The aim of the present research was focused on the study of the effect of replacing vanadium by niobium and iron on the tribological behavior of Hot Isostatic Pressed (HIPed) titanium alloy (Ti-6Al-4V) biomaterial, using a ball-on-disk type Oscillating tribometer, under wet conditions using physiological solution conditions (Ringer solution) in accordance with the ASTMG 99, ISO 7148-1:2012, and ASTM G 133–95 standards. The tests were carried out under a normal load of 6 N, with an AISI 52100 grade steel ball as a counter face. The morphological changes and structural evolution of the nanoparticle powders using different milling times (2, 6, 12 and 18 h) were studied. The morphological characterization indicated that the particle and crystallite size continuously decreases with increasing milling time to reach the lowest value of 4 nm at 18 hours milling. The friction coefficient and wear rate were lower in the samples milled at 18 h (0.226, 0.297 and 0.423) and (0.66 x10-2, 0.87x10-2 and 1.51x10-2 µm3.N-1.µm-1) for Ti-6Al-4Fe, Ti-6Al-4Nb and Ti-6Al-4V, respectively. This improvement in friction and wear resistance is attributed to the grain refinement at 18 hour milling. The Ti-6Al-4Fe samples showed good tribological performance for all milling times

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