Chen Bing, Lin Hang, Wang Jianhua, Zhao Yannan, Wang Bin, Zhao Wenxue, Sun Wenjie, Dai Jianwu
Key Laboratory of Molecular and Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, 3 Nanyitiao, Zhongguancun, Beijing 100080, China.
Biomaterials. 2007 Feb;28(6):1027-35. doi: 10.1016/j.biomaterials.2006.10.013. Epub 2006 Nov 13.
Considerable research has been focused on the development of bone morphogenetic protein-2 (BMP-2) delivery system for homologous and efficient bone regeneration. The aim of the present study was to develop a collagen-based targeting bone repair system. A collagen-binding domain (CBD) was added to the N-terminal of native BMP-2 to allow it bind to collagen specifically. We showed that the collagen-binding bone morphogenetic protein-2 (named bone morphogenetic protein2-h, BMP2-h) had maintained the full biological activity as compared to rhBMP2 lacking the CBD. In vitro functional study also demonstrated that collagen matrix could maintain higher bioactivity of BMP2-h than native BMP-2. When demineralized bone matrix (DBM) impregnated with BMP2-h was implanted subcutaneously in rats, homogeneous bone formation was observed. Moreover, in a rabbit mandible defect model, surgical implantation of collagen matrix loaded with BMP2-h exhibited remarkable osteoinductive properties and excellent homogeneous bone formation. Our studies suggested that this novel collagen-based BMP-2 targeting bone repair system induced better bone formation not only in quantity but also in quality. Similar approaches may also be used for the repair of other tissue injuries.
大量研究聚焦于开发用于同源和高效骨再生的骨形态发生蛋白-2（BMP-2）递送系统。本研究的目的是开发一种基于胶原蛋白的靶向骨修复系统。在天然BMP-2的N端添加了一个胶原蛋白结合结构域（CBD），使其能够特异性结合胶原蛋白。我们发现，与缺乏CBD的重组人骨形态发生蛋白2（rhBMP2）相比，胶原蛋白结合骨形态发生蛋白-2（命名为骨形态发生蛋白2-h，BMP2-h）保持了完整的生物活性。体外功能研究还表明，胶原基质能比天然BMP-2更好地维持BMP2-h的生物活性。当将负载有BMP2-h的脱矿骨基质（DBM）皮下植入大鼠体内时，观察到了均匀的骨形成。此外，在兔下颌骨缺损模型中，手术植入负载有BMP2-h的胶原基质表现出显著的骨诱导特性和出色的均匀骨形成。我们的研究表明，这种新型的基于胶原蛋白的BMP-2靶向骨修复系统不仅在数量上而且在质量上都能诱导更好的骨形成。类似的方法也可用于修复其他组织损伤。
