Fig. 6. Local treatment with hydrogels containing rifampin and a NLRP3 inflammasome inhibitor prevents the development of MRSA-induced septic arthritis.

C57BL/6 mice were intra-articularly injected under the patella with DPBS (normal) and MRSA (4 × 10⁶ CFU). After a day, vancomycin (30 mg/kg) was administered for 3 days, after which a hydrogel (2%) containing OLT (200 μg per joint), rifampin (RI; 120 μg per joint), and OLT (200 μg per joint) + rifampin (120 μg per joint) (n = 4 to 10 per group) was injected intra-articularly under the patella. (A) Representative 3D images of the knee and involucrum along the axial plane (AX) and 2D images in the coronal (COR), sagittal (SAG), and axial planes were reconstructed by micro-CT. BV/TV and TMD of cortical and cancellous bone in the tibia were quantified by micro-CT; BV/TV and TMD of cortical and cancellous bone in the femur (fig. S6C). BV/TV and Conn-Dens. of the tibial involucrum were quantified by micro-CT; BV/TV and conn-dens. of involucrum in the femur (fig. S6, A and B). (B) Paraffin-embedded tissue sections were stained with H&E and SAF O, from which inflammation score, synovial hyperplasia, OARSI score, osteophyte size, cartilage degradation, bone erosion, and bone formation were calculated and scored (scale bar, 1000 μm). Error bars show means ± SD with individual data points. (C) Illustrated summary of the various symptoms of MRSA-induced septic arthritis and the effects of local rifampin and NLRP3 inflammasome inhibitor hydrogel treatment. Error bars show means ± SD with individual data points. One- or two-way ANOVA with Tukey’s post hoc analysis was used (*P < 0.05 or **P < 0.01).