The wear and biological activity of antioxidant UHMWPE for use in total hip replacements

Total hip replacements (THR) are considered one of the most successful surgical procedures in medicine; eliminating pain and restoring mobility following conditions such as osteoarthritis. The majority of THR implants have a metal femoral head articulating against an UHMWPE acetabular cup, however, UHMWPE wear debris is generated over time, and this wear debris stimulates an osteolytic immune response around the implant, leading to aseptic loosening and eventually failure of the prosthesis. Highly crosslinked UHMWPE has been developed with excellent wear resistance, however the generation of free radicals following gamma irradiation can lead to oxidation of the UHMWPE material, reducing the mechanical properties of UHMWPE. In addition, oxidation through lipid absorption in vivo has been shown to occur, independent of irradiation-generated radical species. This led to the development of antioxidant UHMWPE, with vitamin E enhanced highly crosslinked UHMWPE introduced clinically in the hip in 2007, and hindered phenol enhanced highly crosslinked UHMWPE introduced clinically in the knee in 2012. Using a six station pin-on-plate wear simulator under kinematics associated with the hip joint, it was shown that the introduction of a vitamin E or hindered phenol antioxidant to UHMWPE had no significant effect on the wear factor. The addition of moderate (5MRad) and high (10MRad) levels of crosslinking significantly reduced the wear factor of UHMWPE, both with and without vitamin E. Comparing both these highly crosslinked antioxidant UHMWPE materials to virgin UHMWPE, there was no significant difference in the wear particle size distribution observed, indicating the addition of high levels of crosslinking and antioxidant enhancement had no significant effect on the size distribution of UHMWPE wear debris. A large volume of clinically relevant sterile wear debris was generated in 25% bovine serum (v/v) to then incubate with peripheral blood mononuclear cells (PBMNCs) isolated from healthy human donors. Testing both the vitamin E enhanced and hindered phenol enhanced UHMWPE, along with non-antioxidant highly crosslinked UHMWPE wear debris, it was shown that vitamin E enhanced highly crosslinked UHMWPE caused significantly lower levels of TNF-α release from PBMNCs compared to the non-antioxidant highly crosslinked UHMWPE. This reduction in TNF-α release was also observed in hindered phenol enhanced highly crosslinked UHMWPE, indicating the presence of vitamin E or hindered phenol antioxidants caused a reduction in the release of the osteolytic cytokine TNF-α. Stimulation of significant levels of cytokine release from PBMNCs was only achieved in 3D culture at a wear debris concentration of >200 μm³. Vitamin E enhanced highly crosslinked UHMWPE wear debris was also shown to stimulate lower levels of reactive oxygen species production in PBMNCs, compared to highly crosslinked UHMWPE wear debris. This indicated that the presence of vitamin E in highly crosslinked UHMPWE wear debris led to intracellular antioxidant activity, reducing the oxidative stress following treatment with wear debris. These results showed clear evidence that enhancement of highly crosslinked UHMWPE with a vitamin E or hindered phenol antioxidant has no significant effect on the wear resistance of the material, however the antioxidant and anti-inflammatory properties of these materials lead to lower levels of TNF-α and reactive oxygen species production in macrophages, potentially reducing the levels of osteolysis around the implant.