Near-infrared-light regulated angiogenesis in a 4D hydrogel

Light-responsive hydrogels are useful platforms to study cellular responses. Current photosensitive motifs need UV light to be activated, which is intrinsically cytotoxic and has a low penetration depth in tissues. Herein we describe a strategy for near-infrared (NIR) controlled activation of cellular processes (3D cell spreading and angiogenesis) by embedding upconverting nanoparticles (UCNPs) in a hydrogel modified with light-activatable cell adhesive motifs. The UCNPs can convert NIR light (974 nm) into local UV emission and activate photochemical reactions on-demand. Such optoregulation is spatially controllable, dose-dependent and can be performed at different timepoints of the cell culture without appreciable photodamage of the cells. HUVEC cells embedded in this hydrogel can form vascular networks at predefined geometries determined by the irradiation pattern. The penetration depth of NIR light enabled activation of the angiogenesis response through skin tissue with a thickness of 2.5 mm. Our strategy opens a new avenue for 4D cell cultures, with the potential to be extended to dynamically manipulate cell-matrix interactions and derived cellular processes in vivo.