Thermally Cured Gelatin-Methacryloyl Hydrogels Form Mechanically Modulating Platforms for Cell Studies

Gelatin methacryloyl (GelMA) is a polypeptide derived from the methacryloylation of gelatin and retains the thermoresponsive behavior of gelatin. When cooled, GelMA undergoes a sol–gel transition. By photo-cross-linking GelMA in a heated (“Hot”) or cooled (“Cold”) state, it results in a set of hydrogels with distinct properties. To date, the mechanical properties of these resulting hydrogels have not been fully elucidated. Here, we show that “Cold” hydrogels are viscoelastic, while “Hot” hydrogels are almost completely elastic. These features have remarkable implications for cell–substrate interactions in vitro: here, we show that fibroblasts, when cultured on these different substrates, adhere preferentially to Cold hydrogels. These results suggest that efficient cell adhesion requires specific mechanical properties of the substrate. This novel platform enables the precise control of different mechanical properties of GelMA by simply adjusting the cross-linking temperature, providing a flexible approach for the design of biologically inspired microenvironments in vitro.