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Bone morphogenetic protein-2 in biodegradable gelatin and β-tricalcium phosphate sponges enhances the in vivo bone-forming capability of bone marrow mesenchymal stem cells

Authors

  • Mika Tadokoro,

    1. Health Research Institute, National Institute of Advanced Industrial Science and Technology (AIST), 3-11-46 Nakoji, Amagasaki, Hyogo 661-0974, Japan
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  • Asako Matsushima,

    1. Health Research Institute, National Institute of Advanced Industrial Science and Technology (AIST), 3-11-46 Nakoji, Amagasaki, Hyogo 661-0974, Japan
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  • Noriko Kotobuki,

    1. Health Research Institute, National Institute of Advanced Industrial Science and Technology (AIST), 3-11-46 Nakoji, Amagasaki, Hyogo 661-0974, Japan
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  • Motohiro Hirose,

    1. Human Technology Research Institute, National Institute of Advanced Industrial Science and Technology (AIST), 1-1-1 Higashi, Tsukuba, Ibaraki 305-8566, Japan
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  • Yu Kimura,

    1. Department of Biomaterials, Field of Tissue Engineering, Institute for Frontier Medical Sciences, Kyoto University, 53 Kawara-cho Shogoin, Sakyo-ku, Kyoto 606-8507, Japan
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  • Yasuhiko Tabata,

    1. Department of Biomaterials, Field of Tissue Engineering, Institute for Frontier Medical Sciences, Kyoto University, 53 Kawara-cho Shogoin, Sakyo-ku, Kyoto 606-8507, Japan
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  • Koji Hattori,

    1. Health Research Institute, National Institute of Advanced Industrial Science and Technology (AIST), 3-11-46 Nakoji, Amagasaki, Hyogo 661-0974, Japan
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  • Hajime Ohgushi

    Corresponding author
    1. Health Research Institute, National Institute of Advanced Industrial Science and Technology (AIST), 3-11-46 Nakoji, Amagasaki, Hyogo 661-0974, Japan
    • Health Research Institute, National Institute of Advanced Industrial Science and Technology (AIST), 3-11-46 Nakoji, Amagasaki, Hyogo 661-0974, Japan.
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Abstract

Bone marrow mesenchymal stem cells (MSCs) have been used for bone tissue engineering due to their osteogenic differentiation capability, but their application is controversial. To enhance their capability, we prepared biodegradable gelatin sponges incorporating β-tricalcium phosphate ceramics (GT sponge), which has been shown to possess excellent controlled drug-release properties. The GT sponge was used as a carrier for both rat MSCs and bone morphogenetic protein-2 (BMP-2) and osteogenic differentiation was assessed by subcutaneous implantation of four different kinds of implants, i.e. GT-alone, MSC–GT composites, BMP–GT composites and BMP–GT composites supplemented with MSCs (BMP–MSC–GT) in rats. Two weeks after implantation, histological sections showed new bone formation in the peripheral parts of the BMP–GT and in almost the total volume of the BMP–MSC–GT implants. After 4 weeks, histology as well as microCT analyses demonstrated extensive bone formation in BMP–MSC–GT implants. Gene expression and biochemical analyses of both alkaline phosphatase and bone-specific osteocalcin confirmed the histological findings. These results indicate that the combination of MSCs, GT and BMP synergistically enhances osteogenic capability and provides a rational basis for their clinical application in bone reconstruction. Copyright © 2011 John Wiley & Sons, Ltd.

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