Functionalized carbon nanotube microphere-pullulan polysaccharide hydrogel for electric-photothermal immunomodulation and sequential repair of diabetic infected wounds

Chronic diabetic wounds display complex pathologies involving bacterial invasion, oxidative stress dysregulation, persistent inflammation, and impaired endogenous bioelectricity, which collectively amplify inflammatory cascades, suppress angiogenesis, and induce aberrant fibrosis. These events hinder tissue regeneration and trigger pathological scarring, which poses a critical clinical challenge. Conventional dressings with limited functionality and microenvironment adaptability cannot achieve synergistic interventions against multiple wound pathologies. Herein, we develop a multifunctional PI-CM@AP hydrogel with photothermal-triggered drug delivery and biomimetic conductivity. The hydrogel matrix was formed via aldehyde-hydroxyl acetal cross-linking of sodium periodate-oxidized pullulan, as spectroscopically verified, with uniformly incorporated astragalus polysaccharide-loaded carbon nanotube microspheres (CM@AP). The optimized hydrogel exhibited favorable injectability, self-healing capacity, and tissue adhesion. Pullulan enables conformal coverage of irregular wounds, while dispersed CM@AP imparts biomimetic conductivity. The engineered conductive microenvironment is hypothesized to couple with endogenous bioelectric signals, potentially facilitating directional cell migration and skin regeneration. Combining NIR photothermal sterilization, Zn 2+ antibacterial activity, and pH-responsive astragalus polysaccharide release, PI-CM@AP establishes a synergistic “photothermal-ion-drug” system to eliminate pathogens and mitigate infection-driven inflammatory deterioration. In vitro, the hydrogel scavenged excess ROS, which is associated with inhibited NF-κB inflammation and modulated Nrf2/HO-1 axis activity, thereby promoting M1-to-M2 macrophage polarization and remodeling an anti-inflammatory, antioxidative microenvironment. Its treatment is correlated with altered HIF-1α/VEGF signaling, which may facilitate endothelial migration and vascular reconstruction, whereas conductivity-associated regulatory mechanisms remain unvalidated. Rat diabetic infected wound models validated the favorable biosafety of PI-CM@AP. The hydrogel inhibits NF-κB cascades and TGF-β-induced Smad2/3 phosphorylation, alleviating pathological fibrosis and achieving high-quality scar-attenuated wound regeneration. Collectively, the integration of photothermal immunomodulation and biomimetic conductivity enables the hydrogel to mediate multi-target sequential repair of chronic diabetic wounds. This study offers a promising strategy for designing advanced wound-healing dressings. Schematic diagram demonstrating the therapeutic mechanism of CM@AP biomaterial against infected diabetic wounds. Constructed from zinc nitrate, AP and pullulan dialdehyde, the CM@AP system under near-infrared light can synergize with the endogenous electric field at the wound site. This integrated system achieves broad-spectrum antibacterial effect, orchestrates immunomodulation to drive M2 macrophage polarization, facilitates angiogenesis, and suppresses excessive scar formation, thereby comprehensively promoting the repair of refractory infected diabetic wounds.