Department of Bioengineering, University of California, Los Angeles, CA 90095, USA.
Biomaterials. 2011 Mar;32(8):2059-69. doi: 10.1016/j.biomaterials.2010.11.038. Epub 2010 Dec 13.
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.
本研究考察了表面交联肝素对多孔聚己内酯（PCL）支架中血管内皮生长因子（VEGF）介导的血管生成的影响。我们假设，通过涂覆有亚微米厚固定化肝素层的支架来输送 VEGF 将加速血管生成。保留的 VEGF 的生物活性通过 VEGF 受体-2 的磷酸化来确认。在小鼠皮下植入 7 天和 14 天后，负载 VEGF 的肝素-PCL 支架显示出明显更高的血管渗透，这些血管贯穿整个支架厚度（2 毫米）。新形成的血管的稳定性和功能分别通过平滑肌细胞覆盖和血管灌注来确认。通过改变 VEGF 剂量和肝素厚度来评估各个组件的贡献。延长 PCL 支架上的交联反应会导致肝素含量增加、肝素层变厚和 VEGF 保留增加。虽然 VEGF 表现出剂量依赖性的血管生成反应，但对于给定剂量的 VEGF，更多量的交联肝素并不会转化为血管生成的额外改善。固定化肝素和 VEGF 在刺激血管生成方面的协同作用在体内得到了观察。
