Intelligent Metal-Phenolic Metallogels as Dressings for Infected Wounds

In this study, we report a metallogel developed based on metal-phenolic coordination of natural low-cost polyphenolic molecule and metal ions. Gelation occurs by mixing tannic acid (TA) and group (IV) titanium ions (Ti^IV) to form TA-Ti^IV gel. The TA-Ti^IV gel exhibits good capability to incorporate diverse metal ions by in situ co-gelation. Herein, five antimicrobial metal ions, i.e. ferric (Fe^III), copper (Cu^II), zinc (Zn^II), cobalt (Co^II) and nickel (Ni^II) ions, were employed to include in TA-Ti^IV gels for developing intelligent dressings for infected wounds. The chemical and coordinative structures of TA-Ti^IV metallogels were characterized by UV-Vis and Fourier-transform infrared (FT-IR) spectroscopies. Cytotoxicity of antimicrobial metallogels was explored by MTT assay with NIH 3T3 fibroblasts. The release of metal ions was evaluated by inductively coupled plasma mass spectrometry (ICP-MS), indicating the different releasing profiles upon the coordinative interactions of metal ions with TA. The formation and disassembly of metallogels are sensitive to the presence of acid and an oxidizer, H₂O₂, which are substances spontaneously generated in infected wounds due to the metabolic activity of bacteria and the intrinsic immune response. The Cu^II releasing rates of TA-Ti^IV-Cu^II metallogels at different pH values of 5.5, 7.4 and 8.5 have been studied. In addition, addition of H₂O₂ trigger fast release of Cu^II as a result of oxidation of galloyl groups in TA. Consequently, the antimicrobial potency of TA-Ti^IV-Cu^II metallogels can be simultaneously activated while the wounds are infected and healing. The antimicrobial property of metallogels against Gram-negative Escherichia coli, and Gram-positive Methicillin-Resistant Staphylococcus aureus (USA300) and Staphylococcus epidermidis has been investigated by agar diffusion test. In an animal model, the TA-Ti^IV-Cu^II metallogels were applied as dressings for infected wounds, indicating faster recovery in the wound area and extremely lower amount of bacteria around the wounds, compared to TA-Ti^IV gels and gauze. Accordingly, the intelligent nature derived metallogels is a promising and potential materials for medical applications.