Self‐Gelling Powder Integrated with Multienzyme‐Like Nanozyme for the Management of Infected Diabetic Wounds

Bacterial infection, hindered vascularization, excessive reactive oxygen species (ROS), and persistent inflammation are the intricate problems that delay infected diabetic wound repair. Herein, we constructed an in-situ sprayed self-gelling powder system (Vc-Cu@CP) that is composed of carboxymethylcellulose sodium (CMC-Na)/ε-polylysine (ε-PL) hydrogel (CP) and L-Ascorbic acid-stabilized multifunctional copper nanozymes (Vc-Cu), with functions of exudate absorption and antibacterial for bacterial-stained wound healing. Research demonstrated that an early acidic microenvironment with excessive ROS can activate POD-mimic enzyme activity of Vc-Cu nanozymes to kill bacteria through chemodynamic therapy. Furthermore, the microenvironment of chronic wounds triggers the SOD/CAT-mimic cascade catalytic reaction of Vc-Cu nanozymes, effectively scavenging ROS while providing oxygen. In vitro/in vivo studies revealed that the composite powder can quickly absorb wound exudate and transform into a hydrogel through intermolecular hydrogen bonds or electrostatic effects, facilitating the formation of a physical barrier and achieving in situ infected diabetic wound care. Additionally, RNA-seq results illustrated that the self-gelling powder upregulated genes related to wound healing and downregulated multiple signaling pathways related to inflammation and immune response, synergistically accelerating collagen deposition, angiogenesis, and epithelial regeneration. This study highlights the self-gelling powder system (Vc-Cu@CP) as a promising candidate for the management of complicated diabetic wounds.