Hybrid Probiotic Hydrogel With Curcumin-Loaded MnO2 Nanoparticles Enhances Diabetic Wound Healing Through Multimodal Microenvironmental Regulation AITranslate

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Skin wound injuries are often accompanied by bacterial infections and severe inflammation. Especially, M1-type macrophages at the wound site can trigger a cascade of inflammatory responses, mediating a vicious cycle of inflammation. Meanwhile, hypoxia further exacerbates vascular damage and constriction in the wound microenvironment, thereby impeding the healing process of infected wounds. To address this, we propose a “trinity” strategy integrating skin microbiota homeostasis regulation, immune microenvironment remodeling, and oxygen generation to promote blood flow for wound repair. A thermos-sensitive hydrogel was utilized to deliver nano-hybridized probiotics (LGG@NP-Gel). The hybrid probiotics were constructed by modifying Lactobacillus rhamnosus GG (LGG) with curcumin-loaded manganese dioxide. LGG exerts antibacterial effects through acid secretion and bioantagonism while promoting M2 macrophage polarization. The HMnO2 component releases curcumin, further enhancing M2 macrophage polarization. Additionally, HMnO2 scavenges reactive oxygen species (ROS) and generates oxygen, improving local oxygenation and blood supply to accelerate wound healing. In a murine wound model, LGG@NP-Gel significantly enhanced the healing efficacy.