Wyss Institute for Biologically Inspired Engineering, Harvard University, Cambridge, MA, USA.
Biomaterials. 2010 Feb;31(6):1235-41. doi: 10.1016/j.biomaterials.2009.10.052. Epub 2009 Nov 10.
Therapeutic angiogenesis relies on the delivery of angiogenic factors capable of reversing tissue ischemia. Polymeric materials that can provide spatial and temporal over vascular endothelial growth factor (VEGF) presentation provide clear benefit, but the influence of VEGF dose, temporal, and spatial presentation on the resultant angiogenic process are largely unknown. The influence of the temporal profile of VEGF concentration, dose, and the impact of VEGF spatial distribution on angiogenesis in in vitro models of angiogenesis and ischemic murine limbs was analyzed in this study. Importantly, a profile consisting of a high VEGF concentration initially, followed by a decreasing concentration over time was found to yield optimal angiogenic sprouting. A total VEGF dose 0.1 microg/g, when delivered with kinetics found to be optimal in vitro, provided a favorable therapeutic dose in murine hindlimb ischemia model, and distributing this VEGF dose in two spatial locations induces a higher level of vascularization and perfusion than a single location. These findings suggest that material systems capable of controlling and regulating the temporal and spatial presentation of VEGF maybe useful to achieve a robust and potent therapeutic angiogenic effect in vivo.
治疗性血管生成依赖于能够逆转组织缺血的血管生成因子的递送。能够提供血管内皮生长因子 (VEGF) 呈现的空间和时间的聚合物材料提供了明显的益处，但 VEGF 剂量、时间和空间分布对血管生成结果的影响在很大程度上尚不清楚。本研究分析了 VEGF 浓度的时间曲线、剂量以及 VEGF 空间分布对体外血管生成模型和缺血性鼠后肢血管生成的影响。重要的是，研究发现最初具有高 VEGF 浓度，随后浓度随时间降低的曲线能够产生最佳的血管生成发芽。当以在体外发现的最佳动力学传递时，0.1 微克/克的总 VEGF 剂量在鼠后肢缺血模型中提供了有利的治疗剂量，并且将这种 VEGF 剂量分布在两个空间位置比单个位置诱导更高水平的血管生成和灌注。这些发现表明，能够控制和调节 VEGF 的时空呈现的材料系统可能有助于在体内实现强大而有效的治疗性血管生成作用。
