Anti-Infection and Immunoregulatory Multifunctional Hydrogel for Synergistic Treatment of Diabetic Wounds

Effective healing of diabetic wounds requires comprehensive management of bacterial infection, modulation of excessive inflammation, and promotion of cellular proliferation. Current clinical strategies include systemic blood glucose control combined with localized interventions such as debridement, antibiotic regimens, and advanced wound dressings. However, the efficacy of these strategies is often limited by challenges like antibiotic resistance. To overcome these challenges, we developed an anti-infection and immunoregulatory hydrogel loaded with two bioactive nanopreparations derived from Houttuynia cordata Thunb. (H. cordata). The one component, comprising carbon dots (CDs) synthesized via hydrothermal method using H. cordata and then modified with polyethylenimine (PEI) to form PEI-modified CDs (PCDs), demonstrates potent antibacterial activity. The other consists of plant-derived extracellular vesicles (EVs) that exhibit strong antioxidative and anti-inflammatory properties, effectively reducing reactive oxygen species levels, attenuating inflammatory responses, and promoting fibroblast proliferation and migration. These two components were co-incorporated into methylacrylated gelatin (GelMA) to form composite termed Gel@P&E. This system enables the sustained release of both PCDs and EVs, thereby coordinately regulating inflammation and facilitating tissue regeneration. In summary, this study successfully constructs multifunctional hydrogel platform that integrates anti-infective and immunoregulatory functions, presenting an alternative therapeutic strategy for diabetic wounds management.