Longitudinal Model of Periprosthetic Joint Infection in the Rat

Abstract

The majority of periprosthetic joint infections occur shortly after primary joint replacement (<3 months) and require the removal of all implant components for the treatment period (~4 months). A clinically relevant animal model of periprosthetic infection should, therefore, establish an infection with implant components in place. Here, we describe a joint replacement model in the rat with ultrahigh molecular weight polyethylene (UHMWPE) and titanium components inoculated at the time of surgery by methicillin-sensitive Staphylococcus aureus (S. aureus), which is one of the main causative microorganisms of periprosthetic joint infections. We monitored the animals for 4 weeks by measuring gait, weight-bearing symmetry, von Frey testing, and micro-CT as our primary endpoint analyses. We also assessed the infection ex vivo using colony counts on the implant surfaces and histology of the surrounding tissues. The results confirmed the presence of a local infection for 4 weeks with osteolysis, loosening of the implants, and clinical infection indicators such as redness, swelling, and increased temperature. The utility of specific gait analysis parameters, especially temporal symmetry, hindlimb duty factor imbalance, and phase dispersion was identified in this model for assessing the longitudinal progression of the infection, and these metrics correlated with weight-bearing asymmetry. We propose to use this model to study the efficacy of using different local delivery regimens of antimicrobials on addressing periprosthetic joint infections. Statement of clinical significance: We have established a preclinical joint surgery model, in which postoperative recovery can be monitored over a multi-week course by assessing gait, weight-bearing, and allodynia. This model can be used to study the efficacy of different combinations of implant materials and medication regimens.

Targeting cancer stem cells by disulfiram and copper sensitizes radioresistant chondrosarcoma to radiation

“…Radiographs of tibia tumors were obtained by a Faxitron Portable X-Ray cabinet (Hewlett Packard, McMinnville, OR, USA), with imaging film (Portal Pack PPL-2, Merry X-Ray Corporation, San Diego, CA). The output voltage was 90 kVp and the exposure time was 7s [ 26 ]. Once the tumor became palpable, tumor sizes were measured by digital calipers and calculated by tumor volume = ½ × length × width 2 .…”

Review of immunological plasma markers for longitudinal analysis of inflammation and infection in rat models

“…Red arrows indicate the presence of septic loosening, and arrowheads indicate peri‐implant radiolucency. Adapted from Fan et al 51 [Color figure can be viewed at wileyonlinelibrary.com]…”

Tissue‐level cytokines in a rodent model of chronic implant‐associated infection

“…This dose was chosen based on previous models to create a chronic localized infection but to avoid systemic sepsis. 36 Additionally, a previous study found that inflammation due to surgery can persist until the 21-day time point, so this time point was chosen for tissue collection to optimize the measurement of infection-specific inflammatory cytokine responses. 36 Body temperature was monitored throughout the 21-day time period for the presence of fever to ensure no systemic sepsis occurred.…”

“…36 Additionally, a previous study found that inflammation due to surgery can persist until the 21-day time point, so this time point was chosen for tissue collection to optimize the measurement of infection-specific inflammatory cytokine responses. 36 Body temperature was monitored throughout the 21-day time period for the presence of fever to ensure no systemic sepsis occurred. For all groups, the exposed joint was closed with 3-0 vicryl (Ethicon, Inc.) and staples, then Vetbond tissue adhesive (3M) was applied externally.…”

“…The 21-day post-surgery time point was chosen for sample collection as it allowed for the local effects in bone and soft tissue. 31,33,36 Once samples were collected, the animals were euthanized under isoflurane anesthesia with a cardiac puncture, and one cc of Euthasol (Patterson Veterinary) was administered. Blood was collected in BD Vacutainer SST collection tubes (Becton Dickinson Vacutainer), and serum was separated per manufacturer's instructions.…”