Dual Drug-Loaded Hyaluronate-Based Self-Adaptable Hydrogel for Diabetic Infected Wound Healing

Diabetic infected wounds struggle to self-heal due to hyperglycemia, bacterial infection, and lack of effective treatments. Herein, a hyaluronic-based self-adaptable (HASA) hydrogel was developed via the host-guest interaction between γ-cyclodextrin (γCD) and coumarin. The reversible host-guest linkers conferred the HASA hydrogel with high network dynamics, enabling excellent injectability and shape adaptability. By encapsulating the levofloxacin (LEV) within the γCD cavity and incorporating the insulin (INS) into the hydrogel network, a dual drug-loaded HASA (HASA@LEV&INS) hydrogel was easily fabricated. Owing to its efficient enzymatic degradation and drug release properties, the HASA@LEV&INS hydrogel showed remarkable abilities in inhibiting bacterial growth and upregulating cell activity under high-glucose conditions. In treating diabetic infected wounds, the HASA@LEV&INS hydrogel achieved a wound contraction rate of up to 96.8% by day 14, demonstrating enhanced wound healing efficacy. This work provides a promising strategy for accelerating the healing of diabetic infected wounds.