Abstract
Bacterial infection and its severe oxidative stress reaction will cause damage to skin cell mitochondria, resulting in long-lasting wound healing and great pain to patients. Thus, delayed wound healing in diabetic patients with Staphylococcus aureus infection is a principal challenge worldwide. Therefore, novel biomaterials with multifunction of bacterial membrane destruction and skin cell mitochondrial protection are urgently needed to be developed to address this challenge. In this work, novel gold cage (AuNCs) modified with epigallocatechin gallate (EGCG) were prepared to treat delayed diabetic wounds. The results showed that Au-EGCG had a high and stable photothermal conversion efficiency under near-infrared irradiation, and the scavenging rate of Au-EGCG for S. aureus could reach 95%. The production of large amounts of reactive oxygen species (ROS) leads to the disruption of bacterial membranes, inducing bacterial lysis and apoptosis. Meanwhile, Au-EGCG fused into hydrogel (Au-EGCG@H) promoted the migration and proliferation of human umbilical cord endothelial cells, reduced cellular mitochondrial damage and oxidative stress in the presence of infection, and significantly increased the basic fibroblast growth factor expression and vascular endothelial growth factor. In addition, animal studies showed that wound closure was 97.2% after 12 days of treatment, and the healing of chronic diabetic wounds was significantly accelerated. Au-EGCG nanoplatforms were successfully prepared to promote cell migration and angiogenesis in diabetic rats while removing S. aureus, reducing oxidative stress in cells, and restoring impaired mitochondrial function. Au-EGCG provides an effective, biocompatible, and multifunctional therapeutic strategy for chronic diabetic wounds.
Highlights
Long-lasting bacterial infection leads to severe oxidative stress and causes damage to skin cell mitochondria
The results showed that Au-epigallocatechin gallate (EGCG)@H possessed a high and stable photothermal conversion efficiency under near-infrared laser (NIR) irradiation, and the generation of a large amount of reactive oxygen species (ROS) led to the destruction of the bacterial membranes, thereby inducing bacterial lysis and apoptosis
It is worth mentioning that Au-EGCG@H significantly promoted wound healing in diabetic rats (Figure 6C)
Summary
Long-lasting bacterial infection leads to severe oxidative stress and causes damage to skin cell mitochondria. Diabetes can cause damage to the microvascular endothelium and result in tissue hypoxia and ischemia, delaying. The wound healing and leading to chronic non-healing (YoonYoona et al, 2016; Zhao et al, 2017; Vanaeia et al, 2021). For the treatment of bacterial infection, the main clinical choice is to use antibiotics, but the excessive use of antibiotics will inevitably lead to drug resistance. Because of the complex healing environment of diabetic skin wounds, it is very promising to develop a multifunctional nanoplatform that can effectively promote wound healing without causing drug resistance
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