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Enzymes are a class of protein that catalyze a wide range of chemical reactions, including the cleavage of specific peptide bonds. They are expressed in all cell types, play vital roles in tissue development and homeostasis, and in many diseases, such as cancer. Enzymatic activity is tightly controlled through the use of inactive pro-enzymes, endogenous inhibitors and spatial localization. Since the presence of specific enzymes is often correlated with biological processes, and these proteins can directly modify biomolecules, they are an ideal biological input for cell-responsive biomaterials. These materials include both natural and synthetic polymers, cross-linked hydrogels and self-assembled peptide nanostructures. Within these systems enzymatic activity has been used to induce biodegradation, release therapeutic agents and for disease diagnosis. As technological advancements increase our ability to quantify the expression and nanoscale organization of proteins in cells and tissues, as well as the synthesis of increasingly complex and well-defined biomaterials, enzyme-responsive biomaterials are poised to play vital roles in the future of biomedicine.

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