Bone regeneration by modified gene-activated matrix: Effectiveness in segmental tibial defects in rats
Bone regeneration by modified gene-activated matrix: Effectiveness in segmental tibial defects in rats
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DOI：
10.1089/ten.2006.12.489
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发表时间：
2006-03-01
影响因子：
--
通讯作者：
Kasugai, S
中科院分区：
文献类型：
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作者：
Endo, M;Kuroda, S;Kasugai, S
基因激活基质(GAM)是一种基质，如含胶原蛋白的质粒载体，它编码一种蛋白质来刺激组织再生。在原有的GAM系统中，基因转移效率极低。我们最近报道了用钙磷沉淀物(CAP)修饰GAM可以提高基因转移的效率。本研究的目的是评估我们改良的GAM对组织再生的影响。我们制备了大鼠胫骨临界大小的节段性骨缺损，并移植了由牛胶原和编码人骨形成蛋白2的表达载体(BMP2)组成的GAM，带或不带帽。随后对胫骨进行了放射学、组织学和机械学检查。植入12mgBMP2的BMP2-帽-胶原蛋白在4周时桥接了骨缺损，6周时其强度与完整的胫骨相当。植入相同剂量BMP2的BMP2-胶原可较小程度地修复缺损区。单纯的胶原蛋白和空载的载体-帽-胶原蛋白都不能桥接缺损区。这些结果表明，我们修饰的带有CAP的GAM在比以前研究中使用的更低的质粒DNA剂量下具有潜在的组织再生效果。
Gene-activated matrix (GAM) is a matrix, such as collagen-containing plasmid vector, that encodes a protein to stimulate tissue regeneration. In the original GAM system, gene transfer efficiency was extremely low. We have recently reported that modifying GAM with calcium-phosphate precipitates (CaP) enhances the efficiency of gene transfer. The purpose of this study was to evaluate the effects of our modified GAM on tissue regeneration. We prepared critical size segmental bone defects in rat tibiae and transplanted GAM consisting of bovine atelocollagen and expression plasmid vector (bmp2), which encodes human BMP2, with or without CaP. The tibiae were later examined radiographically, histologically, and mechanically. Implantation of bmp2-CaP-collagen at 12 mu g bmp2 bridged the bone defect at 4 weeks, and the strength of the bone was comparable to that of an intact tibia at 6 weeks. Implantation of bmp2-collagen at the same dose of bmp2 bridged the defect to a smaller extent. Neither collagen alone nor vacant vector-CaP-collagen bridged the defect. These results indicate that our modified GAM with CaP has the potential to be effective in tissue regeneration at lower plasmid DNA doses than used in previous studies.