Validation and quantification of an in vitro model of continuous infusion of submicron-sized particles

Wear particles produced from total joint replacements have been shown to stimulate a foreign body and chronic inflammatory reaction that results in periprosthetic osteolysis. Most animal models that simulate these events have used a single injection of particles, which is not representative of the clinical scenario, in which particles are continuously generated. The goal of this study was to evaluate the feasibility of an osmotic pump for the continuous delivery of clinically relevant submicron-sized particles over an extended period of time. Blue-dyed polystyrene particles and retrieved ultra-high molecular weight polyethylene (UHMWPE) particles, both suspended in mouse serum, were loaded into an Alzet mini-osmotic pump. Pumps were attached to vinyl tubing that ended with hollow titanium rods, simulating a metal implant, which was suspended in a collection vessel. The number of particles collected was evaluated over 2- and 4-week time periods. Delivery of both the polystyrene and UHMWPE particles was feasible over pump concentrations of 10(9) to 10(11) particles per pump. Furthermore, delivery efficiency of polystyrene particles decreased with increasing initial particle concentration, whereas delivery efficiency of UHMWPE particles increased slightly with increasing initial particle concentration. For UHMWPE, approximately one-third of the particles in the pump were collected at 4 weeks. This in vitro study has quantified the efficiency of a unique particle pumping system that may be used in future in vivo investigations to develop a murine model of continuous particle infusion.