Bone regeneration by low-dose recombinant human bone morphogenetic protein-2 carried on octacalcium phosphate collagen composite

Nguyen Dien Bien, Kei Ichiro Miura, Yoshinori Sumita, Yuya Nakatani, Rena Shido, Fumihiko Kajii, Shinji Kamakura, Izumi Asahina

Research output: Contribution to journalArticlepeer-review

5 Citations (Scopus)


Bone morphogenetic protein-2 (BMP-2) has diverse functions and is especially important in bone and cartilage development. Recombinant human BMP-2 (rhBMP-2) is an osteoinductive growth factor that has been clinically applied as a bone graft substitute. However, high-dose rhBMP-2 can cause complications such as induction of significant swelling that can endanger the patient’s life. Atelocollagen sponge (ACS) is the commercially provided standard carrier of rhBMP-2 in clinical applications. However, a large concentration of rhBMP-2 is required to be clinically effective with ACS as the carrier. Octacalcium phosphate/collagen (OCP/Col) has been shown to be an excellent bone substitute compared with other bone substitute materials such as hydroxyapatite or β-tricalcium phosphate due to its biological properties. In this study, we evaluated the use of OCP/Col as a carrier to minimize the effective dose of rhBMP-2. ACS or OCP/Col discs impregnated with different rhBMP-2 concentrations were implanted in mice calvarial bone defects. Morphological analysis with micro-CT both at 4 and 6 weeks post-implantation showed homogenous hard tissue formation in the defects of the OCP/Col group at all rhBMP-2 concentrations tested (0, 0.25, 0.50, or 1.00 μg). In contrast, ACS alone or with 0.25 μg of rhBMP-2 showed almost no bone formation. However, bone mineral density in all groups of ACS and OCP/Col was not dependent on rhBMP-2 concentration. Histological evaluation indicated that bone formation progressed depending on rhBMP-2 concentration in the defects of both the ACS and OCP/Col groups, although the newly formed bone area was significantly higher in the OCP/Col group than in the ACS group. These results indicate that OCP/Col could be an effective carrier of rhBMP-2, minimizing the application dose of rhBMP-2 in clinical settings and avoiding the complications caused by high-dose rhBMP-2.

Original languageEnglish
Pages (from-to)123-130
Number of pages8
JournalJournal of Hard Tissue Biology
Issue number2
Publication statusPublished - 2020


  • Bone morphogenetic protein-2
  • Bone regeneration
  • Carrier
  • Collagen
  • Octacalcium phosphate

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Biochemistry
  • Biomaterials
  • Orthopedics and Sports Medicine
  • Dentistry(all)
  • Cell Biology


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