One-step photochemical crosslinking of native proteins is feasible in tyrosine-rich bovine serum albumin

Hydrogels made by crosslinking biomolecules have wide-ranging applications, including pharmaceuticals and tissue engineering. Some research groups have demonstrated crosslinking polycarbonates or oligopeptides by first attaching a tyrosine crosslinker to the backbones and then initiating crosslinking among linkers. Herein, we explored an alternative approach to make hydrogels from native proteins without pre-modification. We hypothesized that it is feasible to photochemically crosslink unmodified proteins provided that the protein is naturally abundant in tyrosine groups. We chose bovine serum albumin (BSA, a protein containing 18 tyrosine residues) as the native protein and methylene blue (MB) as the photosensitizer. To test our hypothesis, we photo-illuminated a solution of BSA and MB and observed whether a hydrogel formed. After illumination, the solution became a gel-like film whereas the solution not subject to illumination remained fluidic, indicating that photochemically crosslinking unmodified proteins is feasible. Using a microscope objective lens to focus the laser beam and a stage to move the sample, we further demonstrated photo-printing finely structured hydrogels. To illustrate a potential application of the hydrogels, we showed that the structured hydrogels can incorporate a model drug (fluorescein), and can be transferred and adhered to a model skin (pig skin), acting like a liquid bandage. In conclusion, we verified the feasibility of making hydrogels from a native protein naturally rich in tyrosine without the extra step of introducing crosslinkers to the protein backbone and demonstrated photo-printing fine structures of protein hydrogels. More work will be necessary to explore novel applications of protein hydrogels.