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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
Ozaki, Toshifumi Kaken ID researchmap
Matsukawa, Akihiro ORCID Kaken ID researchmap
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 Science KeyUT