Genetically Programmed Single‐Component Protein Hydrogel for Spinal Cord Injury Repair

Abstract Protein self‐assembly allows for the formation of diverse supramolecular materials from relatively simple building blocks. In this study, a single‐component self‐assembling hydrogel is developed using the recombinant protein CsgA, and its successful application for spinal cord injury repair is demonstrated. Gelation is achieved by the physical entanglement of CsgA nanofibrils, resulting in a self‐supporting hydrogel at low concentrations (≥5 mg mL −1 ). By leveraging the programmability of the CsgA gene sequence, the bioactive hydrogel is enhanced by fusing functional peptide GHK. GHK is recognized for its anti‐inflammatory, antioxidant, and neurotrophic factor‐stimulating properties, making it a valuable addition to the hydrogel for spinal cord injury repair applications. In vitro experiments demonstrate that the CsgA‐GHK hydrogel can modulate microglial M2 polarization, promote neuronal differentiation of neural stem cells, and inhibit astrocyte differentiation. Additionally, the hydrogel shows efficacy in alleviating inflammation and promotes neuronal regeneration at the injury site, leading to significant functional recovery in a rat model with compression injury spinal cord cavity. These findings lay the groundwork for developing a modular design platform for recombinant CsgA protein hydrogels in tissue repair applications.