Injectable Electrospun Hydrogel with Antimicrobial, pH Sensing Nanoparticles for Local Infection Control and Monitoring

Abstract

Most antimicrobial drug candidates currently in development are derivatives of established antibiotic classes. In contrast, antimicrobial heteroatom-doped carbon quantum dot (COD) nanoparticles vastly differ from their chemical antibiotic counterparts and exhibit potent antibacterial activity and favourable biocompatibility, representing a promising alternative strategy, particularly for topical applications. Here, we report the incorporation of cobalt-doped carbon quantum dots (Co-CODs) into injectable, biocompatible hydrogels capable of both sensing pH and eliminating bacteria. Ultrasmall Co-CODs demonstrated broad-spectrum activity against gram-positive Methicillin-resistant Staphylococcus aureus (MRSA) and Gram-negative Pseudomonas aeruginosa (PAO1), mediated by membrane hyperpolarisation and reactive oxygen species (ROS) induced membrane damage. The particles showed negligible effect on primary fibroblast and endothelial cell viability at concentrations that were bactericidal to MRSA. Polymeric hydrogels were fabricated via electrospinning of chitosan, polyvinylpyrrolidone (PVP), and polyvinyl alcohol (PVA) polymer blends incorporating Co-COD and pH-responsive HPTS particles. This approach provided accurate measurement of environmental pH within the physiological range observed across healthy and chronic wounds. In vivo, the injectable hydrogels exhibited robust antimicrobial efficacy against MRSA without impairing wound closure relative to untreated controls, while also reducing inflammatory immune responses in infected tissues. Collectively, these findings demonstrate the potential of ultrasmall metal-doped CODs for infection control and their integration into 3D matrices as multifunctional theragnostic platforms. ToC (<60 words describe the main results)Ultrasmall antimicrobial carbon nanoparticles were incorporated into polymeric hydrogels containing a pH-responsive probe. This platform enabled detection across a physiologically relevant pH range of 5.0-6.5, spanning conditions associated with both healthy healing and chronically infected wounds. The hydrogel demonstrated strong antibacterial activity by generating damaging reactive oxygen species, and, in mice, effectively controlled infection while reducing pro-inflammatory immune responses. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=171 SRC="FIGDIR/small/736887v1_ufig1.gif" ALT="Figure 1"> View larger version (41K): org.highwire.dtl.DTLVardef@1a52b32org.highwire.dtl.DTLVardef@b6eed2org.highwire.dtl.DTLVardef@1f94143org.highwire.dtl.DTLVardef@12b9ff3_HPS_FORMAT_FIGEXP M_FIG O_FLOATNOScheme 1:C_FLOATNO Antimicrobial nanoparticle-doped hydrogel glows in alkaline wound conditions which are representative of chronic infections. Once in the wound bed, the hydrogel removes all MRSA infection, reducing inflammatory macrophage (iNOS) and neutrophil (MPO) populations, and restores healthy wound collagen deposition. C_FIG