Cytotoxicity and MMP-9 activation induced in human mononuclear cells by UHMWPE oxidation

Ultra high molecular weight polyethylene (UHMWPE) used in orthopedic prosthesis can be oxidized during sterilization processes such as gamma-ray irradiation. Oxidation alters UHMWPE structure and mechanical properties and it has been suggested that this alteration is the first step in the loosening process. Direct effects of UHMWPE oxidation on the cellular and tissue response to the implant have not been previously investigated. We used heat-oxidized UHMWPE, whose oxidative state is comparable to the one induced in gamma-ray irradiated polymer. in order to observe the peripheral blood mononuclear cells (PBMCs) behavior after 24 and 48 h exposure to the oxidized and non-oxidized polymers. Flow cytometric analysis showed a cytotoxic effect of oxidized UHMWPE after 48 h compared with the control samples. Moreover, gelatin zymography of PBMCs conditioned media showed a strong increase in MMP-9 (gelatinase B) release and activation in oxidized UHMWPE samples. This first evidence of a direct effect of the UHMWPE oxidative status on the cellular behavior suggests that oxidation alters not only the UHMWPE physical-mechanical properties. but it can also be responsible for altered tissue response.