Freeze-Killed M2 Macrophage-Encapsulated MXene Nanocomposites for Multifunctional Photothermal Therapy in Diabetic...

Diabetic wound healing remains a significant clinical challenge because of persistent inflammation, excessive oxidative stress, and bacterial infection. This study aimed to develop a biomimetic nanocomposite with multifunctional properties of antioxidation, antibacterial activity, anti-inflammation, and pro-angiogenesis for photothermal synergistic repair of diabetic wounds.

Freeze-killed M2 macrophages were used to encapsulate MXene nanoparticles to prepare a biomimetic composite material (abbreviated as MM). Its structural characteristics, protein retention, and photothermal performance were characterized and analyzed. The anti-inflammatory, antioxidant, antibacterial, and pro-angiogenic abilities of the material were evaluated in vitro. A streptozotocin (STZ)-induced diabetic mouse wound model was established to systematically assess the effects of MM combined with near-infrared light (NIR) on wound healing, collagen deposition, and in vivo inflammation regulation.

MM successfully preserved the cellular structure and functional proteins of M2 macrophages and exhibited excellent photothermal conversion performance. In vitro, it significantly inhibited pro-inflammatory cytokine secretion, scavenged reactive oxygen species, efficiently eliminated Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus), and effectively promoted angiogenesis. In vivo experiments demonstrated that MM combined with NIR irradiation accelerated diabetic wound closure, enhanced collagen deposition, and induced macrophage polarization toward the anti-inflammatory M2 phenotype, with favorable biocompatibility and no obvious toxicity at the experimental dose.

Freeze-killed M2 macrophage-encapsulated MXene nanocomposites can synergistically modulate the three key pathological hallmarks of diabetic wounds: persistent inflammation, oxidative stress, and bacterial infection. Triggered by NIR, they exert potent reparative effects, offering a safe, multifunctional, and translationally promising therapeutic strategy for chronic diabetic wounds.