Prosthetic joint infection (PJI) is a devastating complication of joint arthroplasty, with an incidence rate of 0.25–2.0% for primary total hip and knee replacements. The infection incidence rate increase to 3.2–5.6% in revision surgery. These infections tend to be chronic as they resist innate and adaptive immune defense mechanisms as well as antibiotics, and the treatment of biofilm infections presents a considerable unmet clinical need. There is evidence that over 50% of bacteria reside in biofilms, with staphylococci (specifically Staphylococcus aureus and Staphylococcus epidermis) being the most common biofilm-forming bacteria of bone allografts. To overcome infection-related problems linked to the use of bone allografts, we proposed a novel magnetic hyperthermia therapetic method to eradicate biofilm form prosthetic joint infection.
The fabricated magnetic nanoparticles was core-shell compositions with Fe3O4 inside and 250 ~300 nm in diameter by dynamic light scattering (DLS). The thermal effect of nanoparticles was demonstrated in AC magnetic field >0.01 T, frequency >100 KHz with controllable magnetic hyperthermia effect. Also, the hemolytic properties of nanoparticles were assessed according to ASTM756-08 method to prove the biocompatibility. In vitro efficacy of magnetic hyperthermia to S. aureus or methicillin-resistant S. aureus (MRSA) biofilm was evaluated by bacterial counting method. In vivo efficacy was evaluated on S. aureus infected SD rat PJI model by intra-operative intra-articular method. In the PJI model, the SD rats were treated with combine heat-stable vancomycin and iron oxide nanoparticles with magnetic hyperthermia, showed significant effect than S. aureus infected group (n=7–9) (P value <0.005).
In this study, the magnetic nanoparticles behave as magnetic guided thermal agent, stable chemical-physical property for 3 months, can be localized intra articular and magnetic drive to destroy the biofilm in the artificial joint surface. The controllable hyperthermia method is suitable heat stable antibiotics application. Optimization the application dosage or frequency of iron oxide nanoparticles and parameter of hyperthermia can potentially cure the PJI disease. Magnetic hyperthermia method can potentially prevent serious infection on post-surgery maintenance of knee replacements application.
References:
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