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ID 52027
FullText URL
Author
Shiozaki, Yasuyuki
Kitajima, Takashi
Mazaki, Tetsuro
Yoshida, Aki
Umezawa, Akihiro
Nakamura, Mariko
Yoshida, Yasuhiro
Ito, Yoshihiro
Matsukawa, Akihiro Kakenhi
Abstract
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.
Keywords
BMP4
bone repair
bone tissue engineering
osteogenesis
Published Date
2013-04
Publication Title
International Journal of Nanomedicine
Volume
volume8
Issue
issue1
Start Page
1349
End Page
1360
ISSN
1178-2013
Content Type
Journal Article
Official Url
http://dx.doi.org/10.2147/IJN.S44124
Related Url
http://ousar.lib.okayama-u.ac.jp/metadata/51957
language
英語
File Version
publisher
Refereed
True
DOI
Web of Sience KeyUT