Fig. 5. Local treatment with hydrogels containing rifampin and a NLRP3 inflammasome inhibitor mitigates MRSA-induced inflammation.

(A) C57BL/6 mice were intra-articularly injected under the patella with DPBS (normal) and MRSA (4 × 10⁶ CFU). One day after infection, vancomycin (30 mg/kg) was administered for 3 days, after which a hydrogel (2%) containing OLT (200 μg per joint), rifampin (120 μg per joint), and OLT (200 μg per joint) + rifampin (120 μg per joint) (n = 3 to 10 per group) was injected intra-articularly under the patella. (B) Representative images of knee joints. (C) Blood was collected, and CBCs were measured. (D) The serum inflammatory profiles of septic joints were analyzed by PCA. The red box highlights factors that underwent significant change in the setting of infection. See fig. S9 for individual cytokines, chemokines, and other factors changes. (E) Synovial fluid cellularity was quantified, after which the presence of GFP-positive MRSA within the synovial cells was detected (scale bar, 100 μm). MRSA bioburden was quantified in CFU. (F) The synovial inflammatory profiles of septic joints were analyzed by PCA. The blue box highlights factors that underwent significant change in the setting of infection. See fig. S10 for individual cytokines, chemokines, and other factors changes. Error bars show means ± SD with individual data points. One- or two-way ANOVA with Tukey’s post hoc analysis was performed (*P < 0.05 or **P < 0.01). Photo credit: Photographer name: Hyuk-Kwon Kwon. Photographer institution: Yale University.