Effect of varied release kinetics of the osteogenic thrombin peptide TP508 from biodegradable, polymeric scaffolds on bone formation in vivo

Effect of varied release kinetics of the osteogenic thrombin peptide TP508 from biodegradable, polymeric scaffolds on bone formation in vivo
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DOI:
10.1002/jbm.a.30265
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发表时间:
2005-03-15
影响因子:
4.9
通讯作者:
Jansen, JA
Jansen, JA
中科院分区:
工程技术3区
文献类型:
--
作者:
Hedberg, EL;Kroese-Deutman, HC;Jansen, JA

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本研究旨在评价骨传导聚富马酸丙二酯(PPF)复合支架中成骨凝血酶多肽TP508的不同释放动力学对体内骨形成的影响。以不同的TP508剂量(200、100、0µg)和释放动力学(大释放、最小释放或不释放)构建四类支架,植入兔桡骨15.0 mm节段性缺损处。术后12周处死动物,通过光镜、组织学记分分析和组织形态计量学分析对种植体进行分析。所有类别的样本都显示在靠近缺损处边缘的支架毛孔内有骨生长。在没有观察到骨骼的区域,毛孔主要由纤维组织填充,所有级别的炎症反应都很轻微。与其他类型的支架相比,总剂量为200µg TP508的支架具有较大的爆裂释放曲线,这些支架沿支架表面引导的骨形成在统计学上更多,这些支架平均80%的缺损处与骨桥接,而其他支架类的桥接长度为10%或更少。这些结果表明,体内骨形成对PPF复合支架控释的反应程度取决于所掺入的成骨多肽的释放动力学。(C)2005年威利期刊公司。
This study was designed to assess the influence of varied release kinetics of the osteogenic thrombin peptide TP508 from osteoconductive poly(propylene fumarate)based (PPF) composite scaffolds on bone formation in vivo. Four classes of scaffolds were constructed with different TP508 dosages (200, 100, or 0 mug) and release kinetics (large burst release, minimal burst release, or no release) and implanted in 15.0 mm segmental defects in rabbit radii. The animals were euthanized at 12 weeks and the implants were analyzed by light microscopy, histological scoring analysis, and histomorphometric analysis. Samples from all classes displayed bone growth within the pores of the scaffold near the edges of the defect. In areas where bone was not observed, the pores were filled with mostly fibrous tissue and exhibited minimal inflammatory response for all classes. In contrast to other scaffold classes, scaffolds containing a total dose of 200 mug TP508 and exhibiting a large burst release profile showed statistically more bone formation guided along the surface of the scaffold, with these scaffolds averaging 80% of the defect length bridged with bone compared to 10% or less bridged for the other scaffold classes. These results demonstrate that the extent of in vivo bone formation in response to controlled release from PPF-composite scaffolds is determined by the release kinetics of the incorporated osteogenic peptide. (C) 2005 Wiley Periodicals, Inc.