Multifunctional ADM hydrogel containing endothelial cell-exosomes for diabetic wound healing

Non-healing trauma, with limited treatment options, remains a prevalent complication of diabetes mellitus. The underlying causes wherein include oxidative stress injury, bacterial infection, cellular dysfunction, and persistent inflammation. Acellular Dermal Matrix (ADM), a wound dressing composed of natural extracellular matrix and abundant bioactive factors, has been successfully developed to treat various wounds, including burns and diabetic ulcers. Protocatechualdehyde (PA) & trivalent iron ion (Fe3+) complex (Fe3+@PA) exhibits potential antioxidant and antibacterial properties. In this study, we developed a dual hydrogel network by combining Fe3+@PA complex-modified ADM with light-cured gelatin (GelMA), supplemented with exosomes derived from umbilical vein endothelial cells (HUVECs-Exos), to create an ADM composite hydrogel system (ADM-Fe3+@PA-Exos/GelMA) with antioxidant, antibacterial, and cell-promoting functions for diabetic wound treatment. Through in vitro experiments, we firstly investigated the biosafety, antioxidant and antibacterial properties of ADM composite hydrogel. Furthermore, we examined the protective effects of the hydrogel on cellular function in a diabetic model. In animal experiments, we comprehensively evaluated the therapeutic effects of the ADM composite hydrogel on diabetic wound. The above experiments collectively demonstrate that our ADM-Fe3+@PA-Exos/GelMA hydrogel reliably overcomes the negative factors and accelerates diabetic wound healing, which provides a promising strategy to optimize ADM for diabetic wound treatment.