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ID 52027
フルテキストURL
著者
Shiozaki, Yasuyuki Okayama Univ, Dept Orthoped Surg
Kitajima, Takashi RIKEN, Nano Med Engn Lab
Mazaki, Tetsuro Okayama Univ, Dept Orthoped Surg
Yoshida, Aki Okayama Univ, Dept Orthoped Surg
Tanaka, Masato Okayama Univ, Dept Orthoped Surg
Umezawa, Akihiro Natl Res Inst Child Hlth & Dev
Nakamura, Mariko Kibi Int Univ, Jr Coll, Dept Hlth & Welf Program
Yoshida, Yasuhiro Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Biomat
Ito, Yoshihiro RIKEN, Nano Med Engn Lab
Ozaki, Toshifumi Okayama Univ, Dept Orthoped Surg
Matsukawa, Akihiro Okayama Univ, Dept Pathol & Expt Med
抄録
Purpose: Bone defects and nonunions are major clinical skeletal problems. Growth factors are commonly used to promote bone regeneration; however, the clinical impact is limited because the factors do not last long at a given site. The introduction of tissue engineering aimed to deter the diffusion of these factors is a promising therapeutic strategy. The purpose of the present study was to evaluate the in vivo osteogenic capability of an engineered bone morphogenetic protein-4 (BMP4) fusion protein. Methods: BMP4 was fused with a nanosized carrier, collagen-binding domain (CBD), derived from fibronectin. The stability of the CBD-BMP4 fusion protein was examined in vitro and in vivo. Osteogenic effects of CBD-BMP4 were evaluated by computer tomography after intramedullary injection without a collagen-sponge scaffold. Recombinant BMP-4, CBD, or vehicle were used as controls. Expressions of bone-related genes and growth factors were compared among the groups. Osteogenesis induced by CBD-BMP4, BMP4, and CBD was also assessed in a bone-defect model. Results: In vitro, CBD-BMP4 was retained in a collagen gel for at least 7 days while BMP4 alone was released within 3 hours. In vivo, CBD-BMP4 remained at the given site for at least 2 weeks, both with or without a collagen-sponge scaffold, while BMP4 disappeared from the site within 3 days after injection. CBD-BMP4 induced better bone formation than BMP4 did alone, CBD alone, and vehicle after the intramedullary injection into the mouse femur. -Bone-related genes and growth factors were expressed at higher levels in CBD-BMP4-treated mice than in all other groups, including BMP4-treated mice. Finally, CBD-BMP4 potentiated more bone formation than did controls, including BMP4 alone, when applied to cranial bone defects without a collagen scaffold. Conclusion: Altogether, nanocarrier-CBD enhanced the retention of BMP4 in the bone, thereby promoting augmented osteogenic responses in the absence of a scaffold. These results suggest that CBD-BMP4 may be clinically useful in facilitating bone formation.
キーワード
BMP4
bone repair
bone tissue engineering
osteogenesis
発行日
2013-04
出版物タイトル
International Journal of Nanomedicine
8巻
1号
開始ページ
1349
終了ページ
1360
ISSN
1178-2013
資料タイプ
学術雑誌論文
オフィシャル URL
http://dx.doi.org/10.2147/IJN.S44124
関連URL
http://ousar.lib.okayama-u.ac.jp/metadata/51957
言語
English
論文のバージョン
publisher
査読
有り
DOI
Web of Sience KeyUT