Photoinitiator-free light-mediated crosslinking of dynamic polymer and pristine protein networks.

Light-based patterning of synthetic and biological hydrogels enables precise spatial and temporal control over the formation of chemical bonds. However, photoinitiators are typically used to generate free radicals, which are detrimental to human cells. Here, we report a photoinitiator- and radical-free method based on ortho-nitrobenzyl alcohol (oNBA) photolysis, which gives rise to highly reactive nitroso and benzaldehyde groups. Synthetic hydrogel and pristine protein networks can rapidly form in the presence of these photo-generated reactive species. Thiol -oNBA bonds yield dynamic hydrogel networks (DHNs) via N-semimercaptal linkages that exhibit thixotropy, stress relaxation, and on-demand reversible gel-to-liquid transitions, while amine-oNBA bonds can be exploited to crosslink pristine proteins, such as gelatin and fibrinogen, by targeting their primary amines. Since this approach does not require incorporation of photoreactive moieties along the backbone, the resulting crosslinked proteins are well suited for bioadhesives. Our photoinitiator-free platform provides a versatile approach for rapidly creating synthetic and biological hydrogels for applications ranging from tissue engineering to biomedical devices.