A novel mouse model of hindlimb joint contracture with 3D-printed casts.

Stiff joints formed after trauma, surgery or immobilization are frustrating for surgeons, therapists and patients alike. Unfortunately, the study of contracture is limited by available animal model systems, which focus on the utilization of larger mammals and joint trauma. Here we describe a novel mouse-based model system for the generation of joint contracture using 3D-printed clamshell casts. With this model system we are able to generate both reversible and irreversible contractures of the knee and ankle. Four- or 8-month-old female mice were casted for either 2 or 3 weeks before liberation. All groups formed measurable contractures of the knee and ankle. Younger mice immobilized for less time formed reversible contractures of the knee and ankle. We were able to generate irreversible contracture with either longer immobilization time or the utilization of older mice. The contracture formation translated into differences in gait, which were detectable using the DigiGait® analysis system. This novel model system provides a higher throughput, lower cost and more powerful tool in studying the molecular and cellular mechanisms considering the large existing pool of transgenic/knockout murine strains.

3D printed PLA Army-Navy retractors when used as linear retractors yield clinically acceptable tolerances.

BACKGROUND: Modern low-cost 3D printing technologies offer the promise of access to surgical tools in resource scarce areas, however optimal designs for manufacturing have not yet been established. We explore how the optimization of 3D printing parameters when manufacturing polylactic acid filament based Army-Navy retractors vastly increases the strength of retractors, and investigate sources of variability in retractor strength, material cost, printing time, and parameter limitations. METHODS: Standard retractors were printed from various polylactic acid filament spools intra-manufacturer and inter-manufacturer to measure variability in retractor strength. Printing parameters were systematically varied to determine optimum printing parameters. These parameters include retractor width, thickness, infill percentage, infill geometry, perimeter number, and a reinforced joint design. Estimated retractor mass from computer models allows us to estimate material cost. RESULTS: We found statistically significant differences in retractor strength between spools of the same manufacturer and between manufacturers. We determined the true strength optimized retractor to have 30% infill, 3 perimeters, 0.25 in. thickness, 0.75 in. width, and has "Triangle" infill geometry and reinforced joints, failing at more than 15X the threshold for clinically excessive retraction and costs $1.25 USD. CONCLUSIONS: The optimization of 3D printed Army-Navy retractors greatly improve the efficacy of this instrument and expedite the adoption of 3D printing technology in many diverse fields in medicine not necessarily limited to resource poor settings.

Salmonella Mitigates Oxidative Stress and Thrives in the Inflamed Gut by Evading Calprotectin-Mediated Manganese Sequestration.

Neutrophils hinder bacterial growth by a variety of antimicrobial mechanisms, including the production of reactive oxygen species and the secretion of proteins that sequester nutrients essential to microbes. A major player in this process is calprotectin, a host protein that exerts antimicrobial activity by chelating zinc and manganese. Here we show that the intestinal pathogen Salmonella enterica serovar Typhimurium uses specialized metal transporters to evade calprotectin sequestration of manganese, allowing the bacteria to outcompete commensals and thrive in the inflamed gut. The pathogen's ability to acquire manganese in turn promotes function of SodA and KatN, enzymes that use the metal as a cofactor to detoxify reactive oxygen species. This manganese-dependent SodA activity allows the bacteria to evade neutrophil killing mediated by calprotectin and reactive oxygen species. Thus, manganese acquisition enables S. Typhimurium to overcome host antimicrobial defenses and support its competitive growth in the intestine.