Wear particles from joint replacements may result in loosening and periprosthetic osteolysis. Interference with systemic macrophage trafficking to the implant, modulation of macrophage phenotype from M1 to M2, and inhibition of NFκB may mitigate these adverse effects. Joint replacement of the lower extremity is highly successful in alleviating pain, and improving ambulation and function. However, prosthetic byproducts of different materials, in sufficient amounts, may lead to loosening and periprosthetic osteolysis. Debris from polymers (such as polyethylene and PMMA), metals and ceramics are capable of inciting an adverse tissue reaction, which is orchestrated by cells of the monocyte/macrophage lineage. Three experimental approaches have been taken by our group to potentially mitigate the adverse biological sequela of particle disease. These include: 1) interfering with ongoing migration of monocyte/macrophages to the implant site by inhibiting the chemokine system 2) altering the functional activities of local macrophages by converting pro-inflammatory M1 macrophages to an anti-inflammatory pro-tissue healing M2 phenotype and 3) modulating the production and release of pro-inflammatory cytokines, chemokines and other potentially harmful factors by inhibiting the key transcription factor NFκB.Summary
Introduction
