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Metal Ion-Releasing Glass Particles to Enhance Antibiotic Efficacy Against Cystic Fibrosis Infection

Wolverton, M.; Cheng, Z.; Boyd, D.; Leung, B. M.

2025-10-31 bioengineering
10.1101/2025.10.30.685604 bioRxiv
Show abstract

Cystic fibrosis is characterized by thickened airway mucus that impairs mucociliary clearance and promotes persistent bacterial infections. These chronic infections, primarily caused by Pseudomonas aeruginosa and Staphylococcus aureus, lead to progressive lung damage and respiratory failure, which are the leading causes of mortality in cystic fibrosis patients. Although antibiotics remain the cornerstone of treatment for such airway infections, incomplete bacterial eradication often contributes to the emergence of antibiotic resistance. This study explores whether the efficacy of conventional antibiotics can be enhanced through co-delivery with antibacterial metal ions released from borate-based bioactive glasses. To evaluate this combination therapy, we developed an in vitro airway infection model that replicates key features of the cystic fibrosis airway environment. The model incorporates a layer of bronchial epithelial cells, a mucus-like hydrogel, and bacteria deposited using an aqueous two-phase system. Multiple bioactive glass formulations were evaluated for their ability to augment antibiotic activity and enhance bacterial eradication. The results demonstrated additive or synergistic antibacterial effects against P. aeruginosa and S. aureus, while maintaining mammalian cell viability. These findings suggest that metal ion-antibiotic combination therapies delivered via bioactive glasses may improve treatment outcomes for cystic fibrosis-related infections and reduce reliance on high-dose or prolonged antibiotic regimens. Such approaches hold promise not only for cystic fibrosis patients but also for broader clinical applications where antibiotic resistance is a growing concern.

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