Bodde Esther W H, Boerman Otto C, Russel Frans G M, Mikos Antonios G, Spauwen Paul H M, Jansen John A
Department of Periodontology and Biomaterials, Radboud University Nijmegen Medical Center, Nijmegen, The Netherlands.
J Biomed Mater Res A. 2008 Dec 1;87(3):780-91. doi: 10.1002/jbm.a.31830.
The healing of large bone defects can be improved by osteogenic bone graft substitutes, due to growth factor inclusion. A sustained release of these growth factors provides more efficient bioactivity when compared with burst release and might reduce the dose required for bone regeneration, which is desirable for socioeconomical and safety reasons. In this study, we compared different rhBMP-2 loadings in a sustained release system of CaP cement and PLGA-microparticles and were able to couple kinetic to biological activity data. Fifty-two rats received a critical-size cranial defect, which was left open or filled with the cement composites. The implants consisted of plain, high, and five-fold lower dose rhBMP-2 groups. Implantation time was 4 and 12 weeks. Longitudinal in vivo release was monitored by scintigraphic imaging of (131)I-labeled rhBMP-2. Quantitative analysis of the scintigraphic images revealed a sustained release of (131)I-rhBMP-2 for both doses, with different release profiles between the two loadings. However, around 70% of the initial dose was retained in both implant formulations. Although low amounts of rhBMP-2 were released (2.4 +/- 0.8 mug in 5 weeks), histology showed defect bridging in the high-dose implants. Release out of the low-dose implants was not sufficient to enhance bone formation. Implant degradation was limited in all formulations, but was mainly seen in the high-dose group. Low amounts of sustained released rhBMP-2 were sufficient to bridge critically sized defects. A substantial amount of rhBMP-2 was retained in the implants because of the slow release rate and the limited degradation.
由于包含生长因子，成骨骨移植替代物可促进大骨缺损的愈合。与突发释放相比，这些生长因子的持续释放具有更高的生物活性，并且可能减少骨再生所需的剂量，出于社会经济和安全原因，这是可取的。在本研究中，我们比较了CaP骨水泥和PLGA微粒缓释系统中不同的rhBMP-2负载量，并能够将动力学与生物活性数据联系起来。52只大鼠接受了临界尺寸的颅骨缺损，缺损处保持开放或填充骨水泥复合材料。植入物包括普通剂量、高剂量和低五倍剂量的rhBMP-2组。植入时间为4周和12周。通过对(131)I标记的rhBMP-2进行闪烁成像监测体内纵向释放。闪烁图像的定量分析显示，两种剂量的(131)I-rhBMP-2均为持续释放，两种负载量之间的释放曲线不同。然而，两种植入物配方中约70%的初始剂量被保留。尽管释放的rhBMP-2量较低(5周内为2.4±0.8微克)，但组织学显示高剂量植入物中有缺损桥接。低剂量植入物的释放不足以促进骨形成。所有配方中植入物的降解都有限，但主要出现在高剂量组。低量的持续释放rhBMP-2足以桥接临界尺寸的缺损。由于释放速率缓慢和降解有限，大量rhBMP-2保留在植入物中。
