBMP samples showed an increase in bone formation in the buccal area and better integration of DBBM particles when compared to control sites. Both rhBMP9 defects showed higher values of bone ( p = 0.024), bone marrow ( p = 0.044), and total augmentation volume ( p = 0.033) than the rhBMP2 (20 μg) or control sites. Highest bone area was found in rhBMP9 defects ( p = 0.895). Conclusions Within the limitations of the present study, rhBMP9 sites demonstrated higher bone‐inducing potential in combination with DBBM than rhBMP2. While rhBMP9s failed to demonstrate a clear dose‐response relationship to the outcomes, future studies are necessary to evaluate the appropriate dose and carrier systems.
Beagle
Apposition
X-ray microtomography
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Abstract This study aimed to quantify the healing following vertical augmentation of allogenic bone blocks with/without recombinant human bone morphogenetic protein‐2 (rhBMP‐2) on rabbit calvaria. Experiments were performed using allogenic bone blocks which were grafted bilaterally with or without rhBMP‐2 on 20 rabbit calvaria, and these animals were divided to four groups according to the use of rhBMP‐2 and healing periods (2 and 8 weeks; n = 10 in each group). Onlay‐type bone blocks (8 mm in diameter and 5 mm high) were fixed with a self‐tapping screw after removing the cortex in the control group, and the same protocol was applied with the addition of soaking the bone blocks with rhBMP‐2 for 15 min in the test group. Radiographic and histologic analyses were performed after 2 or 8 weeks to evaluate the volumetric stability and bone regeneration within the grafted area. The radiographic analysis revealed that the height of the allogenic bone block decreased but its volume was maintained from 2 to 8 weeks in both the control and test groups. The histologic results demonstrated a statistically significant increase in new bone area in the test group, especially in the lower region adjacent to the preexisting calvarial floor. The amount of newly formed bone in all regions of the augmented bone blocks in both the control and test groups was greater at 8 weeks than at 2 weeks. In conclusion, the vertically grafted allogenic bone block maintained its volume with new bone formation, and this was accelerated by the addition of rhBMP‐2. These findings indicate that allogenic bone block soaked with rhBMP‐2 could be a useful candidate biomaterial for vertical augmentation. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 106B: 2700–2707, 2018.
Calvaria
Bone Formation
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Objective To induce mandibular bone regeneration and repairing of bone defects using the rhBMP carrier system compounded with BMSc and to evaluate their osteogenic activities.Methods The BMSc were seeded onto absorbable polylactic acid compounded with rhBMP, and then the composite was implanted into the mandibular bone defect. The effect of new bone formation was evaluated by radiography, histology, biochemical examinations of Alkaline phosphatase in 4 and 8 weeks after operation. The new bone was weighted in 8 weeks of postoperation to compare the activity of bone formation.Results In the experimental groups with PLA/rhBMP/BMSc, the activity and new bone quantity were significantly higher than that in group B, C, and D and the single control group(P0.01). Similarly,in the group B and C,the activity and new bone quantity were significantly higher than that in group D and the single control group(P0.01).Conclusion PLA/rhBMP/BMSc demonstrate positive activity in inducing mandibular bone cells regeneration and may be used as an effective material for mandibular bone defect reconstruction.
Polylactic Acid
Histology
Bone Formation
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Background: A major challenge for dental implantology is to consistently obtain appropriate bone augmentation before implant placement. The aim of this study is to evaluate the effect of recombinant human bone morphogenetic protein 2 (rhBMP‐2) associated with bone substitute materials beta‐tricalcium phosphate (β‐TCP), biphasic calcium phosphate (BCP), and bovine bone mineral on vertical guided bone regeneration (GBR) in rabbit calvarium. Methods: Four titanium cylinders were fixed to the calvarium of 22 rabbits. In group 1 (n = 10), three cylinders were randomly filled with one of the test materials, and one cylinder was filled with a blood clot (CL). In group 2 (n = 12), the cylinders were randomly assigned to the same materials and CL but with the addition of rhBMP‐2. Bone labels were injected over the course of 13 weeks, and euthanasia was performed 14 weeks after surgery in both groups. Results: The mean volume and area of tissue growth was greater in group 2 (with rhBMP‐2) than in group 1 (without rhBMP‐2), irrespective of the material used ( P <0.001). The mean volume of tissue growth in the CL cylinder was smaller than that observed with all other materials ( P <0.001) in both groups. The mean area of regenerated bone in the CL cylinder was smaller than that observed in the β‐TCP cylinder ( P = 0.028). The histologic study revealed more lamellar bone in the rhBMP‐2 group, with a greater level of biodegradation of all the bone substitute materials tested. Conclusion: The use of rhBMP‐2/absorbable collagen sponge (ACS) combined with all of the bone substitute materials tested resulted in a greater amount of bone formation than that produced with the bone substitute materials alone or rhBMP‐2/(ACS) and CL using the rabbit calvarium GBR model.
Human bone
Rabbit (cipher)
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Citations (34)
To investigate new bone (NB) formation by using bone-block substitute materials with/without recombinant human bone morphogenetic protein-2 (rhBMP-2).Three synthetic bone-block substitute materials [biphasic calcium phosphate (BCP); nanostructured hydroxyapatite (NH); 3D-printed tricalcium phosphate/hydroxyapatite (3DP)] and one xenogeneic deproteinized bovine bone mineral (DBBM) block substitute were affixed to rabbit calvarium using osteosynthesis screws, either with rhBMP-2 (n = 12) or without rhBMP-2 (n = 16). At 2 or 12 weeks (n = 6 with rhBMP-2 and n = 8 without rhBMP-2 for each week), histologic, histomorphometric and microcomputed tomography analyses were performed.The application of rhBMP-2 increased NB formation in all experimental groups at both weeks. DBBM resulted in a greater area of NB compared with synthetic blocks either with or without rhBMP-2 at 2 weeks (2.8 ± 0.9 vs. 1.4 ± 0.5-1.9 ± 1.4 mm2 ; 1.4 ± 1.0 vs. 0.6 ± 0.3-0.9 ± 0.5 mm2 ) and without rhBMP-2 at 12 weeks (3.0 ± 0.8 vs. 1.7 ± 0.7-2.6 ± 1.5 mm2 ) (p > 0.05). NB formation did not differ significantly for DBBM and the three types of synthetic block with rhBMP-2 at 12 weeks (4.5 ± 2.0 vs. 3.8 ± 0.7-5.1 ± 1.1 mm2 ; p > 0.05).rhBMP-2 enhanced NB in all blocks. DBBM blocks yielded more NB than synthetic blocks without rhBMP-2. The application of rhBMP-2 appears to compensate for differences in late healing.
Human bone
Rabbit (cipher)
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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 β-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 150~500㎛ diameter β-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 β-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 β-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 β-TCP (8,12 week), even show less new bone formation than autogenous bone. Conclusion : The experimental study result that β-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.
Bone grafting
Rabbit (cipher)
Bone Formation
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