Delayed administration of adenoviral BMP-2 vector improves the formation of bone in osseous defects
Delayed administration of adenoviral BMP-2 vector improves the formation of bone in osseous defects
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DOI：
10.1038/sj.gt.3302956
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发表时间：
2007-07-01
期刊：
影响因子：
5.1
通讯作者：
Evans, C. H.
中科院分区：
文献类型：
--
作者：
Betz, O. B.;Betz, V. M.;Evans, C. H.
在兔和大鼠模型中，携带人BMP-2 cDNA的腺病毒（Ad.BMP-2）的直接局部给药可愈合临界大小的股骨缺损。然而，结果是次优的，技术需要提供更可靠和统一的结果。为此，我们研究了Ad.BMP-2给药的时间是否影响缺损内矿化组织的形成。在28只Sprague道利大鼠股骨中制造临界尺寸的缺损。在手术中（第0天）或手术后24小时（第1天）、5天或10天，对动物病灶内单次经皮注射Ad.BMP-2（4 × 10（8）斑块形成单位）。术后8周行X线片、微型计算机断层扫描、双能X线骨密度仪和生物力学测试。放射学愈合的发生率显着增加时，管理的Ad.BMP-2被推迟到第5和10天，在这一点上86%的缺陷愈合。这些时间点也提供了更大的骨矿物质含量的缺损部位，并提高了愈合骨的平均机械强度。因此，将Ad.BMP-2的注射延迟至手术后5或10天，能够使更大百分比的临界尺寸的节段性缺损实现放射性愈合，产生具有增强的矿化和更大的机械强度的修复组织。
The direct, local, administration of adenovirus carrying human BMP-2 cDNA (Ad.BMP-2) heals critical-sized femoral bone defects in rabbit and rat models. However, the outcome is suboptimal and the technology needs to provide a more reliable and uniform outcome. To this end, we investigated whether the timing of Ad.BMP-2 administration influenced the formation of mineralized tissue within the defect. Criticalsized defects were created in the femora of 28 Sprague Dawley rats. Animals were injected intralesionally with a single, percutaneous injection of Ad.BMP-2 (4 x 10(8) plaque-forming units) either intraoperatively (day 0) or 24 h (day 1), 5 days or 10 days after surgery. The femora were evaluated 8 weeks after surgery by X-ray, microcomputed tomography, dual-energy X-ray absorptiometry and biomechanical testing. The incidence of radiological union was markedly increased when administration of Ad.BMP-2 was delayed until days 5 and 10, at which point 86% of the defects healed. These time points also provided greater bone mineral content within the defect site and improved the average mechanical strength of the healed bone. Thus, delaying the injection of Ad.BMP-2 until 5 or 10 days after surgery enables a greater percentage of critical-sized, segmental defects to achieve radiological union, producing a repair tissue with enhanced mineralization and greater mechanical strength.