Ennett Alessandra B, Kaigler Darnell, Mooney David J
Division of Engineering and Applied Sciences, Harvard University, Cambridge, Massachusetts, USA.
J Biomed Mater Res A. 2006 Oct;79(1):176-84. doi: 10.1002/jbm.a.30771.
The exposure duration and tissue distribution will likely dictate the success of vascular endothelial growth factor (VEGF) in therapeutic angiogenesis. We hypothesized that these variables can be regulated via the manner in which the VEGF is incorporated into polymer constructs (formed with a gas foaming technique) used for its delivery. VEGF was incorporated directly into poly(lactide-co-glycolide) (PLG) scaffolds or pre-encapsulated in PLG microspheres used to fabricate scaffolds. Protein release kinetics and tissue distribution were determined using iodinated VEGF. VEGF was positioned predominantly adjacent to scaffold pores when incorporated directly and was released rapidly (40-60% in 5 days). Pre-encapsulation led to the VEGF being more deeply embedded and resulted in a delayed release. Alterations in polymer composition, scaffold size, and matrix composition generated minor variations in release kinetics. In vivo, the released VEGF generated local protein concentrations above 10 ng/mL at distances up to 2 cm from the implant site for the 21 days of the experiment, with negligible release into the systemic circulation, and significantly enhanced local angiogenesis. These data indicate that VEGF can be administered in a sustained and localized fashion in vivo, and the timing of VEGF delivery can be altered with the mechanism of incorporation into polymer scaffolds used for its delivery.
暴露持续时间和组织分布可能决定血管内皮生长因子（VEGF）在治疗性血管生成中的成效。我们推测，这些变量可以通过VEGF掺入用于其递送的聚合物构建体（采用气体发泡技术形成）的方式来调节。VEGF被直接掺入聚丙交酯-乙交酯（PLG）支架中，或预先封装在用于制造支架的PLG微球中。使用碘化VEGF测定蛋白质释放动力学和组织分布。当直接掺入时，VEGF主要位于支架孔附近，并迅速释放（5天内释放40%-60%）。预先封装导致VEGF嵌入更深，并导致释放延迟。聚合物组成、支架尺寸和基质组成的改变在释放动力学上产生了微小变化。在体内，在实验的21天里，释放的VEGF在距植入部位2 cm范围内产生的局部蛋白质浓度高于10 ng/mL，进入体循环的释放量可忽略不计，并且显著增强了局部血管生成。这些数据表明，VEGF可以在体内以持续和局部的方式给药，并且VEGF递送的时间可以通过其掺入用于递送的聚合物支架的机制来改变。
