Seoul National University, Seoul, Republic of Korea.
Artif Organs. 2010 Dec;34(12):1150-3. doi: 10.1111/j.1525-1594.2009.00988.x.
Bone morphogenetic protein-2 (BMP-2) induces bone regeneration in a dose-dependent manner, with higher doses of BMP-2 inducing greater bone formation. Previously, we showed that long-term delivery of BMP-2 provides better ectopic bone formation than short-term delivery of an equivalent dose. In the present study, we investigated the efficacy of orthotopic bone formation over a range of BMP-2 doses, using different delivery modes. Heparin-conjugated poly(lactic-co-glycolic acid) nanospheres suspended in fibrin gel were used as a long-term delivery system, and fibrin gel was used as a short-term delivery system. Different doses of BMP-2 were delivered to mouse calvarial defects using either long-term or short-term delivery systems. Eight weeks after treatment, bone regeneration was evaluated by histomorphometry. For both delivery systems, bone regeneration increased as the BMP-2 dose increased up to 1 µg and did not increase beyond this dose. Importantly, at BMP-2 doses higher than 1 µg, long-term delivery resulted in much greater bone formation than short-term delivery. This study shows that long-term delivery of BMP-2 is more effective at enhancing orthotopic bone formation than short-term delivery over a range of doses.
骨形态发生蛋白 2（BMP-2）以剂量依赖性方式诱导骨再生，较高剂量的 BMP-2 诱导更大的骨形成。先前，我们表明，BMP-2 的长期递送比等量剂量的短期递送提供更好的异位骨形成。在本研究中，我们使用不同的递送方式研究了一系列 BMP-2 剂量的原位骨形成的功效。肝素结合的聚（乳酸-共-乙醇酸）纳米球悬浮在纤维蛋白凝胶中用作长期递送系统，纤维蛋白凝胶用作短期递送系统。使用长期或短期递送系统将不同剂量的 BMP-2 递送到小鼠颅骨缺损中。治疗 8 周后，通过组织形态计量学评估骨再生。对于两种递送系统，骨再生随着 BMP-2 剂量的增加而增加，直到 1μg 为止，并且不会超过该剂量增加。重要的是，在 BMP-2 剂量高于 1μg 时，长期递送比短期递送导致更大的骨形成。这项研究表明，在一系列剂量下，与短期递送相比，BMP-2 的长期递送更有效地增强了原位骨形成。
