Mechanisms of vascular endothelial growth factor-induced pathfinding by endothelial sprouts in biomaterials.
Mechanisms of vascular endothelial growth factor-induced pathfinding by endothelial sprouts in biomaterials.
复制标题
血管内皮生长因子诱导生物材料中内皮芽寻路的机制。
DOI：
10.1089/ten.tea.2011.0323
复制
发表时间：
2012
影响因子：
--
通讯作者：
Heilshorn,Sarah
中科院分区：
文献类型：
--
作者：
Shamloo,Amir;Xu,Hui;Heilshorn,Sarah
A critical property of biomaterials for use in regenerative medicine applications is the ability to promote angiogenesis, the formation of new vascular networks, to support regenerating tissues. Recent studies have demonstrated that a complex interplay exists between biomechanical and biochemical regulators of endothelial cell sprouting, an early step in angiogenesis. Here, we use a microfluidic platform to study the pathfinding behaviors induced by various stable vascular endothelial growth factor (VEGF) gradients during sprouting morphogenesis within biomaterials. Quantitative, time-lapse analysis of endothelial sprouting demonstrated that the ability of VEGF to regulate sprout orientation during several stages of sprouting morphogenesis (initiation, elongation, and turning navigation) was biomaterial dependent. Identical VEGF gradients induced different types of coordinated cell movements depending on the density of the surrounding collagen/fibronectin matrix. In denser matrices, sprouts were more likely to have an initial orientation aligned parallel to the VEGF gradient. In contrast, in less dense matrices, sprouts were more likely to initially misalign with the VEGF gradient; however, these sprouts underwent significant turning and navigation to eventually reorient to be parallel to the VEGF gradient. These less dense matrices required shallower VEGF gradients and demonstrated lower activating VEGF thresholds to induce proper sprout alignment and pathfinding. These results encourage the future use of microfluidic platforms to probe fundamental aspects of matrix effects on angiogenesis, to screen biomaterials for angiogenic potential, and to designex vivotissues with aligned vascular networks.
