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Intelligent microneedle patch with cobalt-iron Prussian blue nanozymes for accelerating diabetic wound healing via heme biosynthesis-driven immunomodulation
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DOI：10.1016/j.bioactmat.2026.04.005.png)
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Abstract
En 中文
A complex wound microenvironment with the presence of bacterial infection, overproduction of hydrogen peroxide (H2O2), chronic inflammation, poor vascularization and hypoxia wound result in delayed healing of diabetic wounds. In this study, a novel antibacterial microneedle patch integrating cobalt-iron Prussian blue (CFP) nanoenzymes loaded with prodrug 5-aminolevulinic acid (5-ALA) for intelligent, multi-stage therapeutic intervention on diabetic infected wound healing. Specifically, ALA@CFP demonstrated peroxidase (POD)-like activity to initiate the in situ production of hydroxyl radicals in response to elevated H2O2 in the wound, which proficiently induced bacterial ferroptosis and dismantled the bacterial biofilms, while the catalase (CAT)-like activity alleviated hypoxia wound conditions via decomposing H2O2 to produce oxygen. Simultaneously, Fe2+ released from ALA@CFP facilitated the transformation of 5-ALA to heme, significantly amplifying downstream heme oxygenase-1 (HO-1) activity and producing endogenous anti-inflammatory mediators, carbon monoxide and bilirubin. These molecules subsequently restructured the inflammatory wound microenvironment by instigating the polarization of macrophages from the M1-phenotype to the pro-repair M2-phenotype and upregulated the expression of anti-inflammatory factors, thereby fostering cell migration and angiogenesis. When embedded in a methacrylated gelatin/carboxymethyl chitosan hydrogel microneedle matrix, the system enables on-demand deep tissue delivery, achieving simultaneous antibacterial, anti-inflammatory, pro-angiogenic and regenerative effects in an infected diabetic mouse model. This study demonstrates a material-driven, metabolism-amplified strategy for intelligent wound repair, providing a promising platform for next-generation functional biomaterials.
Keywords:
Diabetic infected wound
Multifunctional microneedles
Enzyme-mimicking nanoparticles
Anti-inflammation
Bacterial ferroptosis
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