Poly(vinyl alcohol--itaconic acid) hydrogels grafted with several designed peptides for human pluripotent stem cell culture and differentiation into cardiomyocytes

• Published in: Journal of materials chemistry. B, Materials for biology and medicine Materials for biology and medicine, 2021-09, Vol.9 (37), p.7662-7673
• Main Authors: Sung, Tzu-Cheng, Lu, Ming-Wei, Tian, Zeyu, Lee, Henry Hsin-Chung, Pan, Jiandong, Ling, Qing-Dong, Higuchi, Akon
• Format: Article
• Language: English
• Subjects: Amino Acid Sequence; Amino acids; Animals; Cardiomyocytes; Cations; Cell adhesion; Cell culture; Cell differentiation; Cell Differentiation - drug effects; Cell proliferation; Cell Proliferation - drug effects; Chains; Differentiation; Grafting; Humans; Hydrogels; Hydrogels - chemistry; Hydrogels - pharmacology; Itaconic acid; Laminin; Laminin - chemistry; Mice; Mice, Inbred NOD; Mice, SCID; Myocytes, Cardiac - cytology; Myocytes, Cardiac - metabolism; Peptides; Peptides - chemistry; Photovoltaic cells; Pluripotency; Pluripotent Stem Cells - cytology; Pluripotent Stem Cells - metabolism; Polymers - chemistry; Polyvinyl Alcohol - chemistry; Segments; Stem cells; Succinates - chemistry; Surface Properties; Vitronectin; Xenografts; Zeta potential
• ISSN: 2050-750X; 2050-7518
• DOI: 10.1039/d1tb01555a

We developed poly(vinyl alcohol- co -itaconic acid) (PV) hydrogels grafted with laminin-derived peptides that had different joint segments and several specific designs, including dual chain motifs. PV hydrogels grafted with a peptide derived from laminin-β4 (PMQKMRGDVFSP) containing a joint segment, dual chain motif and cationic amino acid insertion could attach human pluripotent stem (hPS) cells and promoted high expansion folds in long-term culture (over 10 passages) with low differentiation rates, whereas hPS cells attached poorly on PV hydrogels grafted with laminin-α5 peptides that had joint segments with and without a cationic amino acid or on PV hydrogels grafted with laminin-β4 peptides containing the joint segment only. The inclusion of a cationic amino acid in the laminin-β4 peptide was critical for hPS cell attachment on PV hydrogels, which contributed to the zeta potential shifting to higher values (3-4 mV enhancement). The novel peptide segment-grafted PV hydrogels developed in this study supported hPS cell proliferation, which induced better hPS cell expansion than recombinant vitronectin-coated dishes (gold standard of hPS cell culture dishes) in xeno-free culture conditions. After long-term culture on peptide-grafted hydrogels, hPS cells could be induced to differentiate into specific lineages of cells, such as cardiomyocytes, with high efficiency. Human pluripotent stem cells can be successfully cultured on hydrogels grafted with laminin-β4 peptide having appropriate ζ potential, which have a joint segment, dual chain motif, and cationic amino acid insertion.