Jeon Oju, Song Su Jin, Yang Hee Seok, Bhang Suk-Ho, Kang Sun-Woong, Sung Mi Ae, Lee Jong Ho, Kim Byung-Soo
Department of Chemical Engineering, Hanyang University, Seoul 133-791, Republic of Korea.
Biochem Biophys Res Commun. 2008 May 2;369(2):774-80. doi: 10.1016/j.bbrc.2008.02.099. Epub 2008 Feb 29.
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.
在本研究中，制备了悬浮于纤维蛋白凝胶中的肝素共轭聚（L-丙交酯-共-乙交酯）（PLGA）纳米球（HCPNs）（第1组），用于长效递送骨形态发生蛋白-2（BMP-2），然后用于验证以下假设：与同等剂量的短期递送相比，BMP-2的长期递送将增强异位骨形成。含有普通PLGA纳米球的纤维蛋白凝胶（第2组）用于BMP-2的短期递送。第1组中BMP-2的体外释放持续4周，无初始突释。相比之下，第2组中负载的BMP-2仅在最初3天释放了83%。第1组释放的BMP-2在体外刺激成骨细胞碱性磷酸酶（ALP）活性增加9天。相比之下，第2组释放的BMP-2在最初5天诱导ALP活性短暂增加，此后降低。重要的是，将其植入大鼠后肢肌肉后，第1组诱导的骨形成程度比第2组大得多，骨形成面积大2.0倍，钙含量高3.5倍。这些结果表明，与同等剂量的短期递送相比，BMP-2的长期递送增强了该蛋白在体内的成骨效力。
