Chung Yong-Il, Ahn Kang-Min, Jeon Seung-Ho, Lee Seung-Young, Lee Jong-Ho, Tae Giyoong
Research Center for Biomolecular Nanotechnology and Department of Materials Science and Engineering, Gwangju Institute of Science and Technology, 1 Oryong-dong, Buk-gu, Gwangju, 500-712, Republic of Korea.
J Control Release. 2007 Aug 16;121(1-2):91-9. doi: 10.1016/j.jconrel.2007.05.029. Epub 2007 Jun 2.
As an efficient sustained release system of BMP-2, a functional nanoparticle-hydrogel complex, composed of heparin-functionalized nanoparticles and fibrin gel, was developed and used as a bone graft. In vivo bone formation was evaluated by soft X-ray, histology, alkaline phosphatase (ALP) activity, immunostaining, and mineral content analysis, based on the rat calvarial critical size defect model. Significantly improved and effective bone regeneration was achieved with the recombinant BMP-2 (4 mug) loaded nanoparticle-fibrin gel complex, as compared to bare fibrin gel, the nanoparticle-fibrin gel complex without BMP-2, or even the BMP-2 loaded fibrin gel. These improvements included areas such as radiodensity, the bone-specific ALP activity, the osteocalcin immunoreactivity, and the ratios of calcium and phosphate contents with respect to normal bone in the regenerated bone area. The remodeling process of new bone developed with BMP-2 was significantly enhanced, and more mature and highly-mineralized bone was obtained by utilizing the functional nanoparticle-hydrogel complex. These results indicate that the nanoparticle-fibrin gel complex can be a promising candidate for a new bone defect replacement matrix, and an enhanced BMP-2 carrier.
作为一种高效的骨形态发生蛋白-2（BMP-2）缓释系统，一种由肝素功能化纳米颗粒和纤维蛋白凝胶组成的功能性纳米颗粒-水凝胶复合物被研发出来并用作骨移植材料。基于大鼠颅骨临界尺寸缺损模型，通过软X射线、组织学、碱性磷酸酶（ALP）活性、免疫染色和矿物质含量分析对体内骨形成进行评估。与单纯的纤维蛋白凝胶、不含BMP-2的纳米颗粒-纤维蛋白凝胶复合物，甚至是负载BMP-2的纤维蛋白凝胶相比，负载重组BMP-2（4微克）的纳米颗粒-纤维蛋白凝胶复合物实现了显著改善且有效的骨再生。这些改善包括诸如骨密度、骨特异性ALP活性、骨钙素免疫反应性以及再生骨区域中钙和磷含量与正常骨的比率等方面。利用BMP-2形成的新骨的重塑过程显著增强，并且通过使用功能性纳米颗粒-水凝胶复合物获得了更成熟、矿化程度更高的骨。这些结果表明，纳米颗粒-纤维蛋白凝胶复合物有望成为一种新型骨缺损替代基质以及一种增强型BMP-2载体。
