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.