Growth Factor Mediated Assembly of Cell Receptor-Responsive Hydrogels

Abstract

The design of materials in which assembly, mechanical response, and biological properties are controlled by protein-polysaccharide interactions may mimic the biological environment, be responsive to appropriate biological cues, and find use in many biomedical applications. Here we report the assembly of hydrogels via the noncovalent interaction of heparin-functionalized, star-PEG polymers and the therapeutically relevant, heparin-binding protein VEGF (vascular endothelial growth factor). The viscoelastic properties of these hydrogels, and the specificity of VEGF in crosslinking, were assessed via laser tweezer microrheology. The receptor-mediated delivery of VEGF, with concurrent erosion of the hydrogels, was indicated via radiometry assays of the hydrogels in the presence of VEGFR-2-modified particles, and the specificity of this interaction was indicated by a lack of erosion of the hydrogels when incubated with particles modified with a protein lacking affinity for VEGF. The VEGF delivered from the hydrogels is bioactive as assessed via cell proliferation and live/dead assays. These results indicate the potential for targeted delivery of growth factors and erosion of hydrogels on the basis of ligand-receptor interactions that occur between cells and the extracellular matrix. The therapeutic relevance of other dimeric heparin-binding growth factors, as well as opportunities for designing peptides with specific affinities and therapeutic action, suggests broader opportunities for these strategies in the production of responsive matrices for biomedical applications.