Continuous intramedullary polymer particle infusion using a murine femoral explant model

Abstract

In vitro models are important investigative tools in understanding the biological processes involved in wear-particle-induced chronic inflammation and periprosthetic osteolysis. In the clinical scenario, particles are produced and delivered continuously over extended periods of time. Previously, we quantified the delivery of both polystyrene and polyethylene particles over 2-and 4-week time periods using osmotic pumps and collection tubes. In the present study, we used explanted mice femora in organ culture and showed that continuous intramedullary delivery of submicron-sized polymer particles using osmotic pumps is feasible. Furthermore, infusion of 2.60 3 10 11 particles per mL (intermediate concentration) of ultrahigh molecular weight polyethylene (UHMWPE) for 2 weeks and 8.06 3 10 11 particles per mL (high concentration) UHMWPE for 4 weeks both yielded significantly higher scores for bone loss when compared with controls in which only mouse serum was infused. '

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].…”

The biological response to orthopedic implants for joint replacement. II: Polyethylene, ceramics, PMMA, and the foreign body reaction

“…Pajarinen et al showed that continuous delivery of IL‐4 can modulate macrophage phenotype in vitro from M1 to M2. These results provide promising strategies to mitigate periprosthetic osteolysis by modulating the cytokine microenvironment, and represent avenues for further in vivo studies using clinically relevant models . Figure summarizes the effect of PE particles.…”

“…These results provide promising strategies to mitigate periprosthetic osteolysis by modulating the cytokine microenvironment, and represent avenues for further in vivo studies using clinically relevant models. [25][26][27][28] Figure 1 summarizes the effect of PE particles.…”

Orthopaedic implant failure: aseptic implant loosening–the contribution and future challenges of mouse models in translational research

“…To remedy this, the group of Goodman proposed another model in 2008 [9]. Based on the in vitro and ex vivo validation of particle-release using an Alzet® pump [79,80], Ma et al demonstrated that this model can ensure the constant presence of particles released from a subcutaneous osmotic pump in the femoral intra-medullary cavity, mimicking the human condition [9] (Fig. 4B).…”