Designing Halogen-free Metal-phenolic Imidazolium Poly(Ionic Liquids) with Muti-functional Antibacterial, Anti-inflammatory and Cell Proliferation Properties for Infected Wounds

Abstract

Infected wounds are challenging to heal because they are complicated by bacterial infections, persistent inflammation, and impaired cell proliferation. Recently, imidazolium poly(ionic liquids) (PILs) as high effective antibacterial agent has been developed in infected wound healing. However, traditional imidazolium-based PILs containing halogen groups have shown potential cytotoxicity. In this study, we designed halogen-free metal-phenolic imidazolium PILs (HMPIPs) with antibacterial, anti-inflammatory and cell proliferation. Firstly, poly(vinyl-butylimidazolium dihydroxyphenylpropionic acid) (PVD), was synthesized via radical polymerization, anion exchange, and catechol deprotection. Subsequently, the HMPIPs were individually coordinated with metals ions (Zn²⁺, Mg²⁺, Cu²⁺, Fe³⁺). The results indicated that PVD@Zn could form stable MPIP microparticles. In vitro assays revealed that PVD@Zn exhibited potent antibacterial activity against Escherichia coli (MIC: 512 μg/mL) and Staphylococcus aureus (MIC: 128 μg/mL), likely due to the synergistic effects of the imidazolium group’s positive charge. Additionally, PVD@Zn exhibited anti-inflammatory effects by suppressing reactive oxygen species (ROS) and nitric oxide (NO) levels, and downregulating TNF-α, IL-1β, IL-6, and iNOS through Zn²⁺-mediated regulation. Notably, it enhanced L929 fibroblast proliferation by 22% via upregulation of amino acid biosynthesis pathways. In vivo assays further demonstrated that PVD@Zn significantly accelerated wound closure (97% contraction within 11 days), effectively reduced bacterial load (93% eradication), and exhibited minimal systemic organ toxicity. The multifunctional HPIPs, PVD@Zn, demonstrated antibacterial, anti-inflammatory, and pro-proliferative properties, potentially reducing the risk of drug overuse during wound healing. This system holds promise for future clinical application as an encapsulated therapeutic agent.