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 Pseudomonas aeruginosa phage cocktail. The phage cocktail-loaded composite nanoclay hydrogel achieved a 5-log bacterial reduction in a biofilm model, while in vivo 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 in vivo . 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. • AI-assisted genomic clustering model designed optimized phage cocktails. • Composite shear-thinning hydrogel enabled localized, injectable delivery. • Sustained phage release ensured prolonged antibacterial activity in vitro and in vivo . • Phage-hydrogel treatment achieved 100% survival of treated mice in an infected subcutaneous implant model.
Bayat et al. (Tue,) studied this question.