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

Abstract

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.

Toll‐like receptors‐2 and 4 are overexpressed in an experimental model of particle‐induced osteolysis

“…Other limitations of our current study include the use of a short-term, single dose animal model that simulates the complex biological picture of particle disease in humans in which prosthetic implants are subjected to waves of cyclic fluid pressure and continuous delivery of particles over many years 47,51,52 . Nevertheless, the animal model did reveal TLR activation patterns that are remarkably consistent with those that have been seen in human tissues harvested from failed joint revision surgeries.…”

Continuous Infusion of UHMWPE Particles Induces Increased Bone Macrophages and Osteolysis

“…We strictly followed Stanford University's guidelines for the care and use of laboratory animals. The murine continuous femoral intramedullary infusion model used in this study was modified from a previously described rat model [22] and validated by successfully pumping UHMWPE and blue polystyrene particles into murine femoral medullary canals [25,31,32].…”

“…Instead of pumping particles into the knee and inserting a solid wire into the femoral medullary canal, we modified the rat model of Kim et al [18,22] by implanting a hollow titanium rod in the distal part of the femur and pumping particles into the femoral bone marrow cavity directly. In this modified mouse model, polyethylene particles were infused continuously into the femur through an osmotic pump to simulate the clinical scenario more closely [25,26,31,32].…”

Exogenous MC3T3 Preosteoblasts Migrate Systemically and Mitigate the Adverse Effects of Wear Particles

“…The procedure was adapted from a previously described rat model 31 and has been validated. 32,33 The animals were anesthetized using 3%-5% isoflurane in 100% oxygen and kept on a warm, sterile small animal surgery station. A medial parapatellar incision was made and the medullary cavity was exposed via the intercondylar notch of the distal left femur.…”