Soft, strong, tough, and durable protein-based fiber hydrogels

Load-bearing soft tissues normally show J-shaped stress-strain behaviors with high compliance at low strains yet high strength at high strains. They have high water content but are still tough and durable. By contrast, naturally derived hydrogels are weak and brittle. Although hydrogels prepared from synthetic polymers can be strong and tough, they do not have the desired bioactivity for emerging biomedical applications. Here, we present a thermomechanical approach to replicate the combinational properties of soft tissues in protein-based photocrosslinkable hydrogels. As a demonstration, we create a gelatin methacryloyl fiber hydrogel with soft tissue-like mechanical properties, such as low Young's modulus (0.1 to 0.3 MPa), high strength (1.1 & PLUSMN; 0.2 MPa), high toughness (9,100 & PLUSMN; 2,200 J/m3), and high fatigue resistance (2,300 & PLUSMN; 500 J/m2). This hydrogel also resembles the biochemical and architectural properties of native extracellular matrix, which enables a fast formation of 3D interconnected cell meshwork inside hydrogels. The fiber architecture also regulates cellular mechanoresponse and supports cell remodeling inside hydrogels. The integration of tissue-like mechanical properties and bioactivity is highly desirable for the next-generation biomaterials and could advance emerging fields such as tissue engineering and regenerative medicine.SignificanceEmerging biomedical applications, such as tissue engineering and artificial tissues, require implant materials to be both biologically and mechanically compatible with living tissues. However, the combination of these two properties has not been achieved in current material systems. Naturally derived materials carry the essential biological features of tissues but tend to be weak and brittle. Whereas synthetic polymers can replicate the mechanical properties of tissues but often lack the ability to support and direct live cells. Here, we present a strategy to overcome this dilemma. We mimic the hierarchical structure of tissues using protein-based hydrogels such as gelatin. This structure leads to the combination of soft tissue-like mechanical properties, uniform 3D cellularization, and great bioactivity.