The synergistic effect of a ruthenium complex-sodium alginate hydrogel on biofilm eradication and wound healing acceleration

The rapid emergence of antibiotic resistance and resilient bacterial biofilms poses a critical threat to global public health. To address this challenge, we developed SA-GDL-Ru—a novel sodium alginate hydrogel integrated with a synthesized ruthenium(II) complex ( Ru , RuCl(η⁶-C₆H₆)(TolBig)). This hydrogel overcomes the poor aqueous solubility and toxicity limitations of traditional metal complexes while enhancing antibacterial efficacy. In vitro studies demonstrated potent activity against Staphylococcus aureus (MIC = 13.90 μM) and Escherichia coli (MIC = 20.85 μM), with the SA-GDL-Ru hydrogel (SGR-2) exhibiting 6–8-fold greater reactive oxygen species (ROS) induction than Ru alone. Transcriptomic analysis revealed that SA-GDL-Ru downregulates fabH (fatty acid synthase) and sigB (biofilm synthesis) genes while upregulating quorum-sensing regulators (agrA/agrC), disrupting biofilm integrity. Molecular docking confirmed Ru ’s binding affinity with biofilm-associated proteins, inhibiting key enzymatic functions. Crucially, SA-GDL-Ru accelerated wound closure in S. aureus -infected mice by 4 days through EGFR/Akt pathway activation, increasing VEGF-A/HIF-1α and reducing Caspase-3 expression. In acute pneumonia models, it achieved near-complete bacterial eradication with suppressed inflammation. Safety assessments confirmed minimal cytotoxicity (< 25 μM in zebrafish) and no hemolysis or organ damage. This work establishes SA-GDL-Ru as a translatable therapeutic platform combating biofilm-mediated infections while promoting tissue regeneration.