Matrix‐Bound VEGF Mimetic Peptides: Design and Endothelial‐Cell Activation in Collagen Scaffolds

Abstract Long‐term survival and success of artificial tissue constructs depend greatly on vascularization. Endothelial‐cell (EC) differentiation and vasculature formation are dependent on spatiotemporal cues in the extracellular matrix that dynamically interact with cells; a process that is difficult to reproduce in artificial systems. Here, a novel bifunctional peptide is presented that mimics matrix‐bound vascular endothelial growth factor (VEGF) which 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. Spatial modification of collagen substrates is also shown with this peptide, which 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.