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Figure 1: Schematic representation of periprosthetic loosening and osteolysis. Implant-derived wear debris induces an early inflammatory response from the resident or infiltrating macrophages in the periprosthetic tissue. Small particles are phagocytosed, whereas the larger induce fusion of macrophages and giant cell formation. Activated macrophages release proinflammatory cytokines, chemokines, and enzymes that recruit multiple cell types within periprosthetic tissue, which are further activated by the particles resulting in sustained inflammation, increased secretion of cytokines/chemokines/osteoclastogenic factors/MMPs/TIMPs, and osteolysis.