Biologically Active Implants Prevent Mortality in a Mouse Sepsis Model.

Abstract

Implant-associated infections remain a significant complication in medicine. often leading to chronic infection, tissue damage, or implant failure. To address this, this work develops a modular, triple-action titanium implant that integrates bacterial repellency, bactericidal activity, and enhanced tissue integration. The implant comprises medical-grade titanium with a co-deposited layer of bacteriophages and collagen stably embedded within a repellent lubricant layer. The collagen layer promotes cell deposition and spreading in vitro. When tested against Pseudomonas aeruginosa, the coating reduces bacterial load by 3.2 logs on the surface and 1.9 logs in the medium, outperforming conventional liquid-infused surfaces. A modified version targeting Staphylococcus aureus achieves 4.1-log and 5.2-log reductions, respectively, after a 6-h incubation. When challenging the coating in a sepsis survival model of Pseudomonas aeruginosa infection, mice with the phage-activated implants exhibit a 100% survival rate and fully recover from the infection. In comparison, those with pathogen-repellent and untreated titanium implants show survival rates of only 30% and 10%, respectively. Furthermore, phage, but no bacteria, are detected in the bloodstream of mice implanted with phage-activated titanium, suggesting that locally implanted phage-biomaterials can distribute systemically to control blood infections. Therefore, the engineered phage-activated, triple-action biomaterials may prevent implant-associated infections locally and systemically.