A diabetic microenvironment targeted nano-hydrogel loaded with quercetin and EGF for integrated synergistic bacteriostasis and proliferation-promoting diabetic infected wound repair.
Abstract
The diabetic wound microenvironment is characterized by high levels of reactive oxygen species (ROS), persistent inflammation, and high susceptibility to infection, greatly hindering the therapeutic efficacy of traditional treatments. In this study, a multifunctional hydrogel (PPS/QR-EGF-Gel) incorporating ROS-responsive quercetin nanoparticles (PPS/QR) and epidermal growth factor (EGF) was developed to accelerate the repair of diabetic infected wounds. The synthesized hydrogel was designed with a dual-action mechanism: in response to the high-ROS environment, the PPS nanoparticles undergo cleavage, which not only releases quercetin (QR) to exert its broad-spectrum antibacterial, antioxidant, and anti-inflammatory effects, but also generates nanoparticle fragments that help maintain the bioactivity of the co-delivered EGF. This preservation of EGF's activity significantly enhances its synergistic action with QR, robustly promoting cell proliferation, migration, and angiogenesis. As verified by in vitro experiments, the PPS/QR-EGF-Gel significantly inhibited pathogens including methicillin-resistant Staphylococcus aureus (MRSA, with a bactericidal rate of 81.3-85.4%), decreased ROS levels, and accelerated the proliferation and migration of HaCaT cells and human umbilical vein endothelial cells (HUVECs). In a diabetic rat model, the hydrogel apparently improved the wound closure rate, reduced the levels of inflammatory factors, and enhanced collagen deposition and angiogenesis. Moreover, proteomics analysis revealed that its superior combined therapeutic effects were achieved by suppressing the NF-κB inflammatory pathway and activating the EGFR/PI3K/AKT/VEGF pathway. This study provides a purification-repair integrated intelligent treatment strategy for diabetic infected wounds, demonstrating both clinical translation potential and broad applicability.
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