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We evaluated the interface membranes surrounding three total shoulder prostheses that had been removed because of progressive aseptic loosening associated with osteolysis. The mean time between the uncomplicated initial arthroplasty and the revision procedure was twelve years (10.5, 10.5, and 16.0 years). Membranes from around both the humeral and the glenoid component were obtained from all three shoulders and were studied histologically to determine the biological response involved in the development of aseptic loosening. For the purpose of comparison, periprosthetic tissue was also obtained from the sites of four failed total hip prostheses that were associated with osteolysis.Polyethylene particles were retrieved with an enzymatic digestion technique that involved the use of papain. Raman vibrational spectroscopy verified that the particles were ultra-high molecular weight polyethylene. The particles were isolated from the tissue, and a computerized image-analysis system characterized 582 of them in terms of size and morphology. Each particle was defined with the use of six shape descriptors: equivalent circle diameter, roundness, form factor, aspect ratio, elongation, and outline fractal dimension. The particles from the hips had a mean equivalent circle diameter (and standard error of the mean) of 0.62 ± 0.03 micrometer, were predominantly globular in shape, and had low mean values for aspect ratio (1.46 ± 0.02) and elongation (1.85 ± 0.03) and relatively high values for roundness (0.74 ± 0.01) and form factor (0.87 ± 0.01). In contrast, the particles from the shoulders had a mean equivalent circle diameter of 1.04 ± 0.03 micrometers. In addition, they had relatively high values for aspect ratio (2.36 ± 0.07) and elongation (4.96 ± 0.23) and correspondingly low values for roundness (0.54 ± 0.01) and form factor (0.67 ± 0.01), indicating that they were more fibrillar in shape. The particles from the shoulders and those from the hips were significantly different (p < 0.0001) with respect to all of the descriptors except outline fractal dimension. The particles from the shoulders, in general, were larger and more fibrillar than the particles from the hips.CLINICAL RELEVANCE: This study demonstrated that particles generated by the wear of the ultra-high molecular weight polyethylene of total shoulder prostheses can be associated with clinically important osteolysis, with a pathogenesis that is similar to that of aseptic loosening after total hip replacement. The polyethylene wear debris obtained from the membranes around three failed total shoulder prostheses was strikingly different in terms of morphology than the wear debris obtained from the tissue around failed total hip prostheses; this finding suggests that the type of joint markedly influences the wear mechanism and the nature of the resulting debris.