Protocol for the synthesis and activation of hydrogels with photocaged oligonucleotides.

Hydrogels with spatial-temporal control over chemical and physical properties allow for the creation of cellular niches with controllable properties that better mimic tissue environments. Here, we present a protocol for synthesizing hydrogels incorporating photocaged oligonucleotides that can be activated with non-ultraviolet (UV) wavelengths. We detail the synthesis of bulk hydrogels and spatially defined hydrogels with different chemical functionalities that all share common photocaged DNA. Furthermore, we describe conditions for activating photocaged DNA to capture complementary oligonucleotides. For complete details on the use and execution of this protocol, please refer to Mathis et al.(1).