Intelligent Metal-Phenolic Metallogels as Dressings for Infected Wounds

Abstract

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.

Bacterial Nanocellulose-Enhanced Alginate Double-Network Hydrogels Cross-Linked with Six Metal Cations for Antibacterial Wound Dressing

“…BNC/Alg-Co and BNC/Alg-Ag showed remarkable inhibition on bacterial growth for both Gram-positive and Gram-negative bacteria. This result is in accordance with the literature reporting that the antimicrobial activity of cobalt is higher than copper, followed by zinc [ 4 ]. It has been reported cerium ion is unable to penetrate mammalian cell membranes, but it has a noticeable antibacterial activity even at lower concentrations [ 8 , 43 ].…”

“…The release of cations was characterized and recorded for 48 h using an inductively coupled plasma-mass spectrometer (ICP-MS, Agilent 7500ce, Tokyo, Japan) [ 4 ]. The synthesized dressings were cut into round discs with a diameter of 3 cm.…”

“…In a fast and efficient healing process preventing infection is a critical concern that can begin with germy obstruction when changing the wound dressing [ 3 ]. Infection can lead to pain, deep tissue and bone inflammation, chronic wounds, tenderness, cellulitis, abscess, blood poisoning, and even death [ 4 ]. Development of novel strategies for the treatment of infected wounds is imperative, and has been highlighted by the World Health Organization (WHO) for several years [ 5 ].…”

“…Up to now, many antibacterial wound dressings have been developed using different antibacterial agents, but the ability to release more antibacterial agents in the area with lower pH value (an indicator of infected wounds) is a critical concept of functional wound dressing [ 16 , 17 ]. As it is widely reported that pH of infected wound falls to around 5.5 [ 4 ], it is expected that the dressing materials could be used as smart dressings due to the possible higher release of cations at lower pH to achieve stronger antibacterial activity. Higher level of cation release can be the result of Alg deformation or shrinkage at lower pH [ 18 ].…”

Biological Activity of New Cichoric Acid–Metal Complexes in Bacterial Strains, Yeast-Like Fungi, and Human Cell Cultures In Vitro

“…In our research we proposed determining the antimicrobial properties of one from polyphenol acids, cichoric acid, in combination with metals such as Co, Cu, Ni, and Zn. Antimicrobial and antifungal properties of metal ions have been known and explored for many years [36]. The antimicrobial activity of the metal ions is linked with the cell membrane destabilization and disruption of the bacterial membrane permeability.…”