Chemoselective peptide functionalization of starPEG-GAG hydrogels

Glycosaminoglycan (GAG)-based hydrogels gain increasing interest in regenerative therapies. To support specific applications, the biomolecular functionality of gel matrices needs to be customized via conjugation of peptide sequences that mediate cell adhesion, expansion and differentiation. Herein, we present an orthogonal strategy for the formation and chemoselective functionalization of starPEG-GAG hydrogels, utilizing the uniform and specific conjugation of peptides and GAGs for customizing the resulting materials. The introduced approach was applied for the incorporation of three different types of RGD peptides to analyze the influence of peptide sequence and conformation on adhesion and morphogenesis of endothelial cells (ECs) grown on the peptide-containing starPEG-GAG hydrogels. The strongest cellular response was observed for hydrogels functionalized with cycloRGD followed by linear forms of RGDSP and RGD, showing that morphogenesis and growth rate of ECs is controlled by both type and quantity of the conjugated peptides.