Protein Hydrogels: The Swiss Army Knife for Enhanced Mechanical and Bioactive Properties of Biomaterials

Biomaterials are dynamic tools with many applications: from the primitive use of bone and wood in the replacement of lost limbs and body parts, to the refined involvement of smart and responsive biomaterials in modern medicine and biomedical sciences. Hydrogels constitute a subtype of biomaterials built from water-swollen polymer networks. Their large water content and soft mechanical properties are highly similar to most biological tissues, making them ideal for tissue engineering and biomedical applications. The mechanical properties of hydrogels and their modulation have attracted a lot of attention from the field of mechanobiology. Protein-based hydrogels are becoming increasingly attractive due to their endless design options and array of functionalities, as well as their responsiveness to stimuli. Furthermore, just like the extracellular matrix, they are inherently viscoelastic in part due to mechanical unfolding/refolding transitions of folded protein domains. This review summarizes different natural and engineered protein hydrogels focusing on different strategies followed to modulate their mechanical properties. Applications of mechanically tunable protein-based hydrogels in drug delivery, tissue engineering and mechanobiology are discussed.