Bacteriophage delivering hydrogels reduce biofilm formation in vitro and infection in vivo

Abstract

Implanted orthopedic devices become infected more frequently than any other implanted surgical device. These infections can be extremely costly and result in significant patient morbidity. Current treatment options typically involve the long term, systemic administration of a combination of antibiotics, often followed by implant removal. Here we engineered an injectable hydrogel capable of encapsulating Pseudomonas aeruginosa bacteriophage and delivering active phage to the site of bone infections. Bacteriophage retain their bacteriolytic activity after encapsulation and release from the hydrogel, and their rate of release from the hydrogel can be controlled by gel formulation. Bacteriophage-encapsulating hydrogels effectively kill their host bacteria in both planktonic and biofilm phenotypes in vitro without influencing the metabolic activity of human mesenchymal stromal cells. Bacteriophage-encapsulating hydrogels were used to treat murine radial segmental defects infected with P. aeruginosa. The hydrogels achieved a 4.7-fold reduction in live P. aeruginosa counts at the infection site compared to bacteriophage-free hydrogels at 7 days postimplantation. These results support the development of bacteriophage-delivering hydrogels to treat local bone infections.