A Modular Approach to Sensitized Two‐Photon Patterning of Photodegradable Hydrogels

Photodegradable hydrogels have emerged as useful platforms for research on cell function, tissue engineering, and cell delivery as their physical and chemical properties can be dynamically controlled by the use of light. The photo‐induced degradation of such hydrogel systems is commonly based on the integration of photolabile o‐nitrobenzyl derivatives to the hydrogel backbone, because such linkers can be cleaved by means of one‐ and two‐photon absorption. Herein we describe a cytocompatible click‐based hydrogel containing o‐nitrobenzyl ester linkages between a hyaluronic acid backbone, which is photodegradable in the presence of cells. It is demonstrated for the first time that by using a cyclic benzylidene ketone‐based small molecule as photosensitizer the efficiency of the two‐photon degradation process can be improved significantly. Biocompatibility of both the improved two‐photon micropatterning process as well as the hydrogel itself is confirmed by cell culture studies. Sensitized micropatterning of photodegradable hydrogels by means of two‐photon irradiation is possible. The efficiency of the photoscission of o‐nitrobenzyl ester linkages is enhanced by the modular addition of a two‐photon active small molecule to a preformed hyaluronic acid based hydrogel. Biocompatibility of the improved two‐photon micropatterning process as well as the hydrogel is confirmed by cell culture studies.