Multifunctional Quercetin-Loaded TiO2@CNTs/Chitosan Hydrogels for Synergistic Antibacterial Therapy and Accelerated Wound Healing

Chronic wound management requires multifunctional biomaterials integrating antibacterial and tissue-repair capacities. To address this clinical demand, we developed a composite hydrogel by incorporating quercetin-loaded TiO 2 @CNTs heterojunctions into chitosan, leveraging their complementary properties: chitosan's excellent biocompatibility as the matrix, quercetin's natural anti-inflammatory effects, TiO 2 ’s photocatalytic antibacterial activity, and CNTs’ structural reinforcement. The TiO 2 @CNTs heterojunction was synthesized hydrothermally, with characterization confirming uniform TiO 2 dispersion on CNTs, anatase-phase crystallinity, and robust interfacial bonding. The composite hydrogel showed thermoresponsive gelation at 37 °C, favorable porcine skin adhesion, and a porous microstructure. In vitro tests revealed >90% L929 fibroblast viability (25 µM quercetin optimal), enhanced cell migration, and hemolysis rates <5%. Antibacterial assays against Escherichia coli demonstrated significantly larger inhibition zones (18.2 ± 1.3 mm) and lower bacterial counts for the composite hydrogel than those for the chitosan-only or control groups. In a rat skin wound model, the hydrogel achieved 60% wound closure at 7 days, outperforming the chitosan (50%) and control (40%) groups. Furthermore, histological and blood biochemical analyses confirmed no systemic toxicity, organ damage, or TiO 2 /CNT accumulation in major organs. This multifunctional hydrogel exhibits synergistic antibacterial, biocompatible, and pro-healing properties, making it a promising candidate for advanced chronic wound care applications.