Ruthenium Dioxide-Incorporated Dual-Responsive Hydrogel Promotes MRSA-Infected Diabetic Wound Healing via Microenvironment Remodeling.

Severe microenvironmental imbalance in diabetic wounds infected with drug-resistant bacteria, a clinically prevalent issue yet often overlooked as a distinct pathological entity, results in a lack of coordinated multidimensional regulation of the wound microenvironment, which remains largely underexplored in current studies. Herein, we report a pH/ROS-responsive multifunctional hydrogel (G@Ru) incorporating RuNPs. G@Ru is constructed via dynamic Schiff base and boronate ester linkages, which endow it with dual stimulus responsiveness, injectability, adhesiveness, self-healing, and hemostatic properties. In addition, the intrinsic antibacterial activity of RuNPs enables the inhibition of methicillin-resistant Staphylococcus aureus. Furthermore, in vivo studies confirm that G@Ru can regulate macrophage polarization, modulate reactive oxygen species levels, enhance cell proliferation, stimulate angiogenesis, and accelerate tissue regeneration, thereby reshaping the wound microenvironment in a multidimensional manner. Ultimately, G@Ru exhibits superior therapeutic efficacy, achieving a wound closure rate of 98% in infected diabetic wounds by day 14, highlighting its antibiotic-free therapeutic potential and promising clinical translational applications.