A biomimetic core-shell nanofibrous dressing for temporally coordinated infection control and mitochondrial protection in diabetic wounds

Abstract

Chronic infected diabetic wounds are driven by a self-reinforcing pathological cycle of bacterial infection, oxidative stress, and immune dysregulation, wherein mitochondrial dysfunction contributes to impaired reparative macrophage polarization and angiogenesis. To address this, a skin-mimetic core-shell nanofibrous dressing (AT@PCS) was fabricated via coaxial electrospinning from a pullulan/quaternized chitosan (QCS) matrix, featuring a tannic acid (TA)-crosslinked shell for rapid barrier defense and an Astragalus polysaccharide (APS)-loaded core for sustained intracellular regulation. In vitro, the TA/QCS shell achieved >99.6% antibacterial efficiency against Escherichia coli and Staphylococcus aureus and rapidly scavenged extracellular reactive oxygen species (ROS). Subsequently, sustained APS release supported the activation of Nrf2-mediated antioxidant signaling, improved mitochondrial membrane potential, improved ATP production and mitochondrial respiratory function, and attenuated oxidative stress-induced glycolytic shift, thereby promoting M2 polarization and upregulating VEGF expression. These findings suggest that extracellular ROS scavenging alone is insufficient to fully reverse mitochondrial oxidative damage, underscoring the potential importance of intracellular redox regulation. In a diabetic rat full-thickness infected wound model, AT@PCS achieved 71.7 ± 4.4% wound closure by day 14, significantly superior to the 54.8 ± 3.4% closure rate of the control group, with markedly enhanced neovascularization and orderly collagen remodeling. This temporally coordinated biomimetic platform offers a strategy for coordinated regulation of redox balance, cellular metabolism, and immune microenvironment and provides a potential design strategy for diabetic wound repair.