Development and characterization of metformin hydrochloride hydrogels as potential wound dressings for diabetic foot...

Diabetic foot ulcers are a severe complication of diabetes mellitus, characterized by chronicity and high risk of infection. Their effective management requires wound-specific dressings, as no universal system adequately addresses the full spectrum of wounds. Hydrogel dressings offer promising local therapeutic strategies; however, materials combining mechanical robustness, prolonged drug release, and microenvironment modulation remain limited. Herein, we present a rational design strategy for a physically crosslinked, multi-component PVA-based hydrogel membrane incorporating metformin hydrochloride (MET) as the active pharmaceutical ingredient. Although conventionally administered orally, MET has been increasingly recognized for its anti-inflammatory and pro-regenerative properties, supporting its repurposing for localized wound applications. The developed dressings were comprehensively characterized in terms of rheology, pH modulation, morphology (optical microscopy, SEM), mechanical performance, liquid uptake, MET release, cytocompatibility, and in vitro antibacterial and anti-inflammatory activity. An optimized hydrogel formulation based on PVA (Mw ∼ 195,000 Da) and six freeze-thaw cycles (-80 °C/∼22 °C) exhibited high elasticity (ε > 380%), tensile strength (σ ∼ 0.23 MPa), and minimal permanent deformation (ε ≤ 3%). It enabled prolonged MET release over 72 h while maintaining a mildly acidic environment (pH ∼ 5.5-6.3) favorable for wound healing. Compared with commercial drug-free hydrogel dressings, the optimized formulation showed superior mechanical strength, pH-modulating capacity, antibacterial activity against Escherichia coli and Pseudomonas aeruginosa, as well as attenuation of IL-6 expression in LPS-stimulated keratinocytes, indicating anti-inflammatory activity. Collectively, these findings highlight the early-stage potential of MET-loaded solid-sheet hydrogels as multifunctional dressings for chronic, low-exudate diabetic foot ulcers.