Cell responsive materials are instrumental to regenerative therapies. Here, we report about a novel biohybrid hydrogel that consists of heparin and peptide-conjugated star-shaped poly(ethylene glycol), crosslinked by peptide units that combine matrix metalloproteinase (MMP) sensitivity and cell adhesive modules. Taking advantage of the high affinity of vascular endothelial growth factor to heparin, we illustrate the applicability of our hydrogels as a novel system that is supportive of cellular remodeling and three-dimensional migration of human endothelial cells.