Infection-fighting Materials

Device-associated infections, such as catheter-associated bloodstream or urinary tract infections and surgical site infections, result in substantial morbidity and mortality and contribute significantly to the high cost of caring for patients. Current strategies with systemic antibiotics are generally ineffective in eradicating device-related infections due to the persistence of an infectious biofilm. Dr. García has engineered bacteriophage-delivering polymeric materials to reduce biomaterial-associated infections. Bacteriophages are viruses specific to bacteria causing lysis. The phage infection amplifies and propagates through the pathogen, but is self-limited in that it cannot infect eukaryotic cells, and is cleared when the host bacteria is eliminated. This provides on-demand response to pathogens, while reducing the development of antibiotic resistance. The García lab engineered phage-loaded polymeric microparticles that deposit throughout the lung via dry powder inhalation and deliver active phage. Phage-loaded microparticle effectively reduced bacterial infections and associated inflammation from healthy and cystic fibrosis mice and rescued mice from pneumonia-associated death. In a separate application, the García lab has engineered an injectable poly(ethylene glycol) hydrogel to deliver the bacteriolytic enzyme lysostaphin to treat bacterial infections in bone fractures. Lysostaphin-delivering hydrogels eradicated bacterial infection and out-performed prophylactic antibiotic and soluble lysostaphin therapy in a murine model of femur fracture. Importantly, infected fractures treated with lysostaphin-delivering hydrogels fully healed with equivalent bone formation and mechanical properties to uninfected fractures. Lysostaphin-delivering hydrogels eliminated antibiotic-resistant infections, supporting this therapy as an alternative to antibiotics.

  1. Dinjaski N, Suri S, Valle J, Lehman SM, Lasa I, Prieto MA, García AJ. Near-infrared fluorescence imaging as an alternative to bioluminescent bacteria to monitor biomaterial-associated infections. Acta Biomater 2014; 10:2935-44. PMC4041799.
  2. Johnson CT, Wroe JA, Agarwal R, Martin KE, Guldberg RE, Donlan RM, Westblade LF, García AJ. Hydrogel delivery of lysostaphin eliminates orthopedic implant infection by Staphylococcus aureus and supports fracture healing. Proc Natl Acad Sci USA 2018; 115:E4960-69. PMC5984524.
  3. Agarwal R, Johnson CT, Imhoff BR, Donlan RM, McCarty NM, García AJ. Inhaled bacteriophage-polymeric particles ameliorate acute lung infections. Nat Biomed Eng 2018; 2:841-49.
  4. Johnson CT, Sok MCP, Martin KE, Kalkar PP, Caplin JD, Botchwey EA, García AJ. Lysostaphin and BMP-2 co-delivery reduces S. aureus infection and regenerates critical-sized segmental bone defects. Sci Adv (in press).