Introduction: The management of diabetic chronic wounds remains a significant global challenge due to exacerbated inflammatory responses, oxidative stress, and persistent infections during the healing process. Reactive oxygen species (ROS) are released too much in diabetic wounds, which causes intense inflammatory reactions as well as lipid peroxidation, protein denaturation, and malfunctioning of endogenous stem cells and macrophages, all of which slow down wound healing. There exists a critical need for wound dressing materials that exhibit optimal biocompatibility, sufficient mechanical strength, robust underwater adhesion, and effective anti-inflammatory, antioxidant, and antibacterial properties for clinical applications. Hydrogels have garnered considerable attention as wound dressings for diabetic wound healing due to their three-dimensional porous networks and appropriate swelling characteristics. These materials demonstrate the capacity to absorb wound exudates, maintain a moist environment, and serve as delivery systems for bio-functional components or cells to promote healing. Recent advancements have focused on hydrogels incorporating naturally extracted substances, owing to their exceptional biocompatibility and biosafety. Tannic acid (TA), a natural plant polyphenol, has demonstrated promising antimicrobial, anti-inflammatory, antioxidant, and hemostatic properties. TA can form physical crosslinks with hydrogels through multiple hydrogen bonds and hydrophobic interactions under neutral conditions. Its 25 phenolic hydroxyl groups enable TA to crosslink hydrophilic macromolecules, facilitating the formation of a hydrogel network. Various materials, including natural polysaccharides and synthetic polymers such as chitosan, alginate, cellulose, and hyaluronic acid, are being utilized to fabricate advanced biological macromolecule-based hydrogels. These materials are frequently enriched with antibacterial and antioxidant agents to impart multifunctional attributes for wound healing purposes. This review aims to examine recent research progress on the application of Tannic acid as an antibacterial, antioxidant, and anti-inflammatory agent in multifunctional hydrogels for the treatment of diabetic wounds.
Methods: Two methods are described for preparing a hydrogel dressing containing tannic acid:
1. Post-fabrication immersion method:
- Prepare the hydrogel from the desired polymer solution
- Dissolve varying concentrations of tannic acid in deionized water
- Immerse the prepared hydrogel dressing in the tannic acid solution for 24 hours
2. Direct incorporation method:
- Dissolve tannic acid powder directly into the polymer solution at the desired concentration
- Prepare the hydrogel containing tannic acid in a single step
The choice between these methods depends on factors such as the desired tannic acid distribution, production scale, time constraints, and the specific properties required for the final hydrogel dressing.
Results: In vitro and in vivo investigations have shown that the polyphenol groups of TA in multifunctional hydrogels hastened the healing of skin incisions and defects by modulating inflammation, promoting collagen deposition, and vascularization. TA may decrease nuclear factor-κB translocation and reduce inflammatory cytokines, resulting in an anti-inflammatory effect. E. coli and S. aureus growth were effectively suppressed, and antioxidant activity was outstanding. Furthermore, the hydrogels generated by crosslinking TA with a polymer matrix had improved mechanical characteristics. Notably, in vivo studies showed that the hydrogel enhanced diabetic wound healing by activating M2 polarization, anti-inflammation, and pro-angiogenesis.
Conclusion: Several factors contribute to the healing of diabetic wounds, including antibacterial and antioxidant effects, enhanced angiogenesis, and oxygen generation. To mitigate the deleterious impact of bacterial infections on wound recovery, it is imperative to develop novel hydrogel-based dressings that possess both antibacterial and anti-inflammatory properties. Consequently, there is an urgent need for the identification of new non-antibiotic agents that combat bacteria, to reduce antibiotic usage and prevent the emergence of antibiotic-resistant strains. As a result, multifunctional hydrogels are anticipated to be extensively utilized in the clinical management of diabetic wounds.