Recent advances in protein hydrogels: From design, structural and functional regulations to healthcare applications

Protein hydrogels with three-dimensional network structure can be synthesized through both covalent and noncovalent cross-linking of protein monomers and assemblies, which have shown wide applications in various fields due to their low toxicity, higher biocompatibility, better bioactivity, and better flexibility compared to traditional inorganic and polymeric hydrogels. In this review, we present recent advances (2016 to current) in the synthesis, structural and functional regulation, as well as healthcare applications of protein hydrogels. We provide detailed information on the synthesis of protein hydrogels via chemical, physical, and biological stimulations, and then introduce their unique self-healing, stimuli-responsive, swelling, mechanical, biological, and injectable properties. Furthermore, we analyze the strategies that can be utilized to regulate the structures and functions of protein hydrogels through tailoring the coiled-coil, porous, and periodic structure, as well as adding various functional materials into protein hydrogels. Finally, the healthcare applications of protein-based hydrogels for wearable devices, biosensors, drug/gene delivery, disease treatment, tissue engineering, cancer therapy, and bioimaging are demonstrated and discussed. It is the first effort to demonstrate excellent contributions of protein hydrogels to healthcare fields, which will be valuable for the readers to design and synthesize functional bio-hydrogels rationally and further to develop novel hydrogels for advanced applications.