Healing of segmental bone defects by direct percutaneous gene delivery: Effect of vector dose
Healing of segmental bone defects by direct percutaneous gene delivery: Effect of vector dose
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DOI：
10.1089/hum.2007.077
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发表时间：
2007-10-01
影响因子：
4.2
通讯作者：
Evans, Christopher H.
中科院分区：
文献类型：
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作者：
Betz, Volker M.;Betz, Oliver B.;Evans, Christopher H.
先前的研究已经证明了直接腺病毒BMP-2（Ad. BMP-2）基因递送以增强骨修复。尽管如此，在使用大鼠节段性缺损模型的研究中，还没有证明在所有动物中实现可靠的完全骨愈合是可能的。为了解决这个问题，我们评估了载体剂量对愈合的影响。在27只Sprague-Dawley大鼠的右侧股骨中创建临界尺寸的缺损。缺损处接受2.7 x 107（低剂量）、2.7 x 108（中剂量）或2.7 x 109（高剂量）空斑形成单位Ad的单次病灶内经皮注射。BMP-2 8周后，通过X线、双能X线骨密度仪、显微计算机断层扫描（mu CT）和组织学对股骨进行评估。高剂量的载体桥接100%，中剂量桥接11%，低剂量桥接25%的缺陷，如通过X射线和mu CT成像所评估的。接受高剂量载体的骨矿物质含量和骨体积明显高于接受低剂量载体的两组。在组织学上，用高剂量治疗的缺损由骨小梁和少量软骨填充，而大面积的纤维组织和软骨保留在接受较低剂量的缺损中。然而，新形成的骨缺乏天然骨的结构组织，这表明需要进一步成熟。
Previous studies have demonstrated the ability of direct adenoviral BMP-2 (Ad. BMP-2) gene delivery to enhance bone repair. Nevertheless, in studies using a rat segmental defect model, it has not proved possible to achieve reliably full osseous union in all animals. To address this issue, we evaluated the effect of vector dose on healing. Critical-size defects were created in the right femora of 27 Sprague-Dawley rats. The defects received a single, intralesional, percutaneous injection of 2.7 x 107 (low dose), 2.7 x 108 (medium dose), or 2.7 x 109 (high dose) plaque-forming units of Ad. BMP-2. After 8 weeks, femora were evaluated by X-ray, dual-energy X-ray absorptiometry, microcomputed tomography (mu CT), and histology. The high dose of vector bridged 100%, the medium dose 11%, and the low dose 25% of the defects, as evaluated by X-ray and mu CT imaging. Bone mineral content and bone volume of the defects receiving the high dose of vector were significantly higher than those of both groups receiving lower doses. Histologically, defects treated with the high dose were filled by trabecular bone and small amounts of cartilage, whereas large areas of fibrous tissue and cartilage remained in the defects receiving lower doses. However, the newly formed bone lacked the structural organization of native bone, suggesting that further maturation is necessary.