Anti-inflammatory and antibacterial hydrogel based on a polymerizable ionic liquid

In the present era, the treatment of skin-infected wounds and their associated inflammation constitutes a significant challenge. These infections have the potential to impede the healing process and become a life-threatening pathology, particularly due to the rise of bacterial resistance. Hydrogels could successfully address this issue due to their unique capabilities and versatility. Among them, natural polymer-based hydrogels are especially advantageous as they resemble the extracellular matrix (ECM) and mechanical properties of natural tissues. In this study, we propose a dual-action hydrogel composed of methacrylated gelatin as a matrix and a salicylate (Sal) anion-exchanged polymerizable ionic liquid (PIL) to achieve anti-inflammatory and antibacterial activities. This material facilitated cell attachment and colonization with mouse endothelial fibroblasts. A flow cytometry assay was conducted to evaluate the anti-inflammatory effect, and demonstrated the differentiation of mouse macrophages to an M2 (reparative) phenotype. Therefore, the levels of TNF-α, interleukin-6 (IL-6), and interleukin (IL-10) were quantified to further evaluate this effect, demonstrating an inhibition on the pro-inflammatory ones. The inherent antibacterial capacity of the PIL was demonstrated against Staphylococcus aureus and Escherichia coli, thereby corroborating its potential as a wound dressing. To the best of our knowledge, this is the first reported hydrogel incorporating an anion-exchanged polymerizable ionic liquid that is capable of promoting macrophage differentiation into a reparative phenotype, of reducing pro-inflammatory cytokines, and of simultaneously retaining antibacterial activity. These features open the gate to the potential application of this hydrogel as a wound dressing. STATEMENT OF SIGNIFICANCE: Bacterial wound infections may lead to severe problems due to their associate tissue inflammation and the emergence of bacterial resistance. In this sense, local therapies such as hydrogels have gathered much attention as alternative therapies for these pathologies. In this work, we have developed a natural polymer-based hydrogel copolymerized with a polymerizable ionic liquid containing salicylate as an anion. The hydrogel was shown to be biocompatible, and promoted macrophage differentiation to a reparative phenotype, while reducing the levels of pro-inflammatory cytokines. Finally, the high antibacterial capability against both gram-positive and gram-negative bacteria makes it a promising candidate for use in wound dressings.