Molecular Engineering of Recombinant Protein Hydrogels: Programmable Design and Biomedical Applications

Recombinant protein hydrogels represent a significant advancement in biomaterials, offering solutions to the limitations of traditional synthetic systems by mimicking extracellular matrix dynamics through genetically engineered backbones. These hydrogels are constructed using a hierarchical crosslinking strategy that combines reversible physical interactions with covalent crosslinking, providing mechanical strength, environmental responsiveness, and controlled degradation. Molecular engineering is crucial for precise functionality, utilizing domain-directed self-assembly and modular fusion of bioactive motifs to control cellular interactions and therapeutic release. These engineered hydrogels have advanced applications in areas such as diabetic wound regeneration, tumor-responsive drug delivery, and bioprinting. The review highlights the integration of synthetic biology and materials science to create adaptive biomaterials for regenerative medicine and other complex challenges.