Work

Intracellular bacteria-driven macrophage glycolysis in diabetic infected wounds: A hydrogel-based nanotherapy for targeting intracellular pathogens and modulating immune dysregulation

Year: 2025

Type: article

Abstract: Diabetic infected wounds (DIWs) are a significant clinical challenge, characterized by suboptimal treatment outcomes due to prolonged healing times, frequent recurrences, and high amputation rates. Recent studies have highlighted the role of intracellular bacteria, particularly Staphylococcus aureus , in driving macrophage dysfunction and sustaining chronic inflammation through glycolytic activation. To address this metabolic reprogramming, we utilized single-cell RNA sequencing to analyze the cellular composition of diabetic infected wounds and identified a distinct M1 macrophage subpopulation with upregulated glycolytic function. We developed a hydrogel formulation encapsulating cefalosporin-modified Atractylodes macrocephala extracellular vesicles to target intracellular pathogens and modulate macrophage polarization. The hydrogel demonstrated excellent biocompatibility, efficacy in eradicating intracellular bacteria, capacity to modulate macrophage polarization and metabolic reprogramming, and ability to promote angiogenesis and skin healing. In vitro and in vivo experiments confirmed its dual therapeutic effect of symptom relief and root cause resolution. This study provides insights into the crosstalk between intracellular bacteria and macrophages in DIWs and offers a promising therapeutic strategy for targeting intracellular pathogens and modulating immune dysregulation.

Source: Chemical Engineering Journal

DOI: 10.1016/j.cej.2025.171354