ABSTRACT Hydrogels prepared from gelatin are ideal for mimicking the extracellular matrix (ECM) owing to their inherent cell‐adhesive and protease‐labile peptide sequences. While gelatin is highly water‐soluble, it does not form the triple‐helical structure. As a result, physically crosslinked gelatin‐based hydrogels are only stable at low temperatures, precluding their use in 3D cell culture. Gelatin‐methacryloyl (GelMA) and gelatin‐norbornene (GelNB) have been developed to enable the stable crosslinking of gelatin‐based hydrogels via chain‐growth or step‐growth photopolymerization. However, most gelatin‐based hydrogels lack dynamically tunable properties unless macromers with dynamically crosslinkable motifs are used. Here, we integrate GelNB with dithiolane‐containing crosslinker poly(ethylene glycol)‐tetra‐lipoic acid (PEG4LA)‐for modular photo‐crosslinking of GelNB into hydrogels under cytocompatible light exposure (365 nm, 5 mW/cm 2 ) with a low photoinitiator concentration (1 m m LAP). Even under these mild reaction conditions, the stiffness of GelNB/PEG4LA hydrogels could be dynamically tuned by inducing dithiolane ring‐opening via secondary light exposure, thereby creating dynamic and cytocompatible hydrogels suitable for in situ encapsulation, culture, and differentiation of human induced pluripotent stem cells (hiPSCs).
Afolabi et al. (Sun,) studied this question.