## 4 Polyphenol-Based Systems and Their Unveiling Potential for Wound Care
### Antimicrobial Polyphenol Wound Dressings  
Given the antimicrobial and antioxidant potential of polyphenols, it is believed that phenolic compounds can be great bioactive agents to be incorporated in wound dressings for chronic wound treatment, playing a key role in wound care. There are already some studies that validate the use of polyphenols with antioxidant or/and antimicrobial properties to promote wound healing (Table 1). Thymol, a polyphenol, was incorporated into different wound dressings, such as films and hydrogels, due to the antioxidant and antimicrobial potential of the phenolic compound, revealing great results as a wound healing promoter [60]. Along the same lines, kaempfer, chlorogenic acid, resveratrol, and ferulic acid are some examples of phenolic compounds with great antioxidant properties to promote wound healing in chronic wounds. Tannic acid is a tannin with interesting properties, such as antioxidant, antiviral, hemostatic, anti-inflammatory, anticarcinogenic, and antimicrobial activities. The use of tannic acid as a bioactive compound for the treatment of wounds and skin ulcers has already been proved. [PERSON] et al. [61] prepared an antioxidant and antimicrobial hydrogel composed of free tannic acid by using trimethylol-propane triglyceride ether as a cross-linker for chronic wound application. This study was the first and only one related to a fully polyphenic hydrogel to be used as wound healing for chronic wounds. Through minimum inhibition concentration values, the wound dressing displayed antimicrobial activity against _P. aeruginosa_, _S. aureus_, _Bacillus subtilis_, and _Candida albicans_. In another study, antibacterial tannic acid metallogels were developed as infected wound dressings with responsive properties. The metallogels were synthesized via co-gelation of tannic acid, high-oxidation state titanium ions (TiIVs), and antimicrobial metal ions for the formation of three-dimensional metal-phenolic networks (MPNs) [62]. The antimicrobial metal ions of ZnII, CoII, NiII, FeIII, and CuII were included in the metallogels to evaluate the release profiles, cytotoxicity, and antimicrobial potency. The best results were achieved for TA-TiIV-CuII metallogels as antimicrobial dressing, indicating healing in the wound area and the infection control, compared to TA-TiIV gels and gauze. The smart formulation was revealed to be a promising and potential material for medical applications. [PERSON] et al. [63] also anchored tannic acid/Ca (II) on the surface of chitin nanofiber sponge by layer-by-layer deposition based on the coordination complex of tannic acid and Ca\({}^{2+}\). The results revealed that these chitin nanofiber sponges anchored TA/Ca (II) coating had rapid hemostatic and antibacterial properties, which may have great potential to design hemostatic products in biomedical application. In a different perspective, [PERSON] et al. [64] developed biocompatible tannic acid (TA)/chitosan (CS)/pullulan (PL) composite nanofibers (NFs) with synergistic antibacterial activity against _E. coli_. The NFs were developed utilizing the forcespinning(FS) technique from CS-CA aqueous solutions to avoid the usage of toxic organic solvents. These new NFs favored the fixation and growth of fibroblasts, providing a 3D environment that promises to imitate the extracellular matrix (ECM) in the skin. They were also capable of allowing cells to move through the fibrous structure, enhancing interlayer growth across the membrane and the consequent deep and intricate wound healing. In terms of healing properties of the polyphenol, a very recent study evaluated wound healing properties of free tannic acid by in vitro and in vivo tests, and results revealed that the tannin was able to accelerate re-epithelial and increase hair follicles [65]. Thus, once the healing properties of tannic acid are known, it is expected to have great potential in its incorporation into biomaterials for wound care as a natural antimicrobial and antioxidant agent for chronic wounds [64].