A Bilayer Theranostic Hydrogel Integrating Visual pH Monitoring with Synergistic Diabetic Wound Healing Treatment

Abstract

Diabetes-related chronic wounds are difficult to heal due to persistent bacterial infection, disrupted pH homeostasis, and prolonged excessive inflammation. Consequently, effective wound monitoring and treatment integrated platforms are an urgent unmet demand to enable real-time assessment of wound progression and healing status. Herein, a bilayer theranostic hydrogel was developed as a wound dressing to achieve simultaneous infection monitoring and pathological micro-niche regulation. The therapeutic lower layer employed gelatin methacryloyl (GelMA), which incorporated quercetin-loaded liposomes (QLs) to sustain suppression of inflammatory stress and improvement of glycemic regulation. The coordination interactions between copper ions and sodium alginate (SA) constituted a secondary network within the hydrogel, enhancing its antibacterial potential and mecha-nical strength. Monitoring pH alterations in wound niches can predict early infection and inflammation risk, thereby facilitating the optimization of wound management. Hence, the monitoring layer integrated bromothymol blue (BTB) as a pH indicator, enabling visual detection of pH variations and providing real-time feedback during healing. In a diabetic rat full-thickness wound model, the bilayer hydrogel significantly accelerated chronic wound closure. Through integrating wound monitoring with antibacterial and anti-inflammatory dual functions, this multifunctional dressing provides insights for efficient healing and comprehensive assessment of diabetes-related chronic wounds.