Conserved Sequence-Derived from Keratins Guides Design of Self-Assembling Protein for Accelerated Wound Healing

Despite considerable subtype diversity among the 17 human hair keratins, all keratin subtypes exhibit remarkable capabilities in promoting clotting, facilitating wound healing, and undergoing self-assembly. However, their conserved bioactive motifs remain unclear. Here, we identified specific conserved motifs derived from highly conserved regions of type I and type II human hair keratins, which were used to design a keratin-mimetic protein named KRTn4 by incorporating four repeats of these conserved keratin motifs. This novel design strategy enables KRTn4 to undergo more efficient self-assembly compared to traditional keratins. More importantly, KRTn4 is capable of both homotypic and spherical assembly. Additionally, the self-assembling hydrogel exhibits enhanced structural integrity and significantly improved cell-regulatory activity. Notably, the KRTn4 hydrogel facilitates superior in vivo hemostatic efficiency and wound healing performance. These results establish KRTn4 as a bioinspired, self-assembling hydrogel with potent regenerative properties, offering a promising new approach for advanced wound healing applications.