Biohybrid materials combining synthetic polymers with biological components are highly suited for tissue engineering in order to emulate the behavior of natural materials such as the extracellular matrix (ECM). In order to allow for an optimal cell-material interplay, the physical and biological parameters of the artificial matrix need to be dynamically remodeled during cultivation. Current tissue engineering concepts are mainly based on passive remodeling mechanisms including the degradation of the hydrogel and the release of incorporated biomolecules and therefore do not enable external adjustment of cultivation conditions. We present a novel hydrogel material that is able to serve as a cell growth matrix, whose degradation and presentation of cell-interacting biomolecules can be externally controlled by the addition of a pharmacological substance. The hydrogel is based on branched polyethylene glycol that is covalently decorated with the aminocoumarin-antibiotic switchable gyrase B protein conferring stimulus-responsive degradation. ECM properties were conferred to the hydrogels with cell attachment motifs and a general approach for the incorporation and inducible release of therapeutic biomolecules. This smart biohybrid material has the potential to serve as a next-generation tissue engineering device which allows for dynamic external adjustment of the physical and biological parameters, resulting in optimally controlled tissue formation.