Bimetallic Nanozymes/Polypyrrole/Methylene Blue Platform for Photothermal and Catalytic Biofilm Disruption and Angiogenesis Enhancement in Diabetic Wound Healing

Diabetic wounds pose a significant challenge due to impaired tissue regeneration, prolonged inflammation, poor oxygen supply, and microbial infections. Methicillin-resistant <i>Staphylococcus aureus</i> (MRSA) infections delay healing by prolonging inflammation and increasing antimicrobial resistance. To develop an effective antibiotic alternative, multifunctional nanocomposites, ceria-zinc nanoflowers (CeZn@PPY@MB NFs) bearing a polypyrrole (PPY) coating loaded with methylene blue (MB) are developed, to address the multifaceted requirements for healing diabetic wounds. Due to the synergistic effects of photothermal, catalysis, and reactive oxygen species (ROS) generation,CeZn@PPY@MB NFs exhibit robust antibacterial activity with high collagen deposition and angiogenesis. The nanoflowers, with a high surface area of water lily-like morphology, are confirmed through scanning electron microscopy, energy-dispersive X-ray analysis, X-ray photoelectron spectroscopy, and X-ray diffraction analysis. PPY/MB-mediated synergistic photothermal effect, ROS generation, and catalytic activities lead to robust MRSA killing and biofilm disruption. Nanoflowers demonstrate rapid wound healing due to reduced inflammation, tissue regeneration, and angiogenesis in the diabetes-induced wound model by modulating tumor necrosis factor-α, CD-44, Ki-67, collagen deposition, ROS, interleukin-1β (IL-1β), IL-8, and IL-6 expression. Therefore, the developed multifunctional hybrid-metallic nanoflowers provide an advanced nanotherapeutic platform to eradicate MRSA effectively, offering a promising alternative to antibiotic therapy for managing resistant bacteria-infected diabetic foot ulcers.