Formulation and evaluation of hydrogel based on Brazilian propolis ethanol extract for promoting diabetic wound healing

Diabetes wounds represent a significant clinical challenge, primarily attributed to their complex microenvironment characterized by persistent inflammation, heightened infection susceptibility, and impaired angiogenesis. To address these interconnected challenges, a multifunctional hydrogel dressing (designated EEP/PS) was constructed using pullulan, Brazilian propolis ethanolic extract, and polyvinyl alcohol. This biomaterial exhibits an interconnected porous structure, suitable mechanical properties, tissue adhesion, remarkable thermal stability, excellent sustained-release and swelling capacity. Notably, EEP/PS shows potent antioxidant capability and significantly enhances cell migration in hydrogen peroxide-induced oxidative injury models. Furthermore, the hydrogel downregulates the expression and secretion of key pro-inflammatory cytokines in LPS-stimulated macrophages, including tumor necrosis factor-α, interleukin-6, and interleu-kin-1β. The hydrogel also exhibits broad-spectrum antibacterial efficacy against common wound pathogens Escherichia coli and Staphylococcus aureus. In a diabetic rat model, EEP/PS accelerated wound closure by synergistically promoting reepithelialization, collagen deposition, angiogenesis while mitigating local inflammation. Additionally, EEP/PS exhibits an excellent hemostasis capacity and bio-compatibility, critical for clinical translation. Collectively, these findings highlight the translational potential of EEP/PS as a multifunctional biomaterial for diabetic wound care.