A Plaster-Like, Sequentially Triggered Bilayer Hydrogel Patch for Enhanced Diabetic Wound Management

Diabetic wounds, a common complication of diabetes, pose significant challenges in clinical management. Proactively targeting bacterial biofilms in chronic wounds can enhance anti-inflammatory efficacy, accelerate the transition from inflammation to tissue proliferation, and promote more efficient healing. In this study, a bilayer hydrogel patch (NIM@UP/CuS@BT gel) is developed for diabetic wound management. This innovative system comprises a glucose-responsive bottom layer containing copper sulfide (CuS) to deliver transient antibacterial and antibiofilm activity during the initial infection phase, and a stable upper layer incorporating nimesulide (NIM) to provide sustained anti-inflammatory effects throughout the subsequent healing phase. This results demonstrate that the upper layer of the hydrogel patch exhibits enhanced mechanical strength of 146.3 ± 18.9 kPa, offering robust physical protection similar to a plaster. Additionally, the patch exhibits satisfied antibacterial performance, achieving over 95% bactericidal efficacy against both Escherichia coli ( E. coli ) and Staphylococcus aureus ( S. aureus ), with an in vivo bactericidal rate of 78.7%. Furthermore, the downregulation of pro-inflammatory cytokines tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) and the upregulation of the anti-inflammatory cytokine interleukin-10 (IL-10) confirms its potent anti-inflammatory properties. In summary, the bilayer hydrogel system exhibits high biocompatibility, antibacterial and anti-inflammatory capabilities, addressing the distinct needs of different stages in the wound healing process.