Center for Musculoskeletal Surgery, Charité - Universitätsmedizin Berlin, Germany.
BMC Musculoskelet Disord. 2011 Jul 15;12:163. doi: 10.1186/1471-2474-12-163.
BMP-2 is known to accelerate fracture healing and might also enhance osseointegration and implant fixation. Application of recombinant BMP-2 has a time-limited effect. Therefore, a gene transfer approach with a steady production of BMP-2 appears to be attractive. The aim of this study was to examine the effect of locally applied BMP-2 plasmids on the bone-implant integration in a non-weight bearing rabbit tibia model using a comparatively new non-viral copolymer-protected gene vector (COPROG).
Sixty rabbits were divided into 4 groups. All of them received nailing of both tibiae. The verum group had the nails inserted with the COPROG vector and BMP-2 plasmids using fibrin glue as a carrier. Controls were a group with fibrin glue only and a blank group. After 28 and 56 days, these three groups were sacrificed and one tibia was randomly chosen for biomechanical testing, while the other tibia underwent histomorphometrical examination. In a fourth group, a reporter-gene was incorporated in the fibrin glue instead of the BMP-2 formula to prove that transfection was successful.
Implant fixation strength was significantly lower after 28 and 56 days in the verum group. Histomorphometry supported the findings after 28 days, showing less bone-implant contact.In the fourth group, successful transfection could be confirmed by detection of the reporter-gene in 20 of 22 tibiae. But, also systemic reporter-gene expression was found in heterotopic locations, showing an undesired spreading of the locally applied gene formula.
Our results underline the transfecting capability of this vector and support the idea that BMP-2 might diminish osseointegration. Further studies are necessary to specify the exact mechanisms and the systemic effects.
BMP-2 已知可加速骨折愈合，并且还可能增强骨整合和植入物固定。应用重组 BMP-2 的效果具有时间限制。因此，具有稳定 BMP-2 产生的基因转移方法似乎很有吸引力。本研究的目的是使用一种新型的非病毒共聚物保护基因载体（COPROG），在非承重兔胫骨模型中研究局部应用 BMP-2 质粒对骨-植入物整合的影响。
60 只兔子被分为 4 组。所有兔子的胫骨均接受了钉固定。真组将 COPROG 载体和 BMP-2 质粒插入带有纤维蛋白胶作为载体的钉子中。对照组仅为纤维蛋白胶组，空白组为空白组。28 天和 56 天后，这些组中的 3 组被处死，随机选择一只胫骨进行生物力学测试，另一只胫骨进行组织形态计量学检查。在第 4 组中，纤维蛋白胶中加入报告基因代替 BMP-2 公式，以证明转染成功。
28 天和 56 天后，真组的植入物固定强度明显降低。28 天后的组织形态计量学支持了这些发现，显示出较少的骨-植入物接触。在第 4 组中，通过检测 22 只胫骨中的 20 只，成功确认了报告基因的转染。但是，还在异位位置发现了系统报告基因表达，表明局部应用基因公式的扩散不理想。
我们的结果强调了该载体的转染能力，并支持 BMP-2 可能减少骨整合的观点。进一步的研究是必要的，以明确确切的机制和系统效应。
