Dual peptide-presenting hydrogels for controlling the phenotype of PC12 cells

Controlling the cell-matrix interaction is a critical factor in the design and fabrication of tissue engineering scaffolds. A particular peptide sequence, Arg-Gly-Asp (RGD peptide), is often used as an adhesion ligand in the engineering of different types of tissues. While in some cases this has been adequate, the use of multiple ligands may be required for the successful engineering of some tissue types. We hypothesized that hydrogels presenting both the RGD peptide and the YIGSR peptide (Tyr-Ile-Gly-Ser-Arg) could successfully regulate the phenotype of PC12 cells, thereby providing a new platform for effective tissue engineering applications. We prepared alginate hydrogels modified with both RGD and YIGSR peptides at several different bulk ligand densities and determined the ways in which PC12 cells can respond to them in vitro. We demonstrate that alginate hydrogels presenting both RGD and YIGSR peptides successfully regulate the proliferation, morphological change, and neuronal differentiation of PC12 cells in vitro. Successful adhesion and proliferation of PC12 cells were dependent on the bulk density of RGD peptides, while neuronal differentiation was significantly enhanced by increasing the YIGSR density. These results suggest that hydrogels presenting multiple adhesion ligands offer many useful applications in tissue engineering approaches.