Co-delivery of therapeutic bacteriophages and aztreonam via core-shell electrospun fibers for synergistic action against Pseudomonas aeruginosa infections.

The global rise of antimicrobial resistance poses a persistent challenge in chronic wound care, where limited perfusion and biofilm-embedded bacterial communities severely restrict the efficacy of conventional antibiotics. Despite renewed interest and promising approaches, bacteriophage-based therapy remains constrained by intrinsic phage susceptibility to complex wound environments and the emergence of phage resistance. While synergistic pairings of phages and antibiotics offer a compelling strategy to counteract these limitations, the lack of systems capable of protecting and delivering respective pairs continues to impair clinical translation. To address these challenges, we developed an electrospun nanofiber-based co-delivery platform that spatially separates the lytic bacteriophage JG004 and the β-lactam antibiotic aztreonam within a protective core-shell matrix. The nanofibers exhibit high mechanical robustness, maintain phage viability for at least 28 days, and enable rapid release of both antimicrobials, while reducing exposure to environmental and oxidative stresses. In vitro assays revealed pronounced phage-antibiotic synergy, achieving up to 99% bacterial reduction of Pseudomonas aeruginosa, outperforming the corresponding monotherapies in treatment of both planktonic and biofilm-associated bacteria. Additionally, the modular architecture of our delivery system enables flexible integration of alternative phage-antibiotic pairings, enabling rapid adaptation to patient-specific pathogens and resistance profiles. By combining sustained antimicrobial performance with a clinically adaptable delivery system, this nanofiber platform offers a promising route towards personalized infection management and supports the clinical integration of phage-based strategies into modern wound care.