Editors' ChoiceBIOMATERIALS

Bactericide hydrogel prevents orthopedic implant infections

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Science Translational Medicine  30 May 2018:
Vol. 10, Issue 443, eaau0463
DOI: 10.1126/scitranslmed.aau0463

Abstract

A hydrogel formulation adheres to exposed tissue and fracture surfaces to deliver antimicrobial enzymes for localized treatment and prevention of orthopedic implant infections.

Orthopedic implant infections are very difficult to treat because of the ability of the microbes to form small colony variants and biofilms. Staphylococci are dominant microorganisms at infection site, and current treatments include a combination of aggressive surgical debridement, implant removal, and long-term systemic antibiotic regimens with possible side effects. Johnson et al. engineered an injectable, bioadhesive hydrogel that sticks to implant site tissue and fracture surfaces. The hydrogel delivers an antimicrobial protein and prevents implant infection at femoral fractures.

Bacterial infection of orthopedic devices leads to the inability of fractures to heal, often leading to implant failure. The research team chose a protease-degradable hydrogel platform for in situ delivery of lysostaphin, an antimicrobial enzyme, which exhibits activity against antibiotic-resistant Staphylococcus aureus strains. The biomaterial is amenable to functionalization with bioadhesive peptides that support tissue integration. The hydrogel offers dual advantage: It releases lysostaphin in response to local cell-based enzymes and simultaneously biodegrades during tissue repair without the need for surgical retrieval. The team used multiple experimental approaches to establish the activity, stability, and release of hydrogel-encapsulated lysostaphin, shown to enhance antibiofilm activity. Specifically, an enzyme activity assay showed that the hydrogel maintains lysostaphin activity over two weeks. Injectable lysostaphin–delivering hydrogel outperformed prophylactic antibiotic treatment in clearing bacteria from infected fractures, facilitated fracture healing, and restored a sterile inflammatory environment in mouse models. The hydrogel was effective at reducing bacteria isolated from a pediatric case of osteomyelitis in vitro and antibiotic-resistant bacteria isolates in vivo. The authors speculate that localized delivery of antimicrobial components can prevent undesired immunological responses and changes to gut microbiome induced by systemic antibiotic treatments; however, this remains to be fully investigated. The results suggest that tissue adhesive hydrogels might be used in clinical setting for local delivery of antimicrobial agents. It also raises the interesting question of whether the hydrogel approach might help to solve the problem of recurrent infections in total joint arthroplasties and fracture fixation devices.

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