Dual chitosan hydrogel and polylactic acid microparticle delivery system reduces Staphylococcal osteomyelitis and soft tissue infection

Osteomyelitis, an infection of bone, is traditionally treated with long-term, systemic, high-dose antibiotics, which can lead to kidney and liver damage and accelerate the development of antibiotic resistance. Localized delivery may mitigate these risks by delivering antimicrobial(s) directly to the site of infection. Herein, innately antimicrobial chitosan hydrogel (CH) containing polylactic acid (PLA) microparticles, each loaded with fosfomycin antibiotic, was used to combat a biofilm-forming strain of Staphylococcus aureus. This dual CH + PLA biomaterial treatment mitigated S. aureus in planktonic and biofilm form in vitro, and in a clinically relevant, implant-associated rat model of chronic osteomyelitis. Notably, only the CH + PLA biomaterial treatment led to a reduction in bone defect area, plasma haptoglobin level, and bacterial burden in bone and soft tissue, compared to hydrogel only. Local treatment of osteomyelitis with the chitosan+microparticle vehicle loaded with fosfomycin mitigated S. aureus pathogenesis and may serve as an effective alternative to systemic antibiotics.