Vascular endothelial growth factor gene-activated matrix (VEGF165-GAM) enhances osteogenesis and angiogenesis in large segmental bone defects
Vascular endothelial growth factor gene-activated matrix (VEGF165-GAM) enhances osteogenesis and angiogenesis in large segmental bone defects
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DOI：
10.1359/jbmr.050701
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发表时间：
2005-11-01
影响因子：
6.2
通讯作者：
Richter, W
中科院分区：
文献类型：
--
作者：
Geiger, F;Bertram, H;Richter, W
简介：骨不连骨愈合不足的一个原因是缺乏血管形成。在与血管生成密切相关的骨骼发生中，血管内皮生长因子（VEGF）促进生长板的血管化和软骨向骨的转化。我们假设，基因活化基质（GAM），创建与质粒编码的人VEGF（165），涂在胶原海绵可以有效地加速骨愈合大段defects.Materials和Methods：六十新西兰白色兔接受了一个半径，这是充满了0.1或1毫克质粒DNA作为GAM的15毫米的临界尺寸的缺陷。每3周拍摄一次X线片。6或12周后，处死动物。通过mu CT扫描测量新骨。血管密度测定使用抗CD 31染色的内皮细胞在18个地区的利益，每implant.Results：支架和对照质粒显示没有缺陷愈合，而大多数的动物在VEGF组显示部分或全部骨再生。在VEGF组中发现了显著更多的骨，0.1 mg和1 mg组之间没有显著差异。内皮细胞免疫组化染色显示，6周后，VEGF组显示血管数量是对照组的2 - 3倍，内皮面积明显增大。手术后12周，血管化的数量减少，而更多的新骨detector.Conclusions：兔临界尺寸缺损的大小是适当的，产生萎缩性骨不连。我们发现VEGF（165）-GAM可以促进血管生成和骨生成，是诱导萎缩性骨不连愈合的合适工具。
Introduction: One reason for lack of bone healing in nonunions is the absence of vascularization. In skeletogenesis, which is tightly linked to angiogenesis, vascular endothelial growth factor (VEGF) promotes the vascularization of the growth plate and transformation of cartilage to bone. We postulate that a gene-activated matrix (GAM), created with a plasmid coding for human VEGF(165), coated on a collagen sponge could efficiently accelerate bone healing in large segmental defects.Materials and Methods: Sixty New Zealand white rabbits received a 15-mm critical size defect on one radius, which was filled with either 0.1 or 1 mg plasmid-DNA as GAM. Radiographs were obtained every 3 weeks. After 6 or 12 weeks, animals were killed. New bone was measured by mu CT scans. Vascularity was measured using anti-CD31 staining of endothelial cells in 18 regions of interest per implant.Results: Scaffold and control plasmid showed no defect healing, whereas most of the animals in the VEGF groups showed partial or total bone regeneration. Significantly more bone was found in the VEGF groups, with no significant differences between the 0.1- and 1-mg groups. Immunohistochemical staining of endothelial cells revealed that the VEGF groups showed two to three times the number of Vessels and a significantly larger endothelial area after 6 weeks. Twelve weeks after surgery, the amount of vascularization decreased, whereas more new bone was detectable.Conclusions: The rabbit critical size defect was appropriate in size to produce atrophic nonunions. We showed that angiogenesis and osteogenesis can be promoted by a VEGF(165)-GAM that is an appropriate tool to induce bone healing in atrophic nonunions.