The purpose of this study is to develop and validate a novel murine model of continuous particle infusion and an intramedullarv orthopaedic implant in order to understand fundamental biological processes involved in particle induced periprosthetic bone loss (osteolvsis).
Specific aim #1. To optimize the number of polystyrene blue microspheres (PS) or clinically relevant polyethylene particles (PE) 0.5 urn in diameter, in different concentrations, delivered by an infusion pump connected to a hollow CP titanium rod and tubing over a 4-week period.
Specific aim #2. To develop and optimize an organ culture model using continuous infusion of PS or PE particles into an explanted mouse femur containing a hollow titanium rod connected to an infusion pump and tubing over a 4-week period.
Specific aim #3. To develop, optimize and validate an in vivo model employing continuous infusion of polyethylene particles into the mouse femur containing a hollow titanium intramedullary rod connected to an infusion pump. Three novel models will be introduced. In the first model, different concentrations of 0.5 urn PS or PE particles will be continuously infused into a gathering vessel over a 4-week period using an Alzet infusion pump, tubing and 10 mm long 23 gauge hollow titanium rod. In the second model, an organ culture system will be maintained, consisting of PS or PE particles continuously infused into the explanted murine femur containing a hollow rod connected to an infusion pump. The number of infused particles will be assessed by quantifying the residual particles in the tubing, in the gathering vessel and in the explanted femur using SEM and histomorphometry at 2-weekly intervals. The in vivo experiment will develop and validate a murine model in which clinically relevant PE particles are continuously infused into the femur containing a 10 mm long 23 gauge hollowed titanium rod using an infusion pump and tubing. The harvested femora will be assessed using radiographs, micro CT and histomorphometric analysis. The above experiments will facilitate future research on a) the biological mechanisms of periprosthetic bone loss (osteolysis) using wild type and genetically altered murine species b) the biological effects of novel materials with different particle characteristics and c) potential pharmacologic interventions to mitigate periprosthetic bone loss due to wear debris.
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