Significance: Photoresponsive hydrogels have lately received ample attention because of their great potential in biomedical applications. However, the use of an entirely recombinant protein-based hydrogel with light-sensing abilities for stem cell applications has rarely been shown. Here, we created a B ₁₂ -dependent light-sensing hydrogel by covalently stitching together the photoreceptor C-terminal adenosylcobalamin binding domain (CarH _C ) proteins under mild conditions. The polymeric CarH _C proteins self-assemble into an elastic hydrogel in the presence of adenosylcobalamin in the dark and disassemble rapidly on light exposure. Such a photoresponsive protein hydrogel system enabled facile release/recovery of stem cells and protein molecules. This direct assembly of stimuli-responsive proteins into hydrogels represents a versatile strategy for designing “smart” materials and opens up enormous opportunities for future material biology.

Axon regeneration constitutes a fundamental challenge for regenerative neurobiology, which necessitates the use of tailor-made biomaterials for controllable delivery of cells and biomolecules. An increasingly popular approach for creating these materials is to directly assemble engineered proteins into high-order structures, a process that often relies on sophisticated protein chemistry. Here, we present a simple approach for creating injectable, photoresponsive hydrogels via metal-directed assembly of His6-tagged proteins. The B₁₂-dependent photoreceptor protein CarH_C can complex with transition metal ions through an amino-terminal His6-tag, which can further undergo a sol-gel transition upon addition of AdoB₁₂, leading to the formation of hydrogels with marked injectability and photodegradability. The inducible phase transitions further enabled facile encapsulation and release of cells and proteins. Injecting the Zn²⁺-coordinated gels decorated with leukemia inhibitory factor into injured mouse optic nerves led to prolonged cellular signaling and enhanced axon regeneration. This study illustrates a powerful strategy for designing injectable biomaterials.

This review highlights the recent development and future opportunities in the interdisciplinary field, integrating microfluidic technology and microbial engineering.