A covalently modified hydrogel blend of hyaluronan-methyl cellulose with peptides and growth factors influences neural stem/progenitor cell fate

With the goal of controlling stem cell fate, for ultimate application in cell delivery, we synthesized a cell delivery vehicle comprised of an injectable hydrogel of hyaluronan (HA) and methyl cellulose (MC) wherein the MC is modified to allow bio-orthogonal coupling chemistry. Specifically, MC was modified using thiol-maleimide and biotin-streptavidin chemistry to covalently conjugate the cell adhesive peptide, glycine-arginine-glycine-aspartic acid-serine (GRGDS), and the oligodendrocyte-differentiating factor, recombinant platelet-derived growth factor A (rPDGF-A). NSPCs differentiated into significantly more oligodendrocytes when cultured in a HAMC hydrogel modified with both PDGF-A and GRGDS compared to controls of unmodified HAMC hydrogel and HAMC modified with only GRGDS. These results demonstrate both the ability to influence NSPC fate with immobilized growth factor and a platform technology for broad applicability in bioactive factor immobilization.