Long-term delivery enhances in vivo osteogenic efficacy of bone morphogenetic protein-2 compared to short-term delivery

被引:163
作者
Jeon, Oju [2 ,3 ,4 ]
Song, Su Jin [2 ]
Yang, Hee Seok [1 ]
Bhang, Suk-Ho [1 ,2 ]
Kang, Sun-Woong [2 ]
Sung, Mi Ae [5 ]
Lee, Jong Ho [5 ]
Kim, Byung-Soo [1 ]
机构
[1] Hanyang Univ, Dept Bioengn, Seoul 133791, South Korea
[2] Hanyang Univ, Dept Chem Engn, Seoul 133791, South Korea
[3] Purdue Univ, Weldon Sch Biomed Engn, W Lafayette, IN 47907 USA
[4] Purdue Univ, Dept Pharmaceut, W Lafayette, IN 47907 USA
[5] Seoul Natl Univ, Coll Dent, Dept Oral & Maxillofacial Surg, Seoul 110744, South Korea
基金
新加坡国家研究基金会;
关键词
bone morphogenetic protein-2; bone regeneration; heparin; nanosphere; poly(L-lactide-co-glycolide); long-term delivery;
D O I
10.1016/j.bbrc.2008.02.099
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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 I 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 I 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 I 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. (C) 2008 Elsevier Inc. All rights reserved.
引用
收藏
页码:774 / 780
页数:7
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