Andrew Neils

A new mechanism of oxidation in ultrahigh molecular weight polyethylene caused by squalene absorption

Although synovial fluid lipids were found to absorb in ultrahigh molecular weight polyethylene (UHMWPE) total joint implants in vivo, their effect on the oxidation of the polymer was not known. Current understanding of the oxidation and oxidative stability of UHMWPE joint implants is focused on the presence or elimination of radiation-induced free radicals, which are long-lived and can react with oxygen over the long term. Recently, we found unexplained oxidation in irradiated and melted UHMWPE components that were exposed to bodily fluids then stored on the shelf despite being free of detectable free radicals at the time of implantation. Thus, we hypothesized that lipids absorbed from the synovial fluid in vivo could initiate and accelerate oxidation of UHMWPE even in the absence of detectable residual free radicals. We found that squalene, a precursor in cholesterol synthesis and a synovial fluid lipid with unsaturated bonds, accelerated oxidation in irradiated and melted UHMWPE under in vitro accelerated aging conditions. This result represents a paradigm shift in our understanding of oxidative stability of UHMWPE and prompts further investigation of in vivo oxidation mechanisms as well as the development of relevant in vitro aging models.

Increasing irradiation temperature maximizes vitamin E grafting and wear resistance of ultrahigh molecular weight polyethylene

Vitamin E stabilization of radiation crosslinked ultrahigh molecular weight polyethylene (UHMWPE) for total joint implants can be done by blending of UHMWPE resin powder with vitamin E, followed by consolidation and irradiation of the blend. It is well known that vitamin E prevents crosslinking in UHMWPE during ionizing radiation. We hypothesized that there would also be a significant amount of grafting of vitamin E onto UHMWPE during irradiation. Spectroscopic analysis of radiation crosslinked vitamin E-blended UHMWPE before and after extraction with boiling hexane showed vitamin E grafting in up to 30% of the blended vitamin E. Grafting increased with irradiation temperature. We also discovered that increasing irradiation temperature resulted in better preservation of active vitamin E in the polymer and increased crosslinking efficiency of UHMWPE. As a result, warm-irradiated vitamin E-blended UHMWPEs had significantly less wear than those irradiated at ambient temperature. It may be desirable to graft vitamin E on UHMWPE to decrease the possibility of elution and increase long-term stability. Warm irradiation of vitamin E blends may present an advantage in increasing vitamin E potency, as well as decreasing the wear of UHMWPE, which is crucial in decreasing the incidence of periprosthetic osteolysis in total joint replacement patients.

Effects of simulated oxidation on the in vitro wear and mechanical properties of irradiated and melted highly crosslinked UHMWPE

Radiation crosslinked ultrahigh molecular weight polyethylene (UHMWPE) have reduced the wear rate of the bearing surface in total joint arthroplasty and the incidence of peri-prosthetic bone loss due to wear particles. The oxidation potential afforded to the material by the trapped residual free radicals after irradiation was addressed in first generation crosslinked UHMWPEs by using thermal treatments such as annealing or melting after irradiation. Postirradiation melted crosslinked UHMWPE did not contain detectable free radicals at the time of implantation and was expected to be resistant against oxidation for the lifetime of the implants. Recent analyses of long-term retrievals showed it was possible for irradiated and melted UHMWPEs to oxidize in vivo but studies on the effects of oxidation on these materials have been limited. In this study, we determined the effects of in vitro aging on the wear and mechanical properties of irradiated and melted UHMWPE as a function of radiation dose and found that even small amount of oxidation (oxidation index of 0.1) can have detrimental effects on its mechanical properties. There was a gradual increase in the wear rate below an oxidation index of 1 and a drastic increase thereafter. Therefore, it was shown in a simulated environment that oxidation can have detrimental effects to the clinically relevant properties of irradiated and melted UHMWPEs.

Surface cross-linked UHMWPE can enable the use of larger femoral heads in total joints

Limiting cross‐linking to the articular surfaces of ultrahigh molecular weight polyethylene (UHMWPE) to increase wear resistance while preventing detrimental effects of cross‐linking on mechanical strength has been a desirable goal. A surface cross‐linked UHMWPE can be achieved by blending UHMWPE with a free radical scavenger, such as vitamin E, consolidating the blend into an implant shape, extracting the vitamin E from the surface, and radiation cross‐linking the surface extracted blend. This process results in high cross‐link density in the vitamin E‐depleted surface region because vitamin E hinders cross‐linking during irradiation. In this study, we described the properties of successful extraction media and the manipulation of the wear and mechanical properties of extracted, irradiated blends. We showed that these formulations could have similar wear and significantly improved mechanical properties compared to currently available highly cross‐linked UHMWPEs. We believe that these materials can enable thinner implant forms and more anatomical designs in joint arthroplasty and may provide a feasible alternative to metal‐on‐metal implants.

High vitamin E content, impact resistant UHMWPE blend without loss of wear resistance

Antioxidant stabilization of radiation cross-linked ultrahigh molecular weight polyethylene (UHMWPE) has been introduced to improve the oxidative stability of total joint implant bearing surfaces. Blending of antioxidants (most commonly vitamin E) with UHMWPE resin powder followed by consolidation and uniform radiation cross-linking is currently available for use in both total hips and total knees. It was previously shown that the fatigue resistance of vitamin E-blended and irradiated UHMWPEs could be further improved by spatially manipulating the vitamin E concentration throughout the implant and limiting cross-linking to the surface of the implant where it is necessary for wear resistance. This was possible by designing a low concentration of vitamin E on the surface and higher concentration in the bulk of the implant because cross-linking is hindered in UHMWPE as a function of increasing vitamin E concentration. In this study, we hypothesized that such a surface cross-linked UHMWPE with low wear rate and high fatigue strength could be obtained by limiting the penetration of radiation into UHMWPE with uniform vitamin E concentration. Our hypothesis tested positive; we were able to obtain control of the surface cross-linked region by manipulating the energy of the irradiation, resulting in extremely low wear, and high impact strength. In addition, we discussed alternatives of improving the oxidation resistance of such a material by using additional vitamin E reservoirs. These results are significant because this material may allow increased use of antioxidant-stabilized, cross-linked UHMWPEs in high stress applications and in more active patients.

Peroxide cross-linked UHMWPE blended with vitamin E.

Radiation crosslinked ultrahigh molecular weight polyethylene (UHMWPE) is the bearing surface material most commonly used in total joint arthroplasty because of its excellent wear resistance. Crosslinking agents such as peroxides can also effectively increase wear resistance but peroxide crosslinked UHMWPE has low oxidative stability. We hypothesized that the addition of an antioxidant to peroxide crosslinked UHMWPE could improve its oxidation resistance and result in mechanical, tribological, and oxidative properties equivalent to currently utilized radiation crosslinked UHMWPEs. Various vitamin E (0.1-1.0 wt % and peroxide concentration (0.5-1.5 wt %) combinations were studied to investigate changes in crosslink density, wear rate, mechanical properties, and oxidative stability in comparison to radiation crosslinked UHMWPE. Peroxide crosslinking was more efficient as compared to radiation crosslinking in the presence of vitamin E with the former resulting in lower wear rate with vitamin E concentrations above 0.3 wt %. The tensile mechanical properties were comparable to and the impact strength was higher than those of the clinically relevant radiation crosslinked controls. We also determined that gamma sterilization of peroxide crosslinked vitamin E blends improved wear resistance further. In summary, peroxide crosslinking of vitamin E-blended UHMWPE may provide a feasible and economical alternative to radiation for achieving clinically relevant properties for total joint implants using UHMWPE.

The effect of an additional phosphite stabilizer on the properties of radiation cross‐linked vitamin E blends of UHMWPE

Antioxidant stabilization of radiation cross‐linked ultrahigh molecular weight polyethylene (UHMWPE) has been introduced to improve the oxidative stability of total joint implant bearing surfaces. Blending of an antioxidant with UHMWPE resin powder followed by consolidation and radiation cross‐linking has been cleared by the FDA for use in both total hips and total knees for designs incorporating two antioxidants, namely vitamin E and Covernox™ (a medical grade version of Irganox™ 1010). The antioxidants in the polymer are expected to protect the polymer during consolidation, during radiation cross‐linking, on the shelf before implantation, and in vivo after implantation. To maximize the protection of the polymer afforded by the antioxidant in vivo, a novel approach may be the use of multiple antioxidants, especially to protect the primary antioxidant for a longer period of time. We hypothesized that the addition of a phosphite stabilizer (Irgafos 168™) commonly used in conjunction with hindered phenolic antioxidants in polymer processing could improve the oxidative stability of radiation cross‐linked blends of vitamin E. To test our hypothesis, we prepared UHMWPE blends with 0.05 wt% Irgafos and 0.05 wt% vitamin E and compared its cross‐link density, wear resistance, tensile properties, and impact strength to control blends containing only vitamin E. Our hypothesis was not supported; the cross‐link density of UHMWPE was significantly decreased by the additive without additional benefit to oxidative stability. To our knowledge, this was the first attempt at using multiple stabilizers in medical grade UHMWPE.