We have previously reported a novel polymeric delivery vehicle that is assembled via interaction between heparin and the vascular endothelial growth factor (VEGF). Here, the cell-responsiveness of this hydrogel including the delivery of VEGF in response to VEGFR-2 overexpressing PAE/KDR cells (porcine aortic endothelial cells (PAE) equipped with the transcript for the kinase insert domain receptor (KDR)), consequent erosion of the hydrogel matrix, and cellular response are highlighted. The release of VEGF and hydrogel erosion reached 100% only in the presence of PAE/KDR. The [PEG-LMWH/VEGF] hydrogel (PEG = poly(ethylene glycol), LMWH = low molecular weight heparin) correspondingly prompted increases in VEGFR-2 phosphorylation and proliferation of PAE/KDR cells. This study proves that growth factor-crosslinked hydrogels can liberate VEGF in response to specific receptors, causing gel erosion and desired cell responses. The promise of these approaches in therapeutic applications, including targeted delivery, is suggested.