The enhancement of VEGF-mediated angiogenesis by polycaprolactone scaffolds with surface cross-linked heparin.
The enhancement of VEGF-mediated angiogenesis by polycaprolactone scaffolds with surface cross-linked heparin.
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DOI：
10.1016/j.biomaterials.2010.11.038
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发表时间：
2011-03
期刊：
影响因子：
14
通讯作者：
Dunn, James C. Y.
中科院分区：
文献类型：
--
作者：
Singh, Shivani;Wu, Benjamin M.;Dunn, James C. Y.
本研究探讨了表面交联肝素对血管内皮生长因子（VEGF）介导的多孔聚己内酯（PCL）支架体内血管生成的影响。我们测试了这样一个假设，即用亚微米厚的固定化肝素层涂覆的支架递送VEGF会加速血管生成。保留的VEGF的生物活性通过其VEGF受体-2的磷酸化来证实。在小鼠皮下植入7天和14天后，负载有VEGF的肝素-PCL支架显示出显著更高的血管浸润，其穿过整个支架厚度（2 mm）。分别通过平滑肌细胞覆盖率和血管灌注性证实新形成血管的稳定性和功能。通过改变VEGF剂量和肝素厚度来评估单个组分的贡献。延长PCL支架上的交联反应导致更高的肝素含量、更厚的肝素层和更高的VEGF保留。虽然用VEGF观察到剂量依赖性血管生成反应，但对于给定剂量的VEGF，较高量的交联肝素并没有转化为血管生成的额外改善。在体内观察了固定化肝素和VEGF在促进血管生成方面的协同作用。
This study investigates the effect of surface cross-linked heparin on vascular endothelial growth factor (VEGF)-mediated angiogenesis in porous polycaprolactone (PCL) scaffolds in vivo. We tested the hypothesis that VEGF delivered by scaffolds coated with a sub-micron thick layer of immobilized heparin would accelerate angiogenesis. The bioactivity of retained VEGF was confirmed by its phosphorylation of VEGF receptor-2. After 7 and 14 days of subcutaneous implantation in mice, the heparin-PCL scaffolds loaded with VEGF displayed significantly higher infiltration of blood vessels which traversed the entire scaffold thickness (2 mm). The stability and function of the newly formed vessels were confirmed by smooth muscle cell coverage and vessel perfusability, respectively. The contribution of individual components was assessed by varying the VEGF dose and heparin thickness. Prolonging the cross-linking reaction on PCL scaffolds resulted in higher heparin content, thicker heparin layer, and higher VEGF retention. While a dose-dependent angiogenic response was observed with VEGF, higher amount of cross-linked heparin did not translate into additional improvement in angiogenesis for a given dose of VEGF. The synergism of immobilized heparin and VEGF in stimulating angiogenesis was observed in vivo.
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