Multifunctional Polyrotaxane Hydrogel with Dynamic Molecular Anchors and Microenvironment-Activatable Cationization Properties for Healing Drug-Resistant Bacterial-Infected Chronic Skin Wounds

The wound healing process in diabetic patients is often complex and prolonged, frequently complicated by persistent bacterial infections that can develop into multidrug-resistant infections, posing significant challenges for treatment. However, traditional hydrogel dressings often exhibit limited efficacy against complex wounds, primarily because therapeutic molecules are confined within the cross-linked matrix and exert nonselective antibacterial effects. This study developed a novel polyrotaxane-based hydrogel (FDS) against diabetic wounds complicated by drug-resistant bacterial infections. By assembling SNO-modified β-cyclodextrin onto the F-127DA copolymer backbone and copolymerized with dimethylamino propyl methacrylamide (DMAPMA), FDS hydrogel was endowed with conformational freedom of NO (Nitric Oxide) donor through rotatable and slidable motions and acid-responsive antibacterial properties simultaneously. This FDS hydrogel exhibited excellent antibacterial (both <i>Staphylococcus aureus</i> and methicillin-resistant <i>S. aureus</i>) and biofilm-dispersing effects, NO-enhanced angiogenesis, significantly reduced inflammatory response, and accelerated healing of chronic diabetic wounds <i>in vitro</i> and <i>in vivo</i>. By virtue of movable molecular anchoring facilitated NO delivery and microenvironment-activatable antibacterial activity, this research offers new hope for addressing the challenges of wound healing in diabetic patients accompanied by bacterial infections.