Isoliquiritigenin micellar microneedle for pH monitoring and diabetic wound healing

Chronic inflammation, oxidative stress, and insufficient angiogenesis hinder wound healing in patients with diabetes, necessitating long-term management strategies. In this study, we developed pH-responsive hydrogel microneedles (LSI-GCA) based on <i>Lycium barbarum</i> polysaccharide stearate micelles that could achieve real-time pH monitoring and intelligent drug release for effective wound management. LSI-GCA was prepared through hydrophobic modification and isoliquiritigenin (ISO) loading, followed by its combination with a chitosan/anthocyanin backing layer. LSI-GCA exhibited excellent biocompatibility and antibacterial and antioxidant properties by activating the NRF2 pathway and inhibiting pro-inflammatory factors. Animal experiments confirmed that LSI-GCA significantly accelerated wound healing in a diabetic model and promoted angiogenesis, collagen deposition, and M2 macrophage polarization. Genomic and network pharmacological analyses revealed a multi-target synergistic mechanism involving the modulation of EGFR/VEGF signaling to promote proliferation, inhibition of inflammatory pathway (NF-κB), and repair of DNA damage through upregulation of BRCA1/2. This study provides an integrated "monitoring-treatment" strategy for diabetic wounds, offering great potential for clinical transformation and personalized treatment.