Do total hip arthroplasty polyethylene liners without free radicals oxidize in vivo or ex vivo?

Crosslinking substantially reduces the wear of ultra-high molecular weight polyethylene (UHMWPE) used in total hip arthroplasty (THA) but some reports have indicated that first generation liners manufactured without antioxidants may be vulnerable to in vivo oxidation. This study evaluated maximum oxidation using Fourier transform infrared spectroscopy per ASTM F2102-06ε1 and linear head penetration using a coordinate measuring machine among 66 revision-retrieved THA components with in vivo durations ranging from 0.02 to 24.6 years. These included 30 liners crosslinked with 5 Mrad of gamma radiation and then melted, 13 non-crosslinked, never-irradiated liners sterilized with gas plasma and 23 non-crosslinked, never-irradiated liners sterilized with ethylene oxide. All liners were vacuum-sealed and stored at -20°C prior to analysis with the exception of three retrievals of each material type that were stored in air for 9.9 to 21.5 years. All 57 vacuum-sealed and frozen retrievals demonstrated good oxidative stability with maximum oxidation indices (OIs) less than 1.0 and 75% (43/57) of these liners had maximum OIs less than 0.1. Linear penetration measurements were lower in the crosslinked liners compared to non-crosslinked retrievals. Although instances of oxidation and embrittlement were found after ex vivo storage in air among liners that did not have free radicals at the time of implantation, in vivo oxidation does not appear to be a clinical concern through the first decade of service for crosslinked liners and at up to 25 years after surgery for non-crosslinked liners.

In-vitro oxidation model for UHMWPE incorporating synovial fluid lipids.

Post-irradiation melting of ultra-high molecular weight polyethylene (UHMWPE) reduced the oxidation potential of UHMWPE in vivo. After mid-term (5-10 years) use in vivo, there is detectable oxidation in irradiated and melted joint implant retrievals. The absorption of the synovial fluid lipid squalene was identified as a possible factor initiating oxidation. We investigated the role of lipids in UHMWPE oxidation by asking: (1) Do other synovial fluid lipids initiate oxidation in irradiated and melted UHMWPE?; (2) What is the effect of the absorption of multiple lipids on UHMWPE oxidation?; (3) How does lipid-initiated oxidation in vitro compare to what is observed in long-term retrievals? We diffused emulsified single and mixed lipids into irradiated and melted UHMWPE and accelerated aged them. We analyzed the oxidation in these samples and in four long-term highly crosslinked, irradiated, and melted Longevity™ UHMWPE liner retrievals (in vivo for up to 190 months) using Fourier Transform Infrared Spectroscopy (FTIR). We showed that lipids other than squalene could initiate oxidation in UHMWPE and that the types of absorbed lipids determined the amount of resultant oxidation. Although mixed lipids doping and accelerated aging reproduced the average and maximum oxidation values and oxidation products observed in vivo, the oxidation depth profile and its effect on cross-link density was different. One reason for this was the variability of oxidation in retrievals, suggesting additional factors contributing to oxidation. The understanding of oxidative processes in vivo and the development of clinically relevant in vitro protocols to evaluate implant materials is crucial for their long-term performance. © 2018 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:1833-1839, 2018.

Analysis of Dual Mobility Liner Rim Damage Using Retrieved Components and Cadaver Models.

BACKGROUND: The objective of this study was to assess the retentive rim of retrieved dual mobility liners for visible evidence of deformation from femoral neck contact and to use cadaver models to determine if anterior soft tissue impingement could contribute to such deformation. METHODS: Fifteen surgically retrieved polyethylene liners were assessed for evidence of rim deformation. The average time in vivo was 31.4 months, and all patients were revised for reasons other than intraprosthetic dislocation. Liner interaction with the iliopsoas was studied visually and with fluoroscopy in cadaver specimens using a dual mobility system different than the retrieval study. For fluoroscopic visualization, a metal wire was sutured to the iliopsoas and wires were also embedded into grooves on the outer surface of the liner and the inner head. RESULTS: All retrievals showed evidence of femoral neck contact. The cadaver experiments showed that liner motion was impeded by impingement with the iliopsoas tendon in low flexion angles. When observing the hip during maximum hyperextension, 0°, 15°, and 30° of flexion, there was noticeable tenting of the iliopsoas caused by impingement with the liner. CONCLUSION: Liner rim deformation resulting from contact with the femoral neck likely begins during early in vivo function. The presence of deformation is indicative of a mechanism inhibiting mobility of the liner. The cadaver studies showed that liner motion could be impeded because of its impingement with the iliopsoas. Such soft tissue impingement may be one mechanism by which liner motion is routinely inhibited, which can result in load transfer from the neck to the rim.

Investigation of surgically retrieved, vitamin E-stabilized, crosslinked UHMWPE implants after short-term in vivo service.

BACKGROUND: Antioxidant stabilized highly crosslinked ultra-high molecular weight polyethylene (UHMWPE) components have been in clinical use since 2008. In vitro testing has shown excellent oxidation resistance, wear resistance, mechanical properties, and fatigue strength. In this study, we analyzed surgically retrieved components to investigate in vivo behavior and changes in the material. METHODS: Fifteen surgically retrieved, vitamin E-stabilized, and radiation crosslinked UHMWPE components were analyzed to determine their oxidative stability, extent of lipid absorption in vivo, free radical content, hydroperoxide index, and extent of visible wear damage after in vivo service (0.1-36.6 months). RESULTS: Retrievals showed no significant carbonyls at the time of surgical removal, while free radical content was observed to decay with increasing in vivo duration. There was no increase in hydroperoxide index. Lipid penetration increased with time. Ex vivo oxidation was not observed after 18 months of aging in air at room temperature. CONCLUSIONS: The free-radical scavenging activity of the vitamin E appears to successfully prevent both in vivo and ex vivo oxidation for short durations, while reducing free radical content overall. Without an increase in hydroperoxides, the oxidation cascade initiated by radiation-induced and lipid-derived free radicals appears to have been inhibited. Further investigation is required with longer duration implants. © 2015 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 104B: 1132-1140, 2016.

In Vivo Oxidative Stability Changes of Highly Cross-Linked Polyethylene Bearings: An Ex Vivo Investigation.

The development of highly cross-linked UHMWPEs focused on stabilizing radiation-induced free radicals as the sole precursor to oxidative degradation. However, secondary in vivo oxidation mechanisms have been discovered. After a preliminary post-operative analysis, we subjected highly cross-linked retrievals with 1-4 years in vivo durations and never-implanted controls to accelerated aging to predict the extent to which their oxidative stability was compromised in vivo. Lipid absorption, oxidation, and hydroperoxides were measured using infrared spectroscopy. Gravimetric swelling was used to measure cross-link density. After aging, all retrievals, except vitamin E-stabilized components, regardless of initial lipid levels or oxidation, showed significant oxidative degradation, demonstrated by subsurface oxidative peaks, increased hydroperoxides and decreased cross-link density, compared to their post-operative material properties and never-implanted counterparts, confirming oxidative stability changes.

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.

Comparative oxidative stability of α-tocopherol blended and diffused UHMWPEs at 3 years of real-time aging.

Vitamin E (α-tocopherol) is a free-radical stabilizing antioxidant used to maintain oxidative stability in radiation cross-linked ultra-high molecular weight polyethylene (UHMWPE) used in total joint replacements. We investigated the oxidative resistance of vitamin E-stabilized UHMWPE in (i) postirradiation vitamin E-diffused UHMWPE, (ii) vitamin E blended and irradiated UHMWPE, and (iii) unstabilized, irradiated UHMWPE after accelerated aging and real-time aging in an aqueous environment at 40°C for 36 months. Unstabilized samples exhibited substantial oxidation throughout the surface and bulk with both types of aging. While vitamin E-stabilized, radiation cross-linked UHMWPEs were all superior to unstabilized samples, irradiated blends showed surface oxidation and subsurface oxidation potential beginning at ten months in real-time aging. In contrast, postirradiation vitamin E-diffused UHMWPEs showed no detectable oxidation and no increase in oxidation potential despite elution of some vitamin E. We also showed that current thermal accelerated aging methods were unable to differentiate among the oxidative stability of vitamin E-stabilized, radiation cross-linked UHMWPEs prepared by different processes.

Ex vivo stability loss of irradiated and melted ultra-high molecular weight polyethylene.

BACKGROUND: Radiation crosslinking reduces wear of ultra-high molecular weight polyethylene (UHMWPE), and subsequent annealing or melting increases oxidative stability. Little is known about the oxidative stability of polyethylene total joint components after in vivo service and subsequent shelf storage in air. METHODS: We analyzed thirty-four surgically retrieved, radiation crosslinked acetabular liners to determine their oxidative stability after in vivo service (range, 0.5 to 84.0 months). Oxidation was determined at the time of explantation. After shelf storage in air (range, 7.0 to 72.0 months), oxidation, crosslink density, and thermal properties were determined. Oxidation of one control liner that was shelf-aged in air (for eighty-four months) was also determined. RESULTS: At the time of explantation, all components showed minimal oxidation; however, oxidation levels increased during shelf storage, with a concomitant decrease in crosslink density and increase in crystallinity. Increasing oxidation, increasing crystallinity, and decreasing crosslink density correlated with the duration of ex vivo storage. The shelf-aged control liner showed no detectable oxidation. CONCLUSIONS: The oxidation and loss of crosslink density of the irradiated and melted UHMWPE was surprising. Two potential mechanisms that might alter the oxidative stability of UHMWPE in vivo are cyclic loading and absorption of lipids. Both of these mechanisms can generate new free radicals in UHMWPE and can initiate and propagate its oxidation.

A surface crosslinked UHMWPE stabilized by vitamin E with low wear and high fatigue strength.

Wear particle-induced periprosthetic osteolysis has been a clinical problem driving the development of wear resistant ultrahigh molecular weight polyethylene (UHMWPE) for total joint replacement. Radiation crosslinking has been used to decrease wear through decreased plastic deformation; but crosslinking also reduces mechanical properties including fatigue resistance, a major factor limiting the longevity of joint implants. Reducing UHMWPE wear with minimal detriment to mechanical properties is an unaddressed need for articular bearing surface development. Here we report a novel approach to achieve this by limiting crosslinking to the articular surface. The antioxidant vitamin E reduces crosslinking efficiency in UHMWPE during irradiation with increasing concentration, thus we propose to spatially control the crosslink density distribution by controlling the vitamin E concentration profile. Surface crosslinking UHMWPE prepared using this approach had high wear resistance and decreased crosslinking in the bulk resulting in high fatigue crack propagation resistance. The interface region did not represent a weakness in the material due to the gradual change in the crosslink density. Such an implant has the potential of decreasing risk of fatigue fracture of total joint implants as well as expanding the use of UHMWPE to younger and more active patients.

Delamination and adhesive wear behavior of alpha-tocopherol-stabilized irradiated ultrahigh-molecular-weight polyethylene.

Wear and delamination of conventional ultrahigh-molecular-weight polyethylene (UHMWPE) components used in total knee arthroplasty can compromise long-term performance. Radiation cross-linking and melt-annealing reduced wear and increased delamination resistance of UHMWPE. An alternative material is the alpha-tocopherol-stabilized irradiated UHMWPE (alphaTPE), with improved mechanical and fatigue properties vs irradiated and melted UHMWPE. We studied the wear and delamination resistance of alphaTPE and conventional UHMWPE (direct compression molded GUR 1050 and Himont 1900) under reciprocating unidirectional motion. Wear resistance was improved, and no delamination was observed in alphaTPE. Accelerated aging did not alter the wear and delamination behavior of alphaTPE. The GUR 1050 UHMWPE showed delamination and pitting when subjected to unidirectional reciprocating motion after accelerated aging. Himont 1900 UHMWPE showed no delamination when subjected to unidirectional reciprocating motion after accelerated aging. alpha-Tocopherol-stabilized irradiated UHMWPE is advanced for use in total knee arthroplasty due to its high resistance to wear, delamination, and oxidation.

Fracture of a cross-linked polyethylene liner due to impingement.

We report a case of fracture at 2 years after implantation of a 50-kGy moderately cross-linked ultrahigh molecular weight polyethylene liner with an extended lip (Marathon, DePuy, Warsaw, IN). The extended lip section had fractured. The liner showed no oxidation. The articular surface was grossly deformed, likely due to wear, creep, and/or plastic deformation, and the liner showed no recovery of machining marks upon melting, indicating that some wear had occurred. Electron microscopy revealed fatigue striations on the fracture surface. The likely cause of failure was femoral neck impingement-induced wear and fatigue on the liner.

Diffusion of vitamin E in ultra-high molecular weight polyethylene.

Vitamin E-doped, radiation crosslinked ultra-high molecular weight polyethylene (UHMWPE) is developed as an alternate oxidation and wear resistant bearing surface in joint arthroplasty. We analyzed the diffusion behavior of vitamin E through UHMWPE and predicted penetration depth following doping with vitamin E and subsequent homogenization in inert gas used to penetrate implant components with vitamin E. Crosslinked UHMWPE (65- and 100-kGy irradiation) had higher activation energy and lower diffusion coefficients than uncrosslinked UHMWPE, but there were only slight differences in vitamin E profiles and penetration depth between the two doses. By using homogenization in inert gas below the melting point of the polymer following doping in pure vitamin E, the surface concentration of vitamin E was decreased and vitamin E stabilization was achieved throughout a desired thickness. We developed an analytical model based on Fickian theory that closely predicted vitamin E concentration as a function of depth following doping and homogenization.

The effect of alpha-tocopherol on the oxidation and free radical decay in irradiated UHMWPE.

We developed a radiation cross-linked ultra-high molecular weight polyethylene (UHMWPE) stabilized with alpha-tocopherol (Vitamin E) as a bearing material in total joint replacements. The stabilizing effect of alpha-tocopherol on free radical reactions in UHMWPE is not well understood. We investigated the effect of alpha-tocopherol on the oxidation and transformation of residual free radicals during real-time aging of alpha-tocopherol-doped, irradiated UHMWPE (alphaTPE) and irradiated UHMWPE (control). Samples were aged at 22 degrees C (room temperature) in air, at 40 degrees C in air and at 40 degrees C in water for 7 months. During the first month, alphaTPE showed some oxidation at the surface, which stayed constant thereafter. Control exhibited substantial oxidation in the subsurface region, which increased with time. The alkyl/allyl free radicals transformed to oxygen centered ones in both materials; this transformation occurred faster in alpha-TPE. In summary, the real-time oxidation behavior of alpha-TPE was consistent with that observed using accelerated aging methods. This new UHMWPE is oxidation resistant and is expected to maintain its properties in the long term.

Migration stability of alpha-tocopherol in irradiated UHMWPE.

The oxidation resistance of irradiated ultra-high molecular weight polyethylene (UHMWPE) components used in total joint arthroplasty can be improved by adding alpha-tocopherol (vitamin E) through diffusion. To ensure long-term oxidative stability, a minimum alpha-tocopherol concentration needs to be maintained throughout these components. Migration of alpha-tocopherol out of the components is one mechanism that could compromise long-term oxidative stability. We hypothesized that alpha-tocopherol could elute out during standard implant fabrication steps such as cleaning as well as during in vivo use. We doped 85 kGy irradiated UHMWPE with alpha-tocopherol at 120 degrees C and homogenized at 120 degrees C. We determined the extent of elution of alpha-tocopherol or its effect on oxidative stability following cleaning in isopropyl alcohol (IPA) and following 5 million cycles (MC) of simulated normal gait in bovine serum. There was no significant elution of alpha-tocopherol in repeated and prolonged cleaning in IPA as measured by average surface and bulk alpha-tocopherol concentrations. There was no change in the oxidative stability following 5 MC of hip simulator testing, indicating minimal elution during simulated normal gait.