Regulatable and reversible native paramyosin hydrogels promote the wound healing of the skin in mice

Protein hydrogels with multifunction including tunable mechanical property, sustained drug release and excellent biocompatibility have shown considerable promise in biological applications. However, these hydrogels are usually generated using denatured or modified protein molecules, it remains challenging to construct injectable hydrogel based on native protein as building blocks. Here, a native nanofibrous protein, paramyosin (PM) was utilized as building blocks to create hydrogels under mild conditions, taking advantage of Zn2+-mediated metal coordination with His-Glu motifs located on the exterior surface of the protein. The bioactive substance cyanidin-3-O-galactoside was shielded from light-induced degradation by being enclosed in the native PM hydrogels. Moreover, the rheological property and biological activity of construction PM hydrogels were improved through noncovalent interactions with natural polyphenols, such as proanthocyanidins. Importantly, all of these manufactured native hydrogels endow good biocompatibility, reversible sol–gel transforming behavior, great stability, and considerably speed up the healing of wounds in mice with skin injuries. Overall, these hydrogels derived from natural protein not only demonstrates beneficial qualities that are very effective in encouraging wound healing, but also offers a straightforward and repeatable gelation approach to produce protein hydrogel employed in biomedical applications.