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负载重组人骨形态发生蛋白-2的无抗原牛松质骨用于山羊模型胫骨骨缺损修复

Antigen-free bovine cancellous bone loaded with recombinant human bone morphogenetic protein-2 for the repair of tibial bone defects in goat model.

作者信息

Li Donghai, Deng Liqing, Yang Zhouyuan, Xie Xiaowei, Kang Pengde, Tan Zhen

机构信息

Department of Orthopaedics, West China Hospital, Sichuan University, Chengdu, People's Republic of China.

Department of Orthopaedics of Cheng Ban hospital, the Branch of West China Hospital, Sichuan University, Chengdu, People's Republic of China.

出版信息

J Biomater Appl. 2016 Apr;30(9):1322-33. doi: 10.1177/0885328215627796. Epub 2016 Jan 21.

DOI:10.1177/0885328215627796
PMID:26801475
Abstract

Antigen-free bovine cancellous bone has good performances of porous network structures and mechanics with antigen extracted. To develop a bioactive scaffold for enhancing bone repair and evaluate its biological property, rhBMP-2 loaded with antigen-free bovine cancellous bone was used to treat tibial bone defect. Twenty-four healthy adult goats were chosen to establish goat defects model and randomly divided into four groups. The goats were treated with rhBMP-2/antigen-free bovine cancellous bone scaffolds (group A), autogenous cancellous bone graft (group B), porous tricalciumphosphate scaffolds (group C) and nothing (group D). Animals were evaluated with radiological and histological methods at 4, 8 and 12 weeks after surgery. The gray value of radiographs was used to evaluate the healing of the defects, which revealed that the group A had a better outcome of defect healing compared with group C at 4, 8 and 12 weeks, respectively (p < 0.05), while the difference between groups A and B was without significance at each time (p > 0.05). The newly formed bone area was calculated from histological sections, and the results indicated that the amount of new bone in group A increased significantly compared with that in group C (p < 0.05) but was similar to that in group B (p > 0.05) at 4, 8 and 12 weeks, respectively. In addition, the expression of collagen I and vascular endothelial growth factor by real-time polymerase chain reaction at 12 weeks in group A was significantly higher than that in group C (p = 0.034, p = 0.032, respectively), but no significant differences were found when compared with that in group B (p = 0.36, p = 0.54, respectively). At the same time, group C presented better results than group D on bone defects healing. Therefore, the composites of antigen-free bovine cancellous bone loaded with rhBMP-2 have a good osteoinductive activity and capacity to promote the repair of bone defects.

摘要

脱抗原牛松质骨经抗原提取后具有良好的多孔网络结构和力学性能。为开发一种促进骨修复的生物活性支架并评估其生物学特性,采用负载重组人骨形态发生蛋白-2(rhBMP-2)的脱抗原牛松质骨治疗山羊胫骨骨缺损。选取24只健康成年山羊建立骨缺损模型,并随机分为四组。分别用rhBMP-2/脱抗原牛松质骨支架(A组)、自体松质骨移植(B组)、多孔磷酸三钙支架(C组)处理,空白对照组(D组)不做处理。术后4、8和12周采用影像学和组织学方法对动物进行评估。利用X线片灰度值评估骨缺损愈合情况,结果显示,术后4、8和12周时,A组骨缺损愈合效果分别显著优于C组(p<0.05),而A组与B组在各时间点差异均无统计学意义(p>0.05)。通过组织学切片计算新形成骨面积,结果表明,术后4、8和12周时,A组新骨量较C组显著增加(p<0.05),但与B组相近(p>0.05)。此外,术后12周时,A组I型胶原蛋白和血管内皮生长因子的实时聚合酶链反应表达水平显著高于C组(分别为p=0.034,p=0.032),但与B组比较差异无统计学意义(分别为p=0.36,p=0.54)。同时,C组骨缺损愈合情况优于D组。因此,负载rhBMP-2的脱抗原牛松质骨复合材料具有良好的骨诱导活性和促进骨缺损修复的能力。

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