Shoulder hemiarthroplasty is a minimally invasive procedure that requires less surgical time and better preserves healthy cartilage compared to total arthroplasties. However, patient outcomes are not always conclusive, and this is because metal humeral heads induce cartilage erosion and the release of local tissue metal toxicity. The recently developed InSpyre (Tornier-Wright) consists of a graphite substrate coated with pyrolytic carbon (PyC). Due to its specific surface characteristics and previous medical applications (heart valves and joint implants), PyC could suppress metal toxicity and limit tissue wear due to its Young's modulus close to that of bone (30 MPa vs. 50MPa respectively). In a previous study, we found that phospholipids adsorbed 3 times more onto PyC after friction against living cartilage compared to cobalt alloy. As PLs are known to be involved in lubrication, this suggests a reduction in friction against the tissue by the affinity of PyC to PLs. However, it is not known how PLs affect the electrochemical resistance of PyC and whether friction is necessary to promote PLs adsorption. This study aims to determine whether the physicochemical structure of PLs affects the reactivity of PyC by comparing its electrochemical properties in cell culture medium without, with PLs vesicles, and with disrupted PLs vesicles. A custom electrochemical setup based on a Petri dish with pyrolytic carbon disks was used. The electrolyte is a synthetic synovial fluid based on DMEM/F12 (cell culture medium, CCM) with or without hyaluronic acid (HA)-phospholipid vesicles (PLs). These vesicles represent synthetic surface-active phospholipids, conferring the lubricating capacity of synovial fluid. Characterization of the biomaterial/electrolyte interface and the adsorption process was performed by EIS measurements performed after 10 and 60min of exposure. Measurements were performed from 1mHz up to 105 Hz, at 9 cycles/dec with an ac amplitude of ± 10mV. Tests were performed in an incubator (95% humidity, 5% CO2, 37°C). Analogous electrochemical tests with a surfactant (Triton X-100) were performed to simulate disrupted phospholipid vesicles, to reproduce the physicochemical modification of synovial fluid of joint disease. Statistical differences between solutions were performed using a nonparametric Kruskal-Wallis test (SPSS Inc, Chicago, IL). The significance level was set at P<0.05. The OCP of PyC in DMEM with and without PLS is decreasing reaching an average potential of 51 and 83 mV/AgAgCl, respectively (Fig 1A, B). This negative evolution of the OCP of PyC indicates the formation of a non-protective layer on the biomaterial surface. The lower OCP in the presence of PLs vesicles suggests a surface modification due to PLs adsorption. By adding the surfactant to the solution, the OCP started at a lower potential value (14 mV/AgAgCl) and increased during a 1h exposure (Fig 1 C). The addition of PLs produced a change on the electrochemical reactions (taking place on the biomaterial/body fluid interface, cathodic and anodic reaction) at the OCP. The EIS plots show a typical passive state shape characterized by high impedance values with non-ideal capacitive behavior. The EIS results were fitted with a Randles circuit including a phase angle element (CPE) to replace the capacitor for the non-ideal behavior of the capacitive elements due to different physical phenomena. It was found that the addition of PLs strongly increases the resistance of PyC after a one-hour polarization (Fig 1D). The presence of PLs vesicles resulted in a greater increase in charge transfer resistance compared with DMEM under identical conditions. These changes in charge transfer resistance and capacity are attributed to the formation of a phospholipid layer on the PyC surface. Addition of surfactant (Triton X100) resulted in similar capacitance and charge transfer resistance to DMEM after 1 h of exposure, suggesting that the disrupted vesicles do not adsorb or protect PyC (Fig 1D,E). Surface analysis and observations are required to confirm these preliminary results. This study reveals that the physicochemical structure of synthetic synovial fluid impacts the chemical resistance of PyC, conferring better protection with the addition of PLs vesicles. Joint disease was simulated by disrupting PLs vesicles with the introduction of a surfactant. It reveals the loss of protective behavior, emphasizing that concentration is not the main factor in the chemical resistance of biomaterials. The affinity of PLs with the current main metallic orthopedic implants, Cobalt and Titanium alloys, is an ongoing project to define how phospholipid vesicles impact their corrosion resistance. Figure 1