Immunomodulatory, Antibacterial, Antioxidative and EGF‐Delivering Hydrogel Remodels Wound Microenvironment for Infected Diabetic Wound Healing

Abstract

ABSTRACT The treatment of diabetic wounds remains a major challenge due to persistent bacterial infections, chronic inflammation, and impaired angiogenesis. To address these issues, we develop an immunomodulatory and antibacterial hydrogel integrating epidermal growth factor (EGF)‐loaded liposomes for efficiently accelerating diabetic wound healing. The hydrogel is formed through the crosslinking reaction between gallic acid‐modified ε‐poly‐L‐lysine (ε‐PLL‐GA) and o ‐phthalaldehyde‐functionalized four‐arm polyethylene glycol (4aPEG‐OPA). The hydrogel exhibits robust broad‐spectrum antimicrobial properties, and achieves a bacterial inhibition rate of 99.9% in a subcutaneous infection model. The hydrogel exhibits prominent antioxidative and reactive oxygen species (ROS) scavenging properties, and demonstrates immunomodulatory M2‐inducing effects on macrophages. Moreover, sustained release of EGF from the liposome‐incorporated hydrogel system promotes cell migration and tube formation of human umbilical vein endothelial cells. The immunomodulatory, antibacterial and EGF‐releasing hydrogel demonstrates remarkably improved wound healing efficacy in both diabetic foot ulcer and bacteria‐infected diabetic wound models by remodeling the wound microenvironment. These findings present strong potential of the multifunctional hydrogel for the effective treatment of complicated chronic wounds such as diabetic wounds and infected wounds.