Wavelength‐Dependent Stiffening of Hydrogel Matrices via Redshifted [2+2] Photocycloadditions

Hydrogels with on‐demand tunable mechanical properties within sensitive biological environments are of critical importance for examining cellular responses to cell culture platforms. Herein, the first bio‐orthogonal hydrogel that can be formed and subsequently tuned in its mechanical properties by simply switching different wavelengths of visible light (i.e., 455 and 420 nm) is reported. Specifically, both the initial hydrogelation and the tuning of the mechanical properties can be fully decoupled and selectively initiated by different colors of light. Sparing the need for any catalysts, the development of such a dual wavelength selective hydrogel for biological applications spans four levels: First, the development of the until today most redshifted photocycloaddition to allow for the selective initiation of only one photoreaction; second, the investigation of its wavelength‐dependent ligation efficiency; third, translation of the ligation chemistry into a hydrogelator, and fourth, establishing a biocompatible hydrogel platform for applications in biomaterials engineering including detachment of fibroblasts from 2D culture areas or primary 3D culture of human mesenchymal stem cells. The introduced platform technology enables the fabrication of a hydrogel of predefined mechanical properties exclusively with visible light.