Dual delivery of an angiogenic and an osteogenic growth factor for bone regeneration in a critical size defect model.
Dual delivery of an angiogenic and an osteogenic growth factor for bone regeneration in a critical size defect model.
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DOI：
10.1016/j.bone.2008.06.019
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发表时间：
2008-11
期刊：
影响因子：
4.1
通讯作者：
Mikos, Antonios G.
中科院分区：
文献类型：
--
作者：
Patel, Zarana S.;Young, Simon;Tabata, Yasuhiko;Jansen, John A.;Wong, Mark E. K.;Mikos, Antonios G.
关键词：
本研究探讨了血管内皮生长因子(VEGF)和骨形态发生蛋白-2(BMP-2)联合应用对大鼠颅骨临界大小缺损区骨再生的影响。用血管内皮细胞生长因子(12μg)、骨形态发生蛋白-2(2μg)、血管内皮生长因子(12μg)和骨形态发生蛋白-2(2μg)和明胶微粒释放生长因子作为支架材料。将这些支架植入8 mm大鼠颅骨临界大小的缺损处(每组n=8~9)。术后4周和12周取材，通过显微CT和组织学评分分析对种植体进行评价。此外，4周龄的动物被灌流一种不透射线的材料，以可视化和量化血管形成。组织学分析显示，在4周时，所有组的多孔性支架体积的大部分都被血管化的纤维组织所填充，但此时双释放组的骨形成最为丰富。12周时，双释放组和BMP-2组均可见支架孔内及支架外表面有大量骨形成，类骨质分泌和矿化明显，新生骨经常与支架界面紧密或直接接触。MicroCT结果显示，4周时各组间血管形成无显著差异(血管体积的4%)，但双释放组的骨形成显著高于其他组(16.1±9.2%骨体积)。12周时，双释放组和BMP-2组的骨形成(39.7±14.1%和37.4±18.8%骨体积)明显高于VEGF组和空白支架(6.3±4.8%和7.8±7.1%骨体积)。这项工作表明，在4周时，双重输送血管内皮生长因子和骨形态发生蛋白-2对骨形成有协同作用，并提示这两种生长因子在早期骨再生中的相互作用。对于所研究的剂量，结果表明，添加血管内皮生长因子并不影响BMP-2在12周时实现的骨形成量；然而，他们也表明，与单独使用BMP-2相比，这两种生长因子都可以促进临界大小的缺损区的骨桥接和愈合。
This study investigated the effects of dual delivery of vascular endothelial growth factor (VEGF) and bone morphogenetic protein-2 (BMP-2) for bone regeneration in a rat cranial critical size defect. Four groups of scaffolds were generated with VEGF (12 μg), BMP-2 (2 μg), both VEGF (12 μg) and BMP-2 (2 μg), or no growth factor released from gelatin microparticles incorporated within the scaffold pores. These scaffolds were implanted within an 8 mm rat cranial critical size defect (n = 8–9 for each group). At 4 and 12 weeks, implants were retrieved and evaluated by microcomputed tomography (microCT) and histological scoring analysis. Additionally, 4 week animals were perfused with a radiopaque material to visualize and quantify blood vessel formation. Histological analysis revealed that for all groups at 4 weeks, a majority of the porous scaffold volume was filled with vascularized fibrous tissue; however, bone formation appeared most abundant in the dual release group at this time. At 12 weeks, both dual release and BMP-2 groups showed large amounts of bone formation within the scaffold pores and along the outer surfaces of the scaffold; osteoid secretion and mineralization were apparent, and new bone was often in close or direct contact with the scaffold interface. MicroCT results showed no significant difference among groups for blood vessel formation at 4 weeks (<4% blood vessel volume); however, the dual release group showed significantly higher bone formation (16.1±9.2% bone volume) than other groups at this time. At 12 weeks, dual release and BMP-2 groups exhibited significantly higher bone formation (39.7 ± 14.1% and 37.4 ± 18.8% bone volume, respectively) than either the VEGF group or blank scaffolds (6.3 ± 4.8% and 7.8 ± 7.1% bone volume, respectively). This work indicates a synergistic effect of the dual delivery of VEGF and BMP-2 on bone formation at 4 weeks and suggests an interplay between these growth factors for early bone regeneration. For the doses investigated, the results show that the addition of VEGF does not affect the amount of bone formation achieved by BMP-2 at 12 weeks; however, they also indicate that delivery of both growth factors may enhance bone bridging and union of the critical size defect compared to delivery of BMP-2 alone.
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