Hydrogel delivery of lysostaphin eliminates orthopedic implant infection by Staphylococcus aureus and supports fracture healing

Abstract

SignificanceOrthopedic implant infections require long-term antibiotic therapy and surgical debridement to successfully retain the implant; however, therapeutic failure can lead to implant removal. Here an injectable PEG-based hydrogel that adheres to exposed tissue and fracture surfaces is engineered to deliver the antimicrobial enzyme lysostaphin to infected, implant-fixed, mouse femoral fractures. Lysostaphin encapsulation within the hydrogel enhances enzyme stability while providing enhanced antibiofilm activity and serving as a controlled delivery platform. In a preclinical animal model of orthopedic-implant infection, we show that lysostaphin-delivering hydrogels outperform prophylactic antibiotic therapy and soluble lysostaphin, by eradicating infection while promoting bone repair. Importantly, lysostaphin-delivering hydrogels are effective against antibiotic-resistant infections. This lysostaphin delivery platform could be highly effective at treating and preventing implant infections.

Impact of Bacterial Infections on Osteogenesis: Evidence From In Vivo Studies

“…In comparison to systemic treatment, the coating of osteosynthesis plates with antibacterial agents has resulted in more successful bacterial killing and prevention of implant infections. In these specific models, similar healing can be seen as in non‐infected controls …”

“…The radiographic or micro‐CT outcomes of the studies show that the defects generally bridge uneventfully under aseptic conditions. Strikingly, in spite of the relatively small defects that are often created, many studies report non‐union at follow‐up once a chronic infection is established . This negative influence of bacterial infection on healing depends on the severity of infection, and correlates with the initial bacterial inoculation dose .…”

“…This negative influence of bacterial infection on healing depends on the severity of infection, and correlates with the initial bacterial inoculation dose . In comparison, normal defect healing is often reported in cases where antibacterial treatment successfully eliminated all bacteria from the defect site …”

“…Strikingly, in spite of the relatively small defects that are often created, many studies report non-union at follow-up once a chronic infection is established. 25,34,43,44,64,68,[74][75][76] This negative influence of bacterial infection on healing depends on the severity of infection, 23,43,44,66,77,78 and correlates with the initial bacterial inoculation dose. 43 In comparison, normal defect healing is often reported in cases where antibacterial treatment successfully eliminated all bacteria from the defect site.…”

“…43 In comparison, normal defect healing is often reported in cases where antibacterial treatment successfully eliminated all bacteria from the defect site. 65,76,77…”