Adeno-associated virus-coated allografts: a novel approach for cranioplasty.
Adeno-associated virus-coated allografts: a novel approach for cranioplasty.
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DOI：
10.1002/term.1594
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发表时间：
2012-11
影响因子：
3.3
通讯作者：
Gazit, Dan
中科院分区：
文献类型：
--
作者：
Ben Arav, Ayelet;Pelled, Gadi;Zilberman, Yoram;Kimelman-Bleich, Nadav;Gazit, Zulma;Schwarz, Edward M.;Gazit, Dan
关键词：
自体骨移植被认为是颅骨成形术的黄金标准，尽管它们会导致合并症。同种异体骨更容易获得，但成骨潜力较低，无法融入健康骨骼。此前，我们表明，通过用编码成骨基因的冻干重组腺相关病毒（rAAV）载体包被长骨同种异体移植物，可以增强成骨和骨整合。在本研究中，我们的目的是评估小鼠颅骨成形术模型中编码骨形态发生蛋白（BMP）–2的单链rAAV2载体（SS-rAAV-BMP2）或自互补假型载体（SC-rAAV-BMP2）包被的自体颅骨移植物和同种异体移植物的骨修复潜力。将移植物植入骨钙素/荧光素酶（Oc/Luc）转基因小鼠颅盖的严重缺损处，从而可以使用生物发光成像（BLI）纵向监测成骨活性。我们的结果表明，SC-rAAV-BMP2 包被的同种异体移植物的生物发光信号比 SS-rAAV-BMP2 包被的同种异体移植物大 40%（p<0.05），并且 SS-rAAV-BMP2 包被的同种异体移植物的生物发光信号与自体移植物或未包被的同种异体移植物的信号没有显着差异。微计算机断层扫描 (μCT) 证实，与 SS-rAAV-BMP2 组相比，SC-rAAV-BMP2 组的成骨显着增加 (p<0.05)，表明与其他测试的移植物相比，骨形成存在显着差异。此外，组织学分析显示自体移植物发生了广泛的重塑。总的来说，这些结果证明了使用 SC-rAAV-BMP2 涂层同种异体移植物进行颅面再生的可行性，这可能是修复严重颅面骨缺损的一种有吸引力的治疗解决方案。
Bone autografts are considered the gold standard for cranioplasty although they lead to comorbidity. Bone allografts are more easily obtained but have low osteogenic potential and fail to integrate into healthy bone. Previously, we showed that by coating long-bone allografts with freeze-dried recombinant adeno-associated virus (rAAV) vector encoding for an osteogenic gene, enhanced osteogenesis and bone integration were achieved. In this study our aim was to evaluate the bone repair potential of calvarial autografts and allografts coated with either single-stranded rAAV2 vector (SS-rAAV-BMP2) or self-complementary pseudotyped vector (SC-rAAV-BMP2) encoding for bone morphogenetic protein (BMP)–2 in a murine cranioplasty model. The grafts were implanted into critical defects in the calvariae of osteocalcin/luciferase (Oc/Luc) transgenic mice, which allowed longitudinal monitoring of osteogenic activity using bioluminescence imaging (BLI). Our results showed that the bioluminescent signal of the SC-rAAV-BMP2–coated allografts was 40% greater than that of the SS-rAAV-BMP2–coated allografts (p<0.05) and that the bioluminescent signal of the SS-rAAV-BMP2–coated allografts was not significantly different from the signals of the autografts or uncoated allografts. Micro–computed tomography (μCT) confirmed the significant increase in osteogenesis in the SC-rAAV-BMP2 group compared with the SS-rAAV-BMP2 group (p<0.05), indicating a significant difference in bone formation when compared with the other grafts tested. In addition, histological analysis revealed extensive remodeling of the autografts. Collectively, these results demonstrate the feasibility of craniofacial regeneration using SC-rAAV-BMP2–coated allografts, which may be an attractive therapeutic solution for repair of severe craniofacial bone defects.
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影响因子：
82.9
作者：
Bonadio, J;Smiley, E;Goldstein, S
通讯作者：
Goldstein, S
影响因子：
12.4
作者：
Koefoed, M;Ito, H;Schwarz, EM
通讯作者：
Schwarz, EM
DOI：
10.1302/0301-620x.41b1.160
发表时间：
1959-01-01
影响因子：
--
作者：
CHALMERS, J
通讯作者：
CHALMERS, J
影响因子：
3.6
作者：
Afifi, Ahmed M.;Gordon, Chad R.;Zins, James E.
通讯作者：
Zins, James E.
DOI：
10.1097/00001665-199001000-00011
发表时间：
1990-01-01
期刊：
The Journal of craniofacial surgery
影响因子：
--
作者：
Hollinger, J O;Kleinschmidt, J C
通讯作者：
Kleinschmidt, J C