AI-assisted phage formulation delivered via injectable hydrogels for localized control of implant-associated infections.

Abstract

Bacteriophages are emerging as highly effective antimicrobials for the treatment of persistent bacterial infections, offering precision-targeted action ideal for personalized medicine. Here, we present a scalable phage therapy platform specifically engineered for implant infections. Using an unsupervised machine learning-assisted clustering model, we selected phage combinations for enhanced antibacterial synergy that were delivered using a minimally invasive, shelf-stable composite hydrogel. The hydrogel was composed of laponite nanoclay and carboxymethyl cellulose, delivering a binary <i>Pseudomonas aeruginosa</i> phage cocktail. The phage cocktail-loaded composite nanoclay hydrogel achieved a 5-log bacterial reduction in a biofilm model, while <i>in vivo</i> studies in a murine implant infection model showed 100% survival of treated mice compared to 60% in controls. The composite phage-nanoclay hydrogel also demonstrated a 50% reduction in friction, maintained shelf-life of up to 18 months, and sustained phage release <i>in vivo</i>. Our results demonstrate the power of AI-assisted phage formulation paired with multifunctional biomaterials as a customizable and effective strategy for precision treatment of bacterial infections, advancing the clinical potential of phage therapy.