Matrix-Bound VEGF Mimetic Peptides: Design and Endothelial Cell Activation in Collagen Scaffolds.
Matrix-Bound VEGF Mimetic Peptides: Design and Endothelial Cell Activation in Collagen Scaffolds.
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DOI：
10.1002/adfm.201101163
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发表时间：
2011-11-22
影响因子：
19
通讯作者：
Yu SM
中科院分区：
文献类型：
--
作者：
Chan TR;Stahl PJ;Yu SM
人工组织构建体的长期存活和成功在很大程度上取决于血管化。内皮细胞（EC）的分化和血管形成依赖于细胞外基质中的时空线索，动态地与细胞相互作用，这是一个难以在人工系统中重现的过程。在这里，我们提出了一种新的双功能肽，模拟基质结合的血管内皮生长因子（VEGF），可用于编码空间控制的胶原支架血管生成信号。该肽由先前报道通过独特的杂交机制与I型胶原结合的胶原模拟结构域和具有促血管生成活性的VEGF模拟结构域组成。圆二色性和胶原蛋白结合研究证实了三螺旋结构和胶原蛋白模拟结构域的胶原蛋白结合亲和力，EC培养研究证明了肽作为2D和3D胶原蛋白支架中的基质结合因子诱导内皮细胞形态发生和网络形成的能力。我们还显示了空间修饰的胶原蛋白底物与这种肽，允许本地EC激活和网络形成。这些结果表明，该肽可用于在胶原支架中呈现空间定向的血管生成线索，这可能对工程化有组织的微血管系统有用。
Long term survival and success of artificial tissue constructs depend greatly on vascularization. Endothelial cell (EC) differentiation and vasculature formation are dependent on spatio-temporal cues in the extracellular matrix that dynamically interact with cells, a process difficult to reproduce in artificial systems. Here we present a novel bifunctional peptide that mimics matrix-bound vascular endothelial growth factor (VEGF) and can be used to encode spatially controlled angiogenic signals in collagen scaffolds. The peptide is comprised of a collagen mimetic domain that was previously reported to bind to type I collagen by a unique hybridization mechanism, and a VEGF mimetic domain with pro-angiogenic activity. Circular dichroism and collagen binding studies confirm the triple helical structure and the collagen binding affinity of the collagen mimetic domain, and EC culture studies demonstrate the peptide’s ability to induce endothelial cell morphogenesis and network formation as a matrix-bound factor in 2D and 3D collagen scaffolds. We also show spatial modification of collagen substrates with this peptide that allows localized EC activation and network formation. These results demonstrate that the peptide can be used to present spatially directed angiogenic cues in collagen scaffolds, which may be useful for engineering organized microvasculature.