J Periodontal Implant Sci.  2012 Aug;42(4):119-126. 10.5051/jpis.2012.42.4.119.

Improvement of osteogenic potential of biphasic calcium phosphate bone substitute coated with two concentrations of expressed recombinant human bone morphogenetic protein 2

Affiliations
  • 1Department of Prosthodontics, Yonsei University College of Dentistry, Seoul, Korea.
  • 2Cowell R&D Institute, Cowell Medi, Busan, Korea.
  • 3Department of Dental Biomaterials and Bioengineering, Research Institute of Dental Biomaterials and Bioengineering, Yonsei University College of Dentistry, Seoul, Korea.
  • 4Department of Dental Biomaterials, Institute of Biomaterials-Implant, Wonkwang University School of Dentistry, Iksan, Korea.
  • 5Department of Periodontology, Dental Research Institute, Seoul National University School of Dentistry, Seoul, Korea. kst72@snu.ac.kr

Abstract

PURPOSE
The aim of this study was to determine whether biphasic calcium phosphate (BCP) bone substitute with two different concentrations of Escherichia coli-expressed recombinant human bone morphogenetic protein 2 (ErhBMP-2) enhances new bone formation in a standardized rabbit sinus model and to evaluate the concentration-dependent effect of ErhBMP-2.
METHODS
Standardized, 6-mm diameter defects were made bilaterally on the maxillary sinus of 20 male New Zealand white rabbits. Following removal of the circular bony windows and reflection of the sinus membrane, BCP bone substitute without coating (control group) was applied into one defect and BCP bone substitute coated with ErhBMP-2 (experimental group) was applied into the other defect for each rabbit. The experimental group was divided into 2 subgroups according to the concentration of ErhBMP-2 (0.05 and 0.5 mg/mL). The animals were allowed to heal for either 4 or 8 weeks and sections of the augmented sinus and surrounding bone were analyzed by microcomputed tomography and histologically.
RESULTS
Histologic analysis revealed signs of new bone formation in both the control and experimental groups with a statistically significant increase in bone formation in experimental group 1 (0.05 mg/mL ErhBMP-2 coating) after a 4-week healing period. However, no statistically significant difference was found between experimental group 1 and experimental group 2 (0.5 mg/mL ErhBMP-2 coating) in osteoinductive potential (P<0.05).
CONCLUSIONS
ErhBMP-2 administered using a BCP matrix significantly enhanced osteoinductive potential in a standardized rabbit sinus model. A concentration-dependent response was not found in the present study.

Keyword

Bone morphogenetic protein 2; Bone regeneration; Bone substitute; Maxillary sinus; Rabbits

MeSH Terms

Animals
Bone Morphogenetic Protein 2
Bone Morphogenetic Proteins
Bone Regeneration
Bone Substitutes
Calcium
Durapatite
Escherichia coli
Humans
Hydroxyapatites
Male
Maxillary Sinus
Membranes
Osteogenesis
Rabbits
X-Ray Microtomography
Bone Morphogenetic Protein 2
Bone Morphogenetic Proteins
Bone Substitutes
Calcium
Durapatite
Hydroxyapatites

Figure

  • Figure 1 Maxillary sinus defects in the rabbit. Standardized, bilateral, circular, transosseous windows were prepared on the maxillary sinus using a 6-mm diameter trephine bur with the pin inserted.

  • Figure 2 Schematic diagram of trephine bur (outer diameter 8.0 mm, inner diameter 6.0 mm, depth 1.5 mm).

  • Figure 3 Histologic findings of experimental group 1 (0.05 mg/mL ErhBMP-2) at 4 weeks. (A) There appeared to be a mixture of newly formed bone from the surgically created defect and newly formed bone originating from bone graft materials. Newly formed bone from the surgically created defect is shown to be more mature whereas newly formed bone from the bone graft materials is still undergoing the mineralization process (×12.5). (B) Defect margin area: The arrowheads indicate the margin of the surgically created defect. The white asterisk indicates newly formed bone assumed to have originated from the defect margin (×50). (C) The Schneiderian membrane: The black asterisk indicates newly formed bone assumed to have originated from graft materials (×50). Note that immature woven bone is evident here in contrast to mature lamellar bone as indicated by the white asterisk in Fig. 3B. (D) Middle area: Immature woven bone can be seen (×50).

  • Figure 4 Histologic findings of experimental group 1 (0.05 mg/mL ErhBMP-2) at 8 weeks. (A) When compared to the 4 week healing group, more vascularization is evident in the 8-week healing group (arrowheads). The surgically created defect was almost completely closed. The particle size of the graft materials is dramatically reduced (white asterisk). Note that mature lamellar bone (black asterisk) is evident in the newly formed bone found in between graft materials (×12.5). (B) Defect margin area: both inflammatory cells and blood vessels can be observed, as indicated by the arrows and the arrowhead, respectively. The black asterisk indicates matured lamellar bone (×50). (C) The Schneiderian membrane: The Schneiderian membrane was also thicker than that of the 4 week healing group (×50). (D) Middle area: More mature lamellar bone is identified in newly formed bone found in between the graft materials (×50).

  • Figure 5 Histologic findings of experimental group 2 (0.5 mg/mL ErhBMP-2) at 4 weeks. (A) The histologic findings were similar to those observed in experimental group 1 (0.05 mg/mL ErhBMP-2) at 4 weeks. Note that surgically created defect was completely closed (×12.5). (B) Defect margin area (×50). (C) The Schneiderian membrane (×50). (D) Middle area (×50).

  • Figure 6 Histologic findings of experimental group 2 (0.5 mg/mL ErhBMP-2) at 8 weeks. (A) The histologic findings were similar to those observed in experimental group 1 (0.05 mg/mL ErhBMP-2) at 8 weeks. More vascularization (arrowheads) and matured lamellar bone (black asterisk) are also evident here (×12.5). (B) Defect margin area both inflammatory cells and blood vessels can be observed, as indicated by the arrow and the arrowhead, respectively. The black asterisk indicates matured lamellar bone (×50). (C) The Schneiderian membrane (×50). (D) Middle area (×50).


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