Genetically encoded zinc-binding collagen-like protein hybrid hydrogels for wound repair

Abstract

Incorporating zinc oxide nanoparticles (ZnOnps) into collagen is a promising strategy for fabricating biomaterials with excellent antibacterial activity, but modifications are necessary due to the low zinc binding affinity of native collagen, which can cause disturbances to the functions of both ZnOnps and collagen and result in heterogeneous effects. To address this issue, we have developed a genetically encoded zinc-binding collagen-like protein, Zn-eCLP3, which was genetically modified by Scl2 collagen-like protein. Our study found that Zn-eCLP3 has a binding affinity for zinc that is 3-fold higher than that of commercialized type I collagen, as determined by isothermal titration calorimetry (ITC). Using ZnOnps-coordinated Zn-eCLP3 protein and xanthan gum, we prepared a hydrogel that showed significantly stronger antibacterial activity compared to a collagen hydrogel prepared in the same manner. In vitro cytocompatibility tests were conducted to assess the potential of the Zn-eCLP3 hydrogel for wound repair applications. In vivo experiments, which involved an S. aureus-infected mouse trauma model, showed that the application of the Zn-eCLP3 hydrogel resulted in rapid wound regeneration and increased expression of collagen-1α and cytokeratin-14. Our study highlights the potential of Zn-eCLP3 and the hybrid hydrogel for further studies and applications in wound repair.