Rapid hydrogel formation via tandem visible light photouncaging and bioorthogonal ligation.

The formation of benign polymer scaffolds in water using green-light-reactive photocages is described. These efforts pave an avenue toward the fabrication of synthetic scaffolds that can facilitate the study of cellular events for disease diagnosis and treatment. First, a series of boron dipyrromethene (BODIPY) photocages with nitrogen-containing nucleophiles were examined to determine structure-reactivity relationships, which resulted in a >1,000× increase in uncaging yield. Subsequently, photoinduced hydrogel formation in 90 wt % water was accomplished via biorthogonal carbonyl condensation using hydrophilic polymer scaffolds separately containing BODIPY photocages and ortho-phthalaldehyde (OPA) moieties. Spatiotemporal control is demonstrated with light on/off experiments to modulate gel stiffness and masking to provide <100 μm features. Biocompatability of the method was shown through pre-/post-crosslinking cell viability studies. Short term, these studies are anticipated to guide translation to emergent additive manufacturing technology, which, longer term, will enable the development of 3D cell cultures for tissue engineering applications.