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, H(2)O(2), 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 H(2)O(2) 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.