Enhanced Bone Regeneration in Variable-Type Biphasic Ceramic Phosphate Scaffolds Using rhBMP-2

Our aim was to investigate the bone regeneration capacity of powder-type biphasic ceramic scaffold (BCP powder), block-type BCP (BCP block), and collagen-added block-type BCP (BCP collagen) with different concentrations of recombinant human bone morphogenetic protein 2 (rhBMP-2) in an animal model. Four rabbits were assigned to each of the following groups: no graft + rhBMP-2 (0.1/0.2 mg/mL), BCP powder + rhBMP-2 (0.1/0.2 mg/mL), BCP block + rhBMP-2 (0.1/0.2 mg/mL), and BCP collagen + rhBMP-2 (0.1/0.2 mg/mL), i.e., a total of 32 rabbits. Polycarbonate tubes (Φ 7 mm × 5 mm) for supporting scaffolds were fixed into a 7 mm round border. Subsequently, 0.1 mL of rhBMP-2 solutions with different concentrations was injected into the tubes. Both radiological and histomorphometric analyses showed that osteogenesis was not enhanced by increasing the concentration of rhBMP-2 in all groups at both 3 and 6 weeks. Radiological analysis showed that bone formation was higher in the BCP collagen group than in the BCP powder and BCP block groups at both rhBMP-2 concentrations at 3 weeks. rhBMP-2 enhanced bone formation; however, as the concentration increased, bone formation could not be enhanced infinitely. Collagen-added alloplastic graft material may be useful for mediating rapid bone formation in initial stages.

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Bone Regeneration Using a Three-Dimensional Hexahedron Channeled BCP Block Combined with Bone Morphogenic Protein-2 in Rat Calvarial Defects

Materials ◽

10.3390/ma12152435 ◽

2019 ◽

Vol 12 (15) ◽

pp. 2435 ◽

Cited By ~ 3

Author(s):

So-Yeun Kim ◽

Eun-Bin Bae ◽

Jae-Woong Huh ◽

Jong-Ju Ahn ◽

Hyun-Young Bae ◽

...

Keyword(s):

Bone Regeneration ◽

Alveolar Bone ◽

Three Dimensional ◽

Bone Morphogenetic Protein 2 ◽

Graft Material ◽

Implant Placement ◽

Morphogenetic Protein ◽

Human Bone Morphogenetic Protein ◽

Calvarial Defects ◽

Rat Calvarial Defect

It is important to obtain sufficient bone mass before implant placement on alveolar bone, and synthetic bone such as biphasic calcium phosphate (BCP) has been studied to secure this. This study used a BCP block bone with a specific structure of the three-dimensional (3D) hexahedron channel and coating with recombinant human bone morphogenetic protein-2 (rhBMP-2) impregnated carboxymethyl cellulose (CMC) was used to examine the enhancement of bone regeneration of this biomaterial in rat calvarial defect. After the preparation of critical-size calvarial defects in fifteen rats, defects were divided into three groups and were implanted with the assigned specimen (n = 5): Boneplant (untreated 3D hexahedron channeled BCP block), Boneplant/CMC (3D hexahedron channeled BCP block coated with CMC), and Boneplant/CMC/BMP (3D hexahedron channeled BCP block coated with CMC containing rhBMP-2). After 4 weeks, the volumetric, histologic, and histometric analyses were conducted to measure the newly formed bone. Histologically, defects in the Boneplant/CMC/BMP group were almost completely filled with new bone compared to the Boneplant and Boneplant/CMC groups. The new bone volume (P < 0.05) and area (P < 0.001) in the Boneplant/CMC/BMP group (20.12% ± 2.17, 33.79% ± 3.66) were much greater than those in the Boneplant (10.77% ± 4.8, 16.48% ± 9.11) and Boneplant/CMC (10.72% ± 3.29, 16.57% ± 8.94) groups, respectively. In conclusion, the 3D hexahedron channeled BCP block adapted rhBMP-2 with carrier CMC showed high possibility as an effective bone graft material.

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Effect of recombinant human bone morphogenetic protein–2 on bone regeneration in large defects of the growing canine skull after dura mater replacement with a dura mater substitute

Journal of Neurosurgery ◽

10.3171/2009.1.jns08976 ◽

2010 ◽

Vol 112 (2) ◽

pp. 319-328 ◽

Cited By ~ 17

Author(s):

Dongmei He ◽

David G. Genecov ◽

Morley Herbert ◽

Raul Barcelo ◽

Mohammed E. Elsalanty ◽

...

Keyword(s):

Bone Formation ◽

Bone Regeneration ◽

Dura Mater ◽

Collagen Sponge ◽

Bone Morphogenetic Protein 2 ◽

Skull Defect ◽

New Bone Formation ◽

Morphogenetic Protein ◽

Human Bone Morphogenetic Protein ◽

Recombinant Human Bone

Object This study was designed to evaluate the bone regeneration potential of the dura mater and dura mater substitute (Durepair) in the presence of recombinant human bone morphogenetic protein–2 (rhBMP-2) delivered in a collagen sponge–collagen-ceramic matrix (CCM; MasterGraft Matrix) in a large skull defect in growing canines. Methods Forty immature male beagles were used to create two 2.5 × 4–cm cranial defects on each side of the sagittal suture. The dura mater on the left side was cut to make a 1 × 3–cm defect and replaced with bovine skin collagen (Durepair). The dura mater on the right side remained intact. Different doses of rhBMP-2 (none [8 animals], 0.11 mg/ml [4 animals], 0.21 mg/ml [4 animals], and 0.43 mg/ml [8 animals]) were infused on 2 Type I bovine absorbable collagen sponge (ACS) strips. The strips were layered with the CCM (15% hydroxyapatite [HA]/85% tricalcium phosphate [TCP]) to reconstruct both cranial defects. In a fifth group (8 animals), 0.43 mg/ml rhBMP-2 was directly infused into the CCM. Demineralized canine cancellous freeze-dried demineralized bone matrix (DBM; 8 animals) was used as a control in a sixth group. All materials were fixed under 2 resorbable protective sheets (MacroPore). Skulls were resected 16 weeks after operation. Histological and histomorphometric analyses on the percentage of the defect spanned by bone, and the percentage of residual HA-TCP granules and collagen were analyzed. Results Calcified seroma was the only complication observed and only occurred in the 0.43-mg/ml rhBMP-2 groups (Groups 4 and 5). Dura mater repair appeared complete at 4 months in all animals. New bone was formed sporadically throughout the skull defect in the ACS+CCM and DBM groups without rhBMP-2. In all rhBMP-2 groups, mature new bone (compact and trabecular) was uniformly formed across the defect on both the repaired and intact dura mater sides. There was significant new compact bone formation on top of the repaired dura mater, which did not appear in the ACS+CCM and DBM groups lacking rhBMP-2. Greater HA-TCP and collagen scaffold resorption was noted in rhBMP-2 groups compared with non–rhBMP-2 groups. Statistical analysis showed there was a significantly lower percentage of bone spanning the defect in the ACS+CCM group compared with groups with rhBMP-2, with more residual HA-TCP and collagen on the repaired dura mater side than the intact dura mater side (p < 0.05). In all rhBMP-2 groups, there were no significant differences in new bone formation between the repaired and intact dura mater sides (p > 0.05). Conclusions The ACS+CCM combination had an effect similar to demineralized bone-on-bone regeneration in craniofacial reconstruction. The addition of rhBMP-2 to CCM directly or with ACS induces mature new bone formation in large cranial defects both in the presence of intact dura mater and repaired dura mater.

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Induction of bone formation by Escherichia coli-expressed recombinant human bone morphogenetic protein-2 using block-type macroporous biphasic calcium phosphate in orthotopic and ectopic rat models

Journal of Periodontal Research ◽

10.1111/j.1600-0765.2011.01390.x ◽

2011 ◽

Vol 46 (6) ◽

pp. 682-690 ◽

Cited By ~ 21

Author(s):

J-C. Park ◽

S-S. So ◽

I-H. Jung ◽

J-H. Yun ◽

S-H. Choi ◽

...

Keyword(s):

Escherichia Coli ◽

Calcium Phosphate ◽

Bone Formation ◽

Biphasic Calcium Phosphate ◽

Bone Morphogenetic Protein 2 ◽

Block Type ◽

Rat Models ◽

Morphogenetic Protein ◽

Human Bone Morphogenetic Protein ◽

Recombinant Human Bone

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Phosphate graphene as an intrinsically osteoinductive scaffold for stem cell-driven bone regeneration

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.1815434116 ◽

2019 ◽

Vol 116 (11) ◽

pp. 4855-4860 ◽

Cited By ~ 23

Author(s):

Anne M. Arnold ◽

Brian D. Holt ◽

Leila Daneshmandi ◽

Cato T. Laurencin ◽

Stefanie A. Sydlik

Keyword(s):

Bone Formation ◽

Bone Regeneration ◽

Bone Cells ◽

Standard Of Care ◽

Ectopic Bone Formation ◽

Bone Morphogenetic Protein 2 ◽

Ectopic Bone ◽

Human Bone Morphogenetic Protein

Synthetic, resorbable scaffolds for bone regeneration have potential to transform the clinical standard of care. Here, we demonstrate that functional graphenic materials (FGMs) could serve as an osteoinductive scaffold: recruiting native cells to the site of injury and promoting differentiation into bone cells. By invoking a Lewis acid-catalyzed Arbuzov reaction, we are able to functionalize graphene oxide (GO) to produce phosphate graphenes (PGs) with unprecedented control of functional group density, mechanical properties, and counterion identity. In aqueous environments, PGs release inducerons, including Ca2+ and PO43−. Calcium phosphate graphene (CaPG) intrinsically induces osteogenesis in vitro and in the presence of bone marrow stromal cells (BMSCs), can induce ectopic bone formation in vivo. Additionally, an FGM can be made by noncovalently loading GO with the growth factor recombinant human bone morphogenetic protein 2 (rhBMP-2), producing a scaffold that induces ectopic bone formation with or without BMSCs. The FGMs reported here are intrinsically inductive scaffolds with significant potential to revolutionize the regeneration of bone.

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The Bone Regeneration Capacity of BMP-2 + MMP-10 Loaded Scaffolds Depends on the Tissue Status

Pharmaceutics ◽

10.3390/pharmaceutics13070979 ◽

2021 ◽

Vol 13 (7) ◽

pp. 979

Author(s):

Patricia Garcia-Garcia ◽

Ricardo Reyes ◽

José Antonio Rodriguez ◽

Tomas Martín ◽

Carmen Evora ◽

...

Keyword(s):

Bone Formation ◽

Bone Regeneration ◽

Growth Promotion ◽

Tissue Growth ◽

Bone Morphogenetic Protein 2 ◽

Morphogenetic Protein ◽

Therapeutic Molecules ◽

Positive Effect

Biomaterials-mediated bone formation in osteoporosis (OP) is challenging as it requires tissue growth promotion and adequate mineralization. Based on our previous findings, the development of scaffolds combining bone morphogenetic protein 2 (BMP-2) and matrix metalloproteinase 10 (MMP-10) shows promise for OP management. To test our hypothesis, scaffolds containing BMP-2 + MMP-10 at variable ratios or BMP-2 + Alendronate (ALD) were prepared. Systems were characterized and tested in vitro on healthy and OP mesenchymal stem cells and in vivo bone formation was studied on healthy and OP animals. Therapeutic molecules were efficiently encapsulated into PLGA microspheres and embedded into chitosan foams. The use of PLGA (poly(lactic-co-glycolic acid)) microspheres as therapeutic molecule reservoirs allowed them to achieve an in vitro and in vivo controlled release. A beneficial effect on the alkaline phosphatase activity of non-OP cells was observed for both combinations when compared with BMP-2 alone. This effect was not detected on OP cells where all treatments promoted a similar increase in ALP activity compared with control. The in vivo results indicated a positive effect of the BMP-2 + MMP-10 combination at both of the doses tested on tissue repair for OP mice while it had the opposite effect on non-OP animals. This fact can be explained by the scaffold’s slow-release rate and degradation that could be beneficial for delayed bone regeneration conditions but had the reverse effect on healthy animals. Therefore, the development of adequate scaffolds for bone regeneration requires consideration of the tissue catabolic/anabolic balance to obtain biomaterials with degradation/release behaviors suited for the existing tissue status.

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