start-ver=1.4
cd-journal=joma
no-vol=8
cd-vols=
no-issue=1
article-no=
start-page=1349
end-page=1360
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2013
dt-pub=201304
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Enhanced in vivo osteogenesis by nanocarrier-fused bone morphogenetic protein-4
en-subtitle=
kn-subtitle=
en-abstract=
kn-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.
en-copyright=
kn-copyright=

en-aut-name=ShiozakiYasuyuki
en-aut-sei=Shiozaki
en-aut-mei=Yasuyuki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=

en-aut-name=KitajimaTakashi
en-aut-sei=Kitajima
en-aut-mei=Takashi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=

en-aut-name=MazakiTetsuro
en-aut-sei=Mazaki
en-aut-mei=Tetsuro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=

en-aut-name=YoshidaAki
en-aut-sei=Yoshida
en-aut-mei=Aki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=

en-aut-name=TanakaMasato
en-aut-sei=Tanaka
en-aut-mei=Masato
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=

en-aut-name=UmezawaAkihiro
en-aut-sei=Umezawa
en-aut-mei=Akihiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
ORCID=

en-aut-name=NakamuraMariko
en-aut-sei=Nakamura
en-aut-mei=Mariko
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=7
ORCID=

en-aut-name=YoshidaYasuhiro
en-aut-sei=Yoshida
en-aut-mei=Yasuhiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=8
ORCID=

en-aut-name=ItoYoshihiro
en-aut-sei=Ito
en-aut-mei=Yoshihiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=9
ORCID=

en-aut-name=OzakiToshifumi
en-aut-sei=Ozaki
en-aut-mei=Toshifumi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=10
ORCID=

en-aut-name=MatsukawaAkihiro
en-aut-sei=Matsukawa
en-aut-mei=Akihiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=11
ORCID=

affil-num=1
en-affil=
kn-affil=Okayama Univ, Dept Orthoped Surg

affil-num=2
en-affil=
kn-affil=RIKEN, Nano Med Engn Lab

affil-num=3
en-affil=
kn-affil=Okayama Univ, Dept Orthoped Surg

affil-num=4
en-affil=
kn-affil=Okayama Univ, Dept Orthoped Surg

affil-num=5
en-affil=
kn-affil=Okayama Univ, Dept Orthoped Surg

affil-num=6
en-affil=
kn-affil=Natl Res Inst Child Hlth & Dev

affil-num=7
en-affil=
kn-affil=Kibi Int Univ, Jr Coll, Dept Hlth & Welf Program

affil-num=8
en-affil=
kn-affil=Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Biomat

affil-num=9
en-affil=
kn-affil=RIKEN, Nano Med Engn Lab

affil-num=10
en-affil=
kn-affil=Okayama Univ, Dept Orthoped Surg

affil-num=11
en-affil=
kn-affil=Okayama Univ, Dept Pathol & Expt Med
en-keyword=BMP4
kn-keyword=BMP4
en-keyword=bone repair
kn-keyword=bone repair
en-keyword=bone tissue engineering
kn-keyword=bone tissue engineering
en-keyword=osteogenesis
kn-keyword=osteogenesis
END