Thiosemicarbazones-Loaded Injectable Hydrogels with Self-Healing and Antibacterial Activity for Wound Healing

Abstract

An injectable hydrogel loading α-N-heterocyclic thiosemicarbazones with antibacterial activity was designed to attain therapy against wounds with high efficiency. In the present study, the injectable FPZ-H₂L hydrogel was synthesized by loading 2,6-diacetylpyridine bis(N⁴-methylthiosemicarbazone) (H₂L) on transition-metal ions (Zn²⁺)-cross-linked-folic acid (FA)-co-polydopamine (PDA) hydrogel (FPZ hydrogel). The injectable hydrogel (FPZ-H₂L) cross-linked by coordination and hydrogen bonds displayed an excellent self-healing performance and completely covered the irregular wound. Compared with the FPZ hydrogel, the FPZ-H₂L hydrogel has stronger antibacterial efficacy on typical Gram-positive/negative bacteria and drug-resistant bacteria. The antibacterial mechanisms of the hydrogel were related to biofilm ablation, the disruption of the cell membrane integrity, leakage of nucleic acids and proteins, and the production of oxidative stress response, thus causing bacterial death. Cell Counting Kit-8 (CCK-8) test shows that FPZ-H₂L hydrogel has excellent cell compatibility, and gel drug loading technology greatly overcomes the problem of high cytotoxicity of H₂L. The wound healing experiments indicated that the hydrogel enhanced the wound healing efficacy of mice. These results prove that the mixed hydrogel has broadened the field of vision for the design of antibacterial wound dressings.