Particulate wear debris from the UHMWPE component of implant prostheses typically causes inflammatory cascades leading to bone resorption and prosthesis loosening. Aseptic loosening is the leading cause of joint replacement failure. Green et al. have shown that the most biologically active polyethylene wear particles are in size range 0.3–10 micrometer, determined by filtration and Scanning Electron Microscopy. A new methodology based on radioisotope tracing is investigated which promises aseptic loosening is the leading cause of joint replacement failureto be more sensitive and may allow the characterization of wear debris shedding on the nanometer-scale. A constant force knee simulator has been designed and constructed at the University of New South Wales, to generate reproducible wear patterns. Atomic Force Microscopy is used to measure the wear particle dimensions. The constant axial force can be adjusted over a range of 0–1000 N, and flexion angles of 24°, 38°, 51° and 66° can be set. The UHMWPE wear surface is articulated at a rate of 1 cycle per second. It has been found that the simulator operates reliably over up to 2×10^6 cycles at various loads and flexion angles, and that wear debris can successfully be removed from the lubricant. For a walking cycle simulation, a wear rate of the order of 86 mg/10^6 cycles was measured using distilled water as lubricant. The debris particulates generated from the simulation have been characterized with Atomic Force Microscopy. In the nanometer range two characteristic types, clumps and fibrils, may be distinguished. A constant force knee simulator has been shown to operate reliably over up to 2×10^6 cycles at various loads and flexion angles, and that wear debris particulates can be obtained. It has also been shown that atomic force microscopy is well suited to characterize nanometre size UHMWPE particles. In parallel, the wear debris generated from the experiments is being tested for their bioirritant characteristics on osteoblast cells (in the TORU laboratory at the John Curtin School of Medical Research at ANU).