Cytocompatible Click-based Hydrogels with Dynamically-Tunable Properties Through Orthogonal Photoconjugation and Photocleavage Reactions

To provide insight as to how cells receive information from their external surroundings, synthetic hydrogels have emerged as systems for assaying cell function in well-defined microenvironments where single cues can be introduced and subsequent effects individually elucidated. However, as the field seeks to answer more complex biological questions, advanced material systems are needed that allow dynamic alteration of the 3D cellular environment with orthogonal reactions that enable multiple levels of control of biochemical and biomechanical signals. Here, we sought to synthesize one such 3D culture system using cytocompatible and wavelength-specific photochemical reactions to create hydrogels that allow orthogonal and dynamic control of the material properties through independent spatiotemporally-regulated photocleavage of crosslinks and photoconjugation of pendant functionalities. Results demonstrate the versatile nature of the chemistry to create programmable niches to study and direct cell function by modifying the local hydrogel environment.