The promotion of microvasculature formation in poly(ethylene glycol) diacrylate hydrogels by an immobilized VEGF-mimetic peptide

Abstract Microvascularization of tissue engineered constructs was achieved by utilizing a VEGF-mimicking peptide, QK, covalently bound to a poly(ethylene glycol) hydrogel matrix. The 15-amino acid peptide, developed by D’Andrea et al., was modified with a PEG-succinimidyl ester linker on the N-terminus of the peptide, then photocrosslinked onto the surface or throughout PEG hydrogels. PEGylation of the peptide increased its solubility and bioactivity, as evidenced by endothelial cell proliferation. PEG-QK showed equal or superior ability to promote angiogenesis in vitro , on the surface of hydrogels and within three-dimensional collagenase-degradable hydrogels, compared to RGDS only or PEG-VEGF hydrogels. Endothelial cells were shown to form tubule structures, migrate, and make cell–cell contacts in response to covalently-bound PEG-QK. In vivo in a mouse cornea micropocket angiogenesis assay, PEG-QK hydrogels promoted more complete coverage of host microvasculature within the hydrogel. PEG-QK was shown to enhance vessel branch points and vessel density as well as space filling properties of fractal dimension and lacunarity. This report shows the ability to promote angiogenesis in tissue engineered constructs using a covalently-bound small peptide rather than a large protein and may point to an advance in designing biomimetic cellular environments.