Enhanced in vivo osteogenesis by nanocarrier-fused bone morphogenetic protein-4

Yasuyuki Shiozaki,1,2 Takashi Kitajima,4 Tetsuro Mazaki,1,2 Aki Yoshida,1 Masato Tanaka,1 Akihiro Umezawa,5 Mariko Nakamura,6 Yasuhiro Yoshida,3 Yoshihiro Ito,4 Toshifumi Ozaki,1 Akihiro Matsukawa2 1Department of Orthopedic Surgery, Okayama University, Okayama, Okayama, Japan; 2Department of Patholo...

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Autores principales:	Shiozaki Y, Kitajima T, Mazaki T, Yoshida A, Tanaka M, Umezawa A, Nakamura M, Yoshida Y, Ito Y, Ozaki T, Matsukawa A
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2013
Materias:	Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/91ab5ead9c7449588233ba246c927236
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spelling	oai:doaj.org-article:91ab5ead9c7449588233ba246c9272362021-12-02T01:58:51ZEnhanced in vivo osteogenesis by nanocarrier-fused bone morphogenetic protein-41176-91141178-2013https://doaj.org/article/91ab5ead9c7449588233ba246c9272362013-04-01T00:00:00Zhttp://www.dovepress.com/enhanced-in-vivo-osteogenesis-by-nanocarrier-fused-bone-morphogenetic--a12703https://doaj.org/toc/1176-9114https://doaj.org/toc/1178-2013Yasuyuki Shiozaki,1,2 Takashi Kitajima,4 Tetsuro Mazaki,1,2 Aki Yoshida,1 Masato Tanaka,1 Akihiro Umezawa,5 Mariko Nakamura,6 Yasuhiro Yoshida,3 Yoshihiro Ito,4 Toshifumi Ozaki,1 Akihiro Matsukawa2 1Department of Orthopedic Surgery, Okayama University, Okayama, Okayama, Japan; 2Department of Pathology and Experimental Medicine, Okayama University, Okayama, Okayama, Japan; 3Department of Biomaterials, Graduate School of Medical, Dentistry, and Pharmaceutical Sciences, Okayama University, Okayama, Okayama, Japan; 4Nano Medical Engineering Laboratory, RIKEN, Wako, Saitama, Japan; 5National Research Institute for Child Health and Development, Okura, Tokyo, Japan; 6Department of Health and Welfare Program, Kibi International University Junior College, Takahashi, Okayama, Japan 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, osteogenesisShiozaki YKitajima TMazaki TYoshida ATanaka MUmezawa ANakamura MYoshida YIto YOzaki TMatsukawa ADove Medical PressarticleMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol 2013, Iss default, Pp 1349-1360 (2013)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine (General) R5-920
spellingShingle	Medicine (General) R5-920 Shiozaki Y Kitajima T Mazaki T Yoshida A Tanaka M Umezawa A Nakamura M Yoshida Y Ito Y Ozaki T Matsukawa A Enhanced in vivo osteogenesis by nanocarrier-fused bone morphogenetic protein-4
description	Yasuyuki Shiozaki,1,2 Takashi Kitajima,4 Tetsuro Mazaki,1,2 Aki Yoshida,1 Masato Tanaka,1 Akihiro Umezawa,5 Mariko Nakamura,6 Yasuhiro Yoshida,3 Yoshihiro Ito,4 Toshifumi Ozaki,1 Akihiro Matsukawa2 1Department of Orthopedic Surgery, Okayama University, Okayama, Okayama, Japan; 2Department of Pathology and Experimental Medicine, Okayama University, Okayama, Okayama, Japan; 3Department of Biomaterials, Graduate School of Medical, Dentistry, and Pharmaceutical Sciences, Okayama University, Okayama, Okayama, Japan; 4Nano Medical Engineering Laboratory, RIKEN, Wako, Saitama, Japan; 5National Research Institute for Child Health and Development, Okura, Tokyo, Japan; 6Department of Health and Welfare Program, Kibi International University Junior College, Takahashi, Okayama, Japan 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
format	article
author	Shiozaki Y Kitajima T Mazaki T Yoshida A Tanaka M Umezawa A Nakamura M Yoshida Y Ito Y Ozaki T Matsukawa A
author_facet	Shiozaki Y Kitajima T Mazaki T Yoshida A Tanaka M Umezawa A Nakamura M Yoshida Y Ito Y Ozaki T Matsukawa A
author_sort	Shiozaki Y
title	Enhanced in vivo osteogenesis by nanocarrier-fused bone morphogenetic protein-4
title_short	Enhanced in vivo osteogenesis by nanocarrier-fused bone morphogenetic protein-4
title_full	Enhanced in vivo osteogenesis by nanocarrier-fused bone morphogenetic protein-4
title_fullStr	Enhanced in vivo osteogenesis by nanocarrier-fused bone morphogenetic protein-4
title_full_unstemmed	Enhanced in vivo osteogenesis by nanocarrier-fused bone morphogenetic protein-4
title_sort	enhanced in vivo osteogenesis by nanocarrier-fused bone morphogenetic protein-4
publisher	Dove Medical Press
publishDate	2013
url	https://doaj.org/article/91ab5ead9c7449588233ba246c927236
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_version_	1718402790022184960

Enhanced in vivo osteogenesis by nanocarrier-fused bone morphogenetic protein-4

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