The kinetic and biological activity of different loaded rhBMP-2 calcium phosphate cement implants in rats
The kinetic and biological activity of different loaded rhBMP-2 calcium phosphate cement implants in rats
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DOI：
10.1002/jbm.a.31830
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发表时间：
2008-12-01
影响因子：
4.9
通讯作者：
Jansen, John A.
中科院分区：
文献类型：
--
作者：
Bodde, Esther W. H.;Boerman, Otto C.;Jansen, John A.
由于生长因子的加入，成骨骨移植替代物可以改善大面积骨缺损的愈合。当与突释相比时，这些生长因子的持续释放提供更有效的生物活性，并且可能减少骨再生所需的剂量，这是出于社会经济和安全原因所期望的。在这项研究中，我们比较了不同的rhBMP-2负载在持续释放系统的钙磷水泥和PLGA微粒，并能够耦合动力学的生物活性数据。52只大鼠接受了一个临界尺寸的颅骨缺损，该缺损保持开放或用骨水泥复合材料填充。植入物由普通、高和低五倍剂量rhBMP-2组组成。植入时间为4周和12周。通过131 I标记的rhBMP-2的荧光成像监测纵向体内释放。免疫组织化学图像的定量分析显示两种剂量的I-131-rhBMP-2持续释放，两种负载之间具有不同的释放曲线。然而，两种植入物制剂中保留了约70%的初始剂量。尽管释放了少量rhBMP-2（5周内2.4 +/- 0.8 μ g），但组织学显示高剂量植入物中存在缺损桥接。低剂量植入物的释放不足以增强骨形成。所有制剂中的植入物降解均有限，但主要见于高剂量组。低量的持续释放rhBMP-2足以桥接临界尺寸的缺损。由于缓慢的释放速率和有限的降解，大量的rhBMP-2保留在植入物中。(C)2008 Wiley Periodicals，Inc. J Biomed Mater Res 87A：780-791，2008
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 I-131-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 mu g 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. (C) 2008 Wiley Periodicals, Inc. J Biomed Mater Res 87A: 780-791, 2008