Sustained Release of Proteins Using Region-Specific Tunable Degradability in Hydrogels through 3D Photopatterning and Complimentary Labile Bond Chemistry

Light-triggered chemical reactions have demonstrated great potential for advanced cell guidance, on-demand release of therapeutics, and complex patterning in four dimensions. Current strategies rely on the cleavage of a light sensitive bond, while several protein and therapeutic release systems are designed using a hydrolytically labile bond. To bridge the gap between externally controlled light regulated transformations and intrinsically controlled hydrolytically labile bonds, a new family of light-triggered photocages that upon conjugation to target proteins form more or less hydrolytically (un)stable imine, hydrazone, and oxime bonds is reported. The three photocages follow a dose-dependent relationship using ultraviolet and near-infrared radiation and the one- and two-photon uncaging can be controlled in discrete volumes down to at least 10 µm precision. Upon photoirradiation, the exposed latent amino-, hydrazino-, and hydroxylamino-moieties readily react with a variety of proteins, and complimentary sustained release can be achieved. The relative release rate of imine-, hydrazone-, and oxime-bound proteins enable control over cell fate on hydrogels using two neuroblastoma cell lines. These results are anticipated to open new avenues for advanced materials where region-specifical degradability is central, such as for complex protein photopatterns, cell-guided hydrogels, and for programmable materials using photomediated dynamic covalent chemistry and photoclick chemistry.