Escherichia coli-derived BMP-2-absorbed β-TCP granules induce bone regeneration in rabbit critical-sized femoral segmental defects

  • Yu Kuroiwa
  • Takahiro NiikuraEmail author
  • Sang Yang Lee
  • Keisuke Oe
  • Takashi Iwakura
  • Tomoaki Fukui
  • Tomoyuki Matsumoto
  • Takehiko Matsushita
  • Kotaro Nishida
  • Ryosuke Kuroda
Original Paper



This study investigated whether Escherichia coli-derived bone morphogenetic protein (BMP)-2 (E-BMP-2) adsorbed onto β-tricalcium phosphate (β-TCP) granules can induce bone regeneration in critical-size femoral segmental defects in rabbits.


Bone defects 20 mm in size and stabilized with an external fixator were created in the femur of New Zealand white rabbits, which were divided into BMP-2 and control groups. E-BMP-2-loaded β-TCP granules were implanted into defects of the BMP-2 group, whereas defects in the controls were implanted with β-TCP granules alone. At 12 and 24 weeks after surgery, radiographs were obtained of the femurs and histological and biomechanical assessments of the defect area were performed. Bone regeneration was quantified using micro-computed tomography at 24 weeks.


Radiographic and histologic analyses revealed bone regeneration in the BMP-2 group but not the control group; no fracturing of newly formed bone occurred when the external fixator was removed at 12 weeks. At 24 weeks, tissue mineral density, the ratio of bone volume to total volume, and volumetric bone mineral density of the callus were higher in the BMP-2 group than in control animals. In the former, ultimate stress, extrinsic stiffness, and failure energy measurements for the femurs were higher at 24 weeks than at 12 weeks.


E-BMP-2-loaded β-TCP granules can effectively promote bone regeneration in long bone defects.


Bone morphogenetic protein-2 β-Tricalcium phosphate Bone defect Bone regeneration 



The authors thank Mr. T. Ueha, Ms. M. Yasuda, Ms. K. Tanaka, Ms. M. Nagata (Department of Orthopaedic Surgery, Kobe University Graduate School of Medicine), and Mr. H. Irie (Osteopharma) for excellent technical assistance.


This study was supported by a grant from the Hyogo Science and Technology Association.

Compliance with ethical standards

Conflict of interest

β-TCP granules were provided free of charge by HOYA Technosurgical Corporation (Mashiko, Japan). E-BMP-2 was provided free of charge by Osteopharma.

Ethical approval

Procedures involving animals were performed with approval and under the guidance of the Animal Care and Use Committee of Kobe University Graduate School of Medicine.


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Copyright information

© SICOT aisbl 2018

Authors and Affiliations

  • Yu Kuroiwa
    • 1
  • Takahiro Niikura
    • 1
    Email author
  • Sang Yang Lee
    • 1
  • Keisuke Oe
    • 1
  • Takashi Iwakura
    • 1
  • Tomoaki Fukui
    • 1
  • Tomoyuki Matsumoto
    • 1
  • Takehiko Matsushita
    • 1
  • Kotaro Nishida
    • 1
  • Ryosuke Kuroda
    • 1
  1. 1.Department of Orthopaedic SurgeryKobe University Graduate School of MedicineKobeJapan

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