Biomaterial-based delivery of antimicrobial therapies for the treatment of bacterial infections.

The rise in antibiotic-resistant bacteria, including strains that are resistant to last-resort antibiotics, and the limited ability of antibiotics to eradicate biofilms, have necessitated the development of alternative antibacterial therapeutics. Antibacterial biomaterials, such as polycationic polymers, and biomaterial-assisted delivery of non-antibiotic therapeutics, such as bacteriophages, antimicrobial peptides and antimicrobial enzymes, have improved our ability to treat antibiotic-resistant and recurring infections. Biomaterials not only allow targeted delivery of multiple agents, but also sustained release at the infection site, thereby reducing potential systemic adverse effects. In this Review, we discuss biomaterial-based non-antibiotic antibacterial therapies for the treatment of community- and hospital-acquired infectious diseases, with a focus in in vivo results. We highlight the translational potential of different biomaterial-based strategies, and provide a perspective on the challenges associated with their clinical translation. Finally, we discuss the future scope of biomaterial-assisted antibacterial therapies. Web summary: The development of antibiotic tolerance and resistance has demanded the search for alternative antibacterial therapies. This Review discusses antibacterial biomaterials and biomaterial-assisted delivery of non-antibiotic therapeutics for the treatment of bacterial infectious diseases, with a focus on clinical translation.

Bacteriophage-Loaded Poly(lactic-co-glycolic acid) Microparticles Mitigate Staphylococcus aureus Infection and Cocultures of Staphylococcus aureus and Pseudomonas aeruginosa.

Lung infections caused by Gram-positive Staphylococcus aureus (S. aureus) and coinfections caused by S. aureus and Gram-negative Pseudomonas aeruginosa (P. aeruginosa) are challenging to treat, especially with the rise in the number of antibiotic-resistant strains of these pathogens. Bacteriophage (phage) are bacteria-specific viruses that can infect and lyse bacteria, providing a potentially effective therapy for bacterial infections. However, the development of bacteriophage therapy is impeded by limited suitable biomaterials that can facilitate effective delivery of phage to the lung. Here, the ability of porous microparticles engineered from poly(lactic-co-glycolic acid) (PLGA), a biodegradable polyester, to effectively deliver phage to the lung, is demonstrated. The phage-loaded microparticles (phage-MPs) display potent antimicrobial efficacy against various strains of S. aureus in vitro and in vivo, and arrest the growth of a clinical isolate of S. aureus in the presence of sputum supernatant obtained from cystic fibrosis patients. Moreover, phage-MPs efficiently mitigate in vitro cocultures of S. aureus and P. aeruginosa and display excellent cytocompatibility with human lung epithelial cells. Therefore, phage-MPs represents a promising therapy to treat bacterial lung infection.