Enzyme‐Assisted Hydrogel Formation for Tissue Engineering Applications

Hydrogels are three-dimensional (3D) scaffolds able to embed cells and deliver biomolecules to promote tissue repair. These 3D matrices provide a temporary support to cells by mimicking natural tissue microenvironments and endow mechanical and biochemical functionalities to drive cell function on tissue growth, repair, and/or regeneration. Enzymatic tools are gaining considerable interest as an effective and green synthetic route that promote chemical and physical interactions between gel components. In enzymatically cross-linked hydrogels, enzymes catalyze the formation of covalent bonds between precursors to generate porous 3D structures. The mechanical strength and gelation rates of the scaffolds are modulated by the activity and type of enzyme. On the other hand, in enzyme-instructed self-assembling, the catalytic reaction modifies the hydrophobicity of the precursors. Changes on the amphiphilicity of these enzyme substrate precursors prompt their self-assembling through dynamic and reversible noncovalent interactions to produce higher ordered structures that further entangle into 3D networks. Both enzymatic approaches generate gel matrices compatible with the in situ integration of bioactive agents or cells. In this book chapter, different enzyme-assisted gelation strategies for tissue engineering (TE) and regenerative medicine applications will be reviewed considering precursors, enzyme-catalyzed reactions, and cross-linking interactions.