Nanozyme-Engineered Probiotic Microneedle Patch for Chronic Diabetic Wound Therapy

Chronic diabetic wounds are notoriously difficult to heal due to persistent bacterial infection, oxidative stress, and tissue hypoxia. Here, a multifunctional probiotic microneedle (MN) patch embedding platinum nanozyme-engineered Bacillus subtilis (Pt-M@B. sub) within a dissolvable, biocompatible polymer matrix is presented for synergistic diabetic wound therapy. This biohybrid system alleviates reactive oxygen species (ROS), combats bacterial infection, relieves hypoxia, and exerts anti-inflammatory effects. The platinum nanozyme modification protects the probiotics of B. subtilis by scavenging ROS and generating oxygen in situ, thereby enhancing probiotic survival and function under harsh wound conditions. Upon transdermal application, the MN patch (termed Pt-M@B. sub MN patch) enables efficient, minimally invasive delivery of the therapeutic nanozyme-modified probiotics directly into the wound bed, where the functionalized living material significantly suppressed Staphylococcus aureus infection, reduced inflammation, promoted collagen deposition and angiogenesis, and accelerated wound closure. Biosafety assessments confirmed excellent biocompatibility and systemic safety of the probiotic MN patch. Moreover, the patch exhibited efficient skin penetration and drug delivery in human cadaver skin, indicating strong clinical translation potential. Overall, this work introduces a robust living-materials-based strategy that integrates microbial therapy with catalytic nanotechnology for effective management of chronic infected wounds.