BackgroundPost-arthroplasty infections represent a devastating complication of total joint replacement surgery, resulting in multiple reoperations, prolonged antibiotic use, extended disability and worse clinical outcomes. As the number of arthroplasties in the U.S. will exceed 3.8 million surgeries per year by 2030, the number of post-arthroplasty infections is projected to increase to over 266,000 infections annually. The treatment of these infections will exhaust healthcare resources and dramatically increase medical costs.Methodology/Principal FindingsTo evaluate novel preventative therapeutic strategies against post-arthroplasty infections, a mouse model was developed in which a bioluminescent Staphylococcus aureus strain was inoculated into a knee joint containing an orthopaedic implant and advanced in vivo imaging was used to measure the bacterial burden in real-time. Mice inoculated with 5×103 and 5×104 CFUs developed increased bacterial counts with marked swelling of the affected leg, consistent with an acute joint infection. In contrast, mice inoculated with 5×102 CFUs developed a low-grade infection, resembling a more chronic infection. Ex vivo bacterial counts highly correlated with in vivo bioluminescence signals and EGFP-neutrophil fluorescence of LysEGFP mice was used to measure the infection-induced inflammation. Furthermore, biofilm formation on the implants was visualized at 7 and 14 postoperative days by variable-pressure scanning electron microscopy (VP-SEM). Using this model, a minocycline/rifampin-impregnated bioresorbable polymer implant coating was effective in reducing the infection, decreasing inflammation and preventing biofilm formation.Conclusions/SignificanceTaken together, this mouse model may represent an alternative pre-clinical screening tool to evaluate novel in vivo therapeutic strategies before studies in larger animals and in human subjects. Furthermore, the antibiotic-polymer implant coating evaluated in this study was clinically effective, suggesting the potential for this strategy as a therapeutic intervention to combat post-arthroplasty infections.

Aneurysmal bone cysts (ABCs) are benign bone lesions arising predominantly in the pediatric population that can cause local pain, swelling, and pathologic fracture. Primary lesions, which constitute roughly two thirds of all ABCs, are thought to be neoplastic in nature, with one third of ABCs arising secondary to other tumors. Diagnosis is made with various imaging modalities, which exhibit characteristic features such as Bfluid-fluid levels,^although biopsy is critical, as telangiectatic osteosarcoma cannot be excluded based on imaging alone. Currently, the standard of care and most widely employed treatment is intralesional curettage. However, tumor recurrence with curettage alone is common and has driven some to propose a multitude of adjuvants with varying efficacy and risk profiles. Historically, therapies such as en bloc resection or radiation therapy were utilized as an alternative to decrease the recurrence rate, but these therapies imposed high morbidity. As a result, modern techniques now seek to simultaneously reduce morbidity and recurrence, the pursuit of which has produced preliminary study into minimally invasive percutaneous treatments and medical management.

Post-arthroplasty infections are a devastating problem in orthopaedic surgery. While acute infections can be treated with a single stage washout and liner exchange, chronic infections lead to multiple reoperations, prolonged antibiotic courses, extended disability and worse clinical outcomes. Unlike previous mouse models that studied an acute infection, this work aimed to develop a model of a chronic post-arthroplasty infection. To achieve this, a stainless steel implant in the knee joints of mice was inoculated with a bioluminescent S. aureus strain (1×102–1×104 CFUs) and in vivo imaging was used to monitor the bacterial burden for 42 days. Four different S. aureus stains were compared in which the bioluminescent construct was integrated in an antibiotic selection plasmid (ALC2906), the bacterial chromosome (Xen29 and Xen40) or a stable plasmid (Xen36). ALC2906 had increased bioluminescent signals through day 10, after which the signals became undetectable. In contrast, Xen29, Xen40 and Xen36 had increased bioluminescent signals through 42 days with the highest signals observed with Xen36. ALC2906, Xen29 and Xen40 induced significantly more inflammation than Xen36 as measured by in vivo EGFP-neutrophil florescence of LysEGFP mice. All four strains induced comparable biofilm formation as determined by variable-pressure scanning electron microscopy. Using a titanium implant, Xen36 had higher in vivo bioluminescence signals than Xen40 but had similar biofilm formation and adherent bacteria. In conclusion, Xen29, Xen40 and especially Xen36, which had stable bioluminescence constructs, are feasible for long-term in vivo monitoring of bacterial burden and biofilm formation to study chronic post-arthroplasty infections and potential antimicrobial interventions.