Long-term delivery enhances in vivo osteogenic efficacy of bone morphogenetic protein-2 compared to short-term delivery |
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Authors: | Jeon Oju Song Su Jin Yang Hee Seok Bhang Suk-Ho Kang Sun-Woong Sung Mi Ae Lee Jong Ho Kim Byung-Soo |
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Affiliation: | a Department of Chemical Engineering, Hanyang University, Seoul 133-791, Republic of Korea b Weldon School of Biomedical Engineering and Department of Pharmaceutics, Purdue University, West Lafayette, IN 47907, USA c Department of Bioengineering, Hanyang University, 17 Haengdang-dong, Seongdong-ku, Seoul 133-791, Republic of Korea d Department of Oral and Maxillofacial Surgery, College of Dentistry, Seoul National University, Seoul 110-744, Republic of Korea |
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Abstract: | In this study, heparin-conjugated poly(l-lactide-co-glycolide) (PLGA) nanospheres (HCPNs) suspended in fibrin gel (group 1) were developed for a long-term delivery of BMP-2, and then used to address the hypothesis that a long-term delivery of BMP-2 would enhance ectopic bone formation compared to a short-term delivery at an equivalent dose. Fibrin gel containing normal PLGA nanospheres (group 2) was used for short-term delivery of BMP-2. The in vitro release of BMP-2 from group 1 was sustained for 4 weeks with no initial burst release. In contrast, 83% of BMP-2 loaded in group 2 was released only for the first 3 days. BMP-2 released from group 1 stimulated an increase in alkaline phosphatase (ALP) activity of osteoblasts for 9 days in vitro. In contrast, BMP-2 released from group 2 induced a transient increase in ALP activity for the first 5 days and a decrease thereafter. Importantly, group 1 induced bone formation to a much greater extent than did group 2, with 2.0-fold greater bone formation area and 3.5-fold greater calcium content, upon implantation into rat hind limb muscle. These results show that long-term delivery of BMP-2 enhances in vivo osteogenic efficacy of the protein compared to short-term delivery at an equivalent dose. |
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Keywords: | Bone morphogenetic protein-2 Bone regeneration Heparin Nanosphere Poly( smallcaps" >l-lactide-co-glycolide) Long-term delivery |
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