Recent developments in photodegradable (PD) hydrogels have allowed researchers to study cell behavior in response to spatial and temporal changes to the extracellular environment. To date, most PD hydrogel systems have been composed of PEG-based macromers that crosslink via end-linking gelation. PEG-based hydrogels, however, are not optimal for three-dimension cell culture, as they neither allow for cellular proliferation nor restructuring of the matrix. Unlike PEG-based hydrogels, gelatin, a naturally derived material, contains enzymatically degradable sites and cell binding domains, making it an attractive biomaterial for three-dimensional cell culture. To this end, researchers have modified gelatin to contain methacrylamide groups (GelMA).This allows the gels to be chemically crosslinked, rendering them stable at physiological temperatures. In this work, we develop a PD gelatin hydrogel system that is mechanically robust and can be easily produced in large quantities. While other researchers have attempted to produce PD gelatin hydrogels, the results have been limited and have been hampered by poor conjugation efficiency and poor solubility, leading to insufficient mechanical properties. To alleviate this complication, we chemically modify the gelatin with highly hydrophilic groups which, in turn, adjust the isoelectric point and charge density of the protein. This modification resulted in a highly soluble, PD-gelatin that could be crosslinked into a gel and subsequently degraded with exposure to light. These PD-gelatin gels exhibit mechanical properties similar to GelMA gels, but with the extra ability to be spatially and temporally patterned with light. Furthermore, we utilize a PD linkage with a low extinction coefficient. Thus, degradation along the path of light is uniform, allowing for a uniform mechanical environment in three-dimensional cell culture, not possible with any other PD-hydrogels. Photodegradation of the gels can be done either before cell seeding or in the presence of cells. We show that cells respond to both patterned structures and <i>in situ</i> softening of the network.

Mechanically robust photodegradable gelatin hydrogels for 3D cell culture and <i>in situ</i> mechanical modification

256th National Meeting (2018)

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Mechanically robust photodegradable gelatin hydrogels for 3D cell culture and in situ mechanical modification