Neuronal production from induced pluripotent stem cells in self-assembled collagen-hyaluronic acid-alginate microgel scaffolds with grafted GRGDSP/Ln5-P4.

Self-assembled microgel functionalized with peptides was developed and applied to regenerate neurons from induced pluripotent stem cells (iPSCs). Collagen (COL), hyaluronic acid (HA), and alginate (ALG) were modified with methacrylic anhydride (MA), photocrosslinked for patterned particles, grafted with GRGDSP and Ln5-P4, and self-assembled to integrate the microgel into three-dimensional scaffolds. Physicochemical assessments revealed that the ternary microgel scaffolds had an optimal chemical composition at COLMA:HAMA:ALGMA=1:2:1. In fabricating cell-laden constructs, modified GRGDSP/Ln5-P4 in linear self-assembled scaffolds could significantly improve the entrapment efficiency and viability of iPSCs. In addition, GRGDSP/Ln5-P4 in the microgel constructs triggered the differentiation of iPSCs toward neurons, since the percentage of neurite-like cells could be higher than 98% after induction of nerve growth factor. Self-assembled microgel comprising COLMA, HAMA, ALGMA, and GRGDSP/Ln5-P4 may be promising in producing mature neural lineage from iPSCs, to provide better treatment for damaged nervous tissue.