Improving Bone Formation in a Rat Femur Segmental Defect by Controlling Bone Morphogenetic Protein-2 Release
Improving Bone Formation in a Rat Femur Segmental Defect by Controlling Bone Morphogenetic Protein-2 Release
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DOI：
10.1089/ten.tea.2010.0446
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发表时间：
2011-07-01
影响因子：
4.1
通讯作者：
Wenke, Joseph C.
中科院分区：
文献类型：
--
作者：
Brown, Kate V.;Li, Bing;Wenke, Joseph C.
骨不连是开放性骨折和其他严重骨损伤的常见并发症。重组人骨形态发生蛋白-2 （rhBMP-2）在胶原蛋白海绵上的传递促进骨折愈合。然而，rhBMP-2的爆发性释放需要超生理剂量的rhBMP-2来实现强大的成骨效果，这引入了异位骨形成和严重炎症的风险，并增加了成本。虽然rhBMP-2的理想药代动力学包括爆发和持续释放的概念被普遍接受，但对释放动力学对新骨形成的影响的研究有限。在本研究中，在一个临界尺寸的大鼠节段缺损模型中，比较了具有不同rhBMP-2释放动力学的可生物降解聚氨酯（PUR）和PUR/微球[PUR/聚（乳酸-羟基乙酸）)]复合支架与胶原海绵递送系统。微计算机断层扫描分析表明，与加载rhBMP-2的胶原海绵相比，断裂后持续释放rhBMP-2的PUR支架再生的新骨多50%，而不断裂的持续释放并不比没有rhBMP-2的支架形成更多的骨。这项研究表明，使用PUR支架可以实现rhBMP-2的假定最佳释放特征（即，爆裂后持续释放），并且这种增强的药代动力学比临床可用的大鼠股骨临界尺寸缺陷的护理标准再生更多的骨。
Nonunion is a common complication in open fractures and other severe bone injuries. Recombinant human bone morphogenetic protein-2 (rhBMP-2) delivered on a collagen sponge enhances healing of fractures. However, the burst release of rhBMP-2 necessitates supra-physiological doses of rhBMP-2 to achieve a robust osteogenic effect, which introduces risk of ectopic bone formation and severe inflammation and increases the cost. Although the concept that the ideal pharmacokinetics for rhBMP-2 includes both a burst and sustained release is generally accepted, investigations into the effects of the release kinetics on new bone formation are limited. In the present study, biodegradable polyurethane (PUR) and PUR/microsphere [PUR/poly(lactic-co-glycolic acid)] composite scaffolds with varying rhBMP-2 release kinetics were compared to the collagen sponge delivery system in a critical-sized rat segmental defect model. Microcomputed tomography analysis indicated that a burst followed by a sustained release of rhBMP-2 from the PUR scaffolds regenerated 50% more new bone than the collagen sponge loaded with rhBMP-2, whereas a sustained release without the burst did not form significantly more bone than the scaffold without rhBMP-2. This study demonstrated that the putative optimal release profile (i.e., burst followed by sustained release) for rhBMP-2 can be achieved using PUR scaffolds, and that this enhanced pharmacokinetics regenerated more bone than the clinically available standard of care in a critical-sized defect in rat femora.