Characterization of absorbable collagen sponges as rhBMP-2 carriers
Characterization of absorbable collagen sponges as rhBMP-2 carriers
复制标题
DOI：
10.1016/s0378-5173(99)00174-x
复制
发表时间：
1999-09-30
影响因子：
5.8
通讯作者：
Sargeant, C
中科院分区：
文献类型：
--
作者：
Friess, W;Uludag, H;Sargeant, C
在临床应用中，将重组人骨形态发生蛋白（rhBMP-2）浸泡在可吸收胶原海绵（ACS）上进行骨再生。因此，植入期间机械处理时rhBMP-2的损失以及载体对体内保留的潜在影响令人感兴趣。从应用模式来看药物和载体之间的相互作用，并研究了可以从组合物机械表达的蛋白质的量。结果表明，rhBMP-2与胶原系统结合。最亲水的双延伸同源二聚体显示出最小的ACS结合亲和力。通过延长浸泡和植入之间的等待时间，可以增加蛋白质掺入。此外，可以表达的rhBMP-2的量被较重的ACS材料减少，并且允许较短的等待期，特别是在较低的rhBMP-2浓度下。ACS与甲醛的交联导致rhBMP-2与胶原的结合减少，通过直接阻碍结合或减少肿胀和可用结合位点的数量。较高的产品pH值或阴离子浓度能够增加rhBMP-2的掺入，但受到rhBMP-2潜在沉淀的限制。尽管环氧乙烷灭菌后ACS发生了各种化学变化，但掺入量没有显着变化。使用大鼠异位植入模型研究I-125-rhBMP-2从胶原海绵中的体内释放动力学。所测试的ACS/rhBMP-2系统在rhBMP-2的体内保留方面表现出较小但显著的差异。因此，重要的是pH值、阴离子浓度、交联和ACS质量的变异性尽可能小，以实现一致或最大结合，并避免rhBMP-2沉淀。此外，这些特性对于其他体内应用可能是重要的。(C)1999 Elsevier Science B. V.保留所有权利。
For clinical use recombinant human bone morphogenetic protein (rhBMP-2) is soaked onto an absorbable collagen sponge (ACS) for bone regeneration. Therefore, loss of rhBMP-2 upon mechanical handling during implantation and a potential effect of the carrier on in vivo retention is of interest. The interactions between drug and carrier were looked at from the application mode and the amount of protein which can be mechanically expressed from the combination was investigated. The results indicated that rhBMP-2 binds to the collagen system. The most hydrophilic double extended homodimer showed the least binding affinity to ACS. By extending the waiting time between soaking and implantation, protein incorporation could be increased. In addition, the amount of rhBMP-2 which could be expressed was reduced by heavier ACS material and allowed for a shorter waiting period, especially at lower rhBMP-2 concentration. Crosslinking of ACS with formaldehyde led to reduced binding of rhBMP-2 to collagen either by direct hindrance of binding or reduction in swelling and number of binding sites available. Higher product pH or anion concentration enabled to increase rhBMP-2 incorporation but was limited by the potential precipitation of rhBMP-2. Despite a variety of chemical changes of ACS by ethylene oxide sterilization incorporation was not changed significantly. The in vivo release kinetics of I-125-rhBMP-2 from the collagen sponge were studied using a rat ectopic implant model. The ACS/rhBMP-2 systems tested demonstrated small, but significant differences in the in vivo retention of rhBMP-2. Consequently, it is important to have as little variability in pH, anion concentration, crosslinking and ACS mass as possible to achieve consistent or maximum binding and to avoid rhBMP-2 precipitation. Furthermore, these characteristics can be important for other in vivo applications. (C) 1999 Elsevier Science B.V. All rights reserved.