Aims. Highly cross-linked polyethylene (HXLPE) greatly reduces wear in total hip arthroplasty, compared to conventional polyethylene (CPE). Cross-linking is commonly achieved by irradiation. This study aimed to compare the degree of cross-linking and in vitro wear rates across a cohort of retrieved and unused polyethylene cups/liners from various brands. Methods. Polyethylene acetabular cups/liners were collected at one centre from 1 April 2021 to 30 April 2022. The trans-vinylene index (TVI) and oxidation index (OI) were determined by Fourier-transform infrared spectrometry. Wear was measured using a pin-on-disk test. Results. A total of 47 specimens from ten brands were included. The TVI was independent of time in vivo. A linear correlation (R. 2. = 0.995) was observed between the old and current TVI standards, except for vitamin E-containing polyethylene. The absorbed irradiation dose calculated from the TVI corresponded to product specifications for all but two products. For one electron beam-irradiated HXLPE, a mean dose of 241% (SD 18%) of specifications was determined. For another, gamma-irradiated HXLPE, a mean 41% (SD 13%) of specifications was determined. Lower wear was observed for higher TVI. Conclusion. The TVI is a reliable measure of the absorbed irradiation dose and does not alter over time in vivo. The products of various brands differ by manufacturing details and consequently cross-linking characteristics. Absorption and penetration of electron radiation and gamma radiation differ, potentially leading to higher degrees of cross-linking for electron radiation. There is a non-linear, inverse correlation between TVI and in vitro wear. The wear resistance of the HXLPE with low TVI was reduced and more comparable to CPE. Cite this article: Bone Joint Res 2024;13(11):682–693

Introduction and Aims: Wear of ultra-high molecular weight polyethylene (UHMWPE) acetabular cups is a well-known cause of osteolysis and loosening of the components. Improvement of the wear resistance of UHMWPE could extend the clinical life of total hip arthroplasty (THA). Chemical cross-linking in acetylene with gamma radiation is a cheap and effective way of increasing wear resistance of UHMWPE. Method: This study is a report on 132 patients operated between 1977 and 1984, using the Pretoria monobloc stainless steel hip with 30mm metal head. Acetabular cups were machined from RAM extruded rectangular bars (RCH 1000). Final cups were gamma irradiated in stainless steel containers filled with acetylene gas. Three hundred microns surface cross-linking was achieved at 100kG. At that time, 1059 hip replacements were performed by the two first authors. The retrospective study consisted of measurement of the radiological wear. The criteria was to compare and measure the wear from early post-op radiograph and longest follow-up radiograph. Linear wear was measured according to the Livermore methods. Exclusion criteria included follow-up less than 10 years, sepsis, dislocation and other non wear-related causes of failure. The rarely retrieved cross-linked ace-tabular cups were analysed individually using spectrum electron microsope (SEM). Conclusion: The South African contribution to the method of cross-linking is important. This is a cheap and effective way to improve the quality of the polyethylene. Results of this long-term group of patients with cross-linked UHMWPE show a significant decrease in the wear rate, significantly increasing the longevity of the THR

Abstract. Objective. Clinical treatments to repair articular cartilage (AC) defects such as autologous cartilage implantation (mosaicplasty) often suffer from poor integration with host tissue, limiting their long-term efficacy. Thus to ensure the longevity of AC repair, understanding natural repair mechanisms that allow for successful integration between cartilaginous surfaces, as has been reported in juvenile tissue, may be key. Here, we evaluated cartilage integration over time in a pig explant model of natural tissue repair by assessing expression and localisation of major ECM proteins, enzymatic cross-linkers including the five isoforms of lysyl oxidase (LOX), small leucine-rich repeat proteoglycans (SLRP's), and proteases (e.g. ADAMTS4). Methods. AC was retrieved from the femoral condyles of 8-week-old pigs. Full thickness 6mmØ AC discs were prepared, defects were induced, and explants cultured for up to 28 days. After fixation, sections were stained using Safranin-O and antibodies against Collagen types I & II, LOX, and ADAMTS4. Gene expression analyses were performed using qPCR. We also cultured devitalized samples, either with or without enzymatic treatment to deplete proteoglycans, for 28 days and similarly assessed repair. Results. Safranin-O staining demonstrated successful integration of cartilage defects over a 28-day period. No significant regulation in the expression of Col1a1, Col2a1, LOX or SLPR genes was observed at any time point. Immunofluorescence staining revealed that only ADAMTS4 localized at the injury surface in integrated samples. Interestingly, we also observed successful spontaneous integration of proteoglycan-depleted devitalized tissue. Conclusion. Cartilage integration in our pig cartilage explant model did not appear to be mediated by upregulation of major cartilage ECM components, enzymatic cross-linkers, or SLRPs. However, spontaneous integration of devitalized, proteoglycan-depleted AC, and localised upregulation of ADAMTS4 at the injured surface in successfully integrated samples, suggest that ADAMTS4 may enhances normal repair in injured AC through local aggrecan depletion, therefore enabling spontaneous cross-linking of collagen fibrils. Declaration of Interest. (b) declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research reported:I declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research project

We carried out a prospective randomised study designed to compare the penetration rate of acetabular polyethylene inserts of identical design but different levels of cross-linking at a minimum of four years follow-up. A total of 102 patients (102 hips) were randomised to receive either highly cross-linked Durasul, or contemporary Sulene polyethylene inserts at total hip replacement. A single blinded observer used the Martell system to assess penetration of the femoral head. At a mean follow-up of 4.9 years (4.2 to 6.1) the mean femoral head penetration rate was 0.025 mm/year (. sd. 0.128) in the Durasul group compared with 0.106 mm/year (. sd. 0.109) in the Sulene group (Mann-Whitney test, p = 0.0027). The mean volumetric penetration rate was 29.24 mm. 3. /year (. sd. 44.08) in the Durasul group compared with 53.32 mm. 3. /year (. sd. 48.68) in the Sulene group. The yearly volumetric penetration rate was 55% lower in the Durasul group (Mann-Whitney test, p = 0.0058). Longer term results are needed to investigate whether less osteolysis will occur

Wear of ultra-high molecular weight polyethylene (UHMWP) acetabular cups is a well-known cause of osteolysis and loosening of the components. Improvement of the wear resistance of UHMWP could extend the clinical life of total hip arthroplasty (THA). Chemical cross-linking in acetylene with gamma radiation is a cheap and effective way of increasing wear resistance of UHMWP. This study is a report on 263 patients (123 males and 140 females) on whom Dr Weber performed THA between 1977 and 1984, using the Pretoria (Grobbelaar) monobloc stainless steel hip with 30-mm metal head. There were 96 patients (107 prostheses) available for follow-up at a mean of 18.3 years, with 89 surviving prosthesis in 79 patients (83.2%). We collected complete sets of radiographs of 54 patients (mean age 71.4 years) for a radiological survey in 1999. In 41 patients (76%) we found no wear. The mean age of these patients was 72 years. Wear was noted in the other 13 patients (24%), whose mean age was 75 years. The mean follow-up time was 16 years (8 to 23). The mean magnification in the radiological study was 18%. Mean wear for the total group was 1.29 mm and mean annual wear 0.17 mm. A similar analysis performed on a group of 64 of Dr Grobbelaar’s patients at 15.5 year mean follow-up shows remarkable similarity, with mean wear of 0.172 mm for a group of 64 patients and annual wear 0.11 mm. Dr Oonishi of Japan, who has conducted the only other long-term follow-up, found similarly promising results

The mechanical failure of ultra-high molecular weight polyethylene (UHMWPE) acetabular cups in vivo is due mainly to a combination of excessive plastic flow and fretting. Localised overheating of the bearing surface, due to insufficient lubrication, causes this. The purpose of this study was to determine the amount of creep in UHMWPE under various conditions. Test pieces were cut from a piece of raw material and tested according to ASTM D2990. In the first test, to determine the anisotropic behaviour of the material, test pieces of raw material were cut at various orientations. The material was then tested in the virgin state and the virgin state at different temperatures. It was also gamma sterilised under different conditions, namely 24 kGy in air, 25 kGy in a nitrogen atmosphere and 25 kGy in air, and heat treated at 80°C to get an annealing effect. Further tests were conducted to determine the effect of cross-linking on creep behaviour. These tests were administered at room temperature, at 50°C and at 60°C. The material showed extreme anisotropic behaviour. It was more sensitive to creep in the centre of the bar than on the outside (32%). Maximum creep, however, occurred at a 45°-angle. This is significant if we assume that maximum loading of an acetabular cup occurs at an angle of 70.7°. The difference in creep for the virgin material, measured at room temperature and at 60°C, was 87.3% or 0.716 mm. The variance in creep for the different methods of sterilisation was a maximum of 0.3 mm. Creep for the cross-linked material, however, was markedly less than for the virgin material. There was a decrease of 36% (0.58 mm) in creep at room temperature and almost 83% (0.84 mm) at 60°C. The test results show that the cross-linked material is much more stable. This may explain the good in-vivo service of these products

Hydrogels are hydrated 3-dimensional (3D) polymer networks that can be chemically or physically crosslinked. Interest in the use of hydrogels for tissue engineering applications has been growing in the past few decades due to their excellent biocompatibility and biodegradability. One of the major drawbacks of the use of hydrogels in such applications is their lack of structural strength. To address this, in this work, we have combined two hydrogel types, namely gelatin and alginate. In this work, a 1 ml volume of gelatin alginate hydrogel was molded in each well of a 24 well-plate and crosslinked with different concentrations of calcium chloride (CaCl₂) (20, 40, 60, 80, and 100 mM) to investigate the influence of concentration on hydrogel properties and cell viability. The hydrogel was characterized using Fourier transform infrared (FTIR) spectrometry, environmental scanning electron microscopy (ESEM), and an Alamar blue assay to assess the chemical structure, the surface morphology, and the epithelial cell viability of the hydrogel, respectively. The FTIR analysis shows that network formation improved with increasing concentration; decreased ion-polymer interactions have been noted for concentrations ≤ 60 mM. This appears to be in agreement with ESEM images that show an evolution from a smooth, featureless surface to the appearance of surface pore structure for concentrations ≥ 80 mM. Perhaps as ion concentration increases and network formation improves, the effect is evidenced as surface porosity; low concentrations result in swelling and a smooth surface. In terms of cell viability, viability has been found to increase with increasing concentration. The cell viability is 90 % at 100 mM CaCl₂, in contrast to 50 % for a concentration of 20 mM after 9 days of incubation. It is possible that the reduced viability can be attributed to the high proportion of uncrosslinked polymer chains at low concentrations. Overall, these results provide useful information about the role of crosslinking concentration on hydrogel properties, knowledge that may be applied to 3D bioprinting.

A method to extensively cross-link polyethylene for total hip application has been developed and tested in hip wear simulation. Extensively cross-linked polyethylene was prepared by exposing GUR 1050 polyethylene resin to 90 kg to 110 kg of e-beam radiation. For total hip application, the material was evaluated in an AMTI joint simulator in normal debris-free conditions and in a Shorewestern simulator for the adverse condition of added bone cement and aluminum oxide debris. The normal condition testing was conducted to 30 million cycles, while the adverse condition tests were conducted to 5 million cycles. Femoral head sizes from 22 mm to 46 mm were evaluated. The wear performance of extensively cross-linked material was compared to control material (GUR 1050 gamma sterilized in nitrogen). The results demonstrate a significant improvement in wear (greater than 80 percent reduction) of extensively cross-linked GUR 1050 acetabular components compared to the control acetabular components. The adverse condition wear of both materials was greater than the normal wear; however, when compared to the controls, the extensively cross-linked material had improved wear performance in both normal and adverse conditions. The wear of femoral heads larger than normal 32 mm sizes showed accelerated wear in the control material and desirable low wear in the extensively cross-linked condition. The polyethylene particles generated in the wear simulation were of similar size and shape between the extensively cross-linked and controlled polyethylene. As demonstrated in the laboratory simulation, this extensively cross-linked polyethylene has the potential to substantially reduce particular debris generation in total hip applications. A multicenter randomized controlled clinical study of extensively cross-linked and control acetabular components is ongoing.

Tendon is a bradytrophic and hypovascular tissue, hence, healing remains a major challenge. The molecular key events involved in successful repair have to be unravelled to develop novel strategies that reduce the risk of unfavourable outcomes such as non-healing, adhesion formation, and scarring. This review will consider the diverse pathophysiological features of tendon-derived cells that lead to failed healing, including misrouted differentiation (e.g. de- or transdifferentiation) and premature cell senescence, as well as the loss of functional progenitors. Many of these features can be attributed to disturbed cell-extracellular matrix (ECM) or unbalanced soluble mediators involving not only resident tendon cells, but also the cross-talk with immigrating immune cell populations. Unrestrained post-traumatic inflammation could hinder successful healing. Pro-angiogenic mediators trigger hypervascularization and lead to persistence of an immature repair tissue, which does not provide sufficient mechano-competence. Tendon repair tissue needs to achieve an ECM composition, structure, strength, and stiffness that resembles the undamaged highly hierarchically ordered tendon ECM. Adequate mechano-sensation and -transduction by tendon cells orchestrate ECM synthesis, stabilization by cross-linking, and remodelling as a prerequisite for the adaptation to the increased mechanical challenges during healing. Lastly, this review will discuss, from the cell biological point of view, possible optimization strategies for augmenting Achilles tendon (AT) healing outcomes, including adapted mechanostimulation and novel approaches by restraining neoangiogenesis, modifying stem cell niche parameters, tissue engineering, the modulation of the inflammatory cells, and the application of stimulatory factors. Cite this article: Bone Joint Res 2022;11(8):561–574

Introduction. Highly cross-linked ultrahigh molecular weight polyethylene (UHMWPE) is the most common bearing surface used in total joint arthroplasty due to its excellent wear resistance. While radiation cross-linking is currently used, cross-linking using a cross-linking agent such as a peroxide can also be effective with improved oxidative stability, which can be achived by an antioxidant such as vitamin E. The peroxide cross-linking behavior of UHMWPE in the presence of vitamin E was unknown. We investigated the cross-linking behavior and the clinically relevant mechanical and wear properties of peroxide cross-linked, vitamin E-blended UHMWPE. Materials and Methods. Medical grade UHMWPE (GUR1050) was blended with vitamin E and the peroxide (2,5-Dimethyl-2,5-di(t-butylperoxy)hexyne-3 or P130) before compression molding. Various vitamin E (0.1, 0.2, 0.3, 0.5, 0.6, 0.8 and 1.0 wt%) and peroxide concentrations (0.5, 1 and 1.5 wt%) were studied. The cross-link density was calculated as previously described (Oral 2010). The wear rate was determined using a custom-designed pin-on-disc wear tester against CoCr polished discs at 2 Hz and a rectangular path of 5 × 10 mm in undiluted bovine serum (Bragdon 2001). Tensile mechanical properties were determined using Type V dogbones according to ASTM D638. Oxidative stability was determined using oxidation induction testing (Braithwaite 2010). Double-notching and IZOD impact testing was performed according to ASTM D256. Samples prepared with vitamin E concentrations of 0.3 wt% and above and P130 concentrations of 0.5 and 1 wt% were also terminally gamma sterilized. Controls were 150-kGy irradiated vitamin E blends of UHMWPE. Results and Discussion. The cross-link density of peroxide cross-linked UHMWPEs were higher than the irradiated controls at a given vitamin E concentration (For example 250, 301 and 355 mol/dm3 for 0.5, 1 and 1.5 wt% peroxide cross-linked UHMWPE compared to 217 mol/dm3 for 150 kGy irradiated UHMWPE; Figure 1). The cross-link density dependence of wear was similar to radiation cross-linked UHMWPE, resulting in clinically relevant wear rates of 0.5 to 1.5 mg/MC. While the cross-link density of radiation cross-linked UHMWPE became saturated at vitamin E concentrations above 0.3 wt% (Oral 2008), this was not observed in peroxide cross-linked UHMWPE (Figure 2), suggesting more efficient cross-linking in the presence of the antioxidant. The impact strength was 30% higher for the peroxide cross-linked UHMWPEs at the comparable wear rate compared to irradiated controls (72 vs. 56 kJ/m2). The oxidation induction time of all peroxide cross-linked UHMWPEs (up to 57 min) was higher than that of the 0.1 wt% vitamin E-blended, 150-kGy irradiated UHMWPE (6 min). Gamma sterilization of peroxide cross-linked vitamin E blends decreased wear (0.5 wt% peroxide in Figure 3). Thus, peroxide concentration for cross-linking can be reduced if terminal sterilization is used. The mechanical properties and the oxidative stability of the material were not significantly affected by gamma sterilization. Significance. Peroxide cross-linking enabled good wear resistance for high vitamin E concentration blends of UHMWPE (>0.3 wt%), previously not possible by irradiation. Peroxide cross-linking of vitamin E-blended UHMWPE can provide a one-step, cost-effective method to manufacture wear resistant total joint implants with improved oxidative stability

Introduction. In vivo, UHMWPE bearing surfaces are subject to wear and oxidation that can lead to bearing fatigue or fracture. A prior study in our laboratory of early antioxidant (AO) polyethylene retrievals, compared to gamma-sterilized and highly cross-linked (HXL) retrievals, showed them to be more effective at preventing in vivo oxidation. The current analysis expands that early study, addressing the effect of:. manufacturing-variables on as-manufactured UHMWPE;. in vivo time on these initial properties;. identifying important factors in selecting UHMWPE for the hip or knee. Methods. After our prior report, our IRB-approved retrieval laboratory received an additional 96 consecutive AO-retrievals (19 hips, 77 knees: in vivo time 0–6.7 years) of three currently-marketed AO-polyethylenes. These retrievals represented two different antioxidants (Vitamin E and Covernox) and two different delivery methods: blending-prior-to and diffusing-after irradiation cross-linking. Consecutive HXL acetabular and tibial inserts, received at retrieval, with in vivo time of 0–6.7 years (260 remelted, 170 annealed) were used for comparison with AO-retrievals. All retrievals were analyzed for oxidation and trans-vinylene index (TVI) using a Thermo-Scientific iN10 FTIR microscope. Mechanical properties were evaluated for 35 tibial inserts by uniaxial tensile testing using an INSTRON load frame. Cross-link density (n=289) was measured using a previously published gravimetric gel swell technique. Oxidation was reported as maximum ketone oxidation index (KOI) measured for each bearing. TVI was reported as the average of all scans for each material. Cross-link density and mechanical properties were evaluated as a function of both TVI and oxidation. Results. Minimal increase in oxidation was seen in these AO-retrievals, out to almost 7 years in vivo. In contrast, HXL-retrievals showed increasing KOI with time in vivo (annealed-HXL = 0.127/year, remelted-HXL = 0.036/year, p<0.001). HXL oxidation rate was higher in knees (0.091/year) than in hips (0.048/year), p<0.001. Cross-link density (XLD) correlated positively with TVI for both HXL (Pearson's correlation=0.591, p<0.001) and AO (Pearson's correlation=0.598, p<0.001) retrievals. AO-materials had higher TVI for the same or similar XLD than did HXL polyethylene. XLD correlated negatively with KOI for HXL retrievals (Pearson's correlation=−0.447, p<0.001). Mechanical properties varied by material across all materials evaluated, with tensile toughness correlating negatively with increasing TVI (Pearson Correlation=−0.795, p<0.001). Discussion. Irradiation cross-linking has been used effectively to improve wear resistance. Residual free radicals from irradiation are the target of AO-polyethylene, to prevent loss of UHMWPE XLD, resulting from in vivo oxidation of free radicals as seen in HXL retrievals, and toughness, resulting from oxidation or initial remelting. Despite different manufacturing variables, AO-polyethylene retrievals in this cohort had minimal oxidation and no change in XLD or toughness due to oxidation. However, toughness did vary with irradiation dose as did cross-link density. To achieve the same level of cross-linking as HXL-polyethylene required a higher irradiation dose in blended AO-polyethylene. AO-polyethylenes evaluated in this study had toughness that decreased with irradiation dose, but avoided loss of toughness due to remelting. Because AO-polyethylenes did not oxidize, they did not show the decrease of cross-link density, and potential loss of wear resistance, seen in HXL-polyethylene. For any figures or tables, please contact authors directly

Aim. To assess the effect of different polyethylene modifications on Total Hip Replacement survival. Methods. We combined the NJR dataset with polyethylene manufacturing properties as supplied by the manufacturers. Cause specific and overall reasons for revisions were analysed using Kaplan-Meier and multi-variate Cox proportional hazard regression survival analyses. Revision for aseptic loosening was the primary endpoint. Modification variables included resin type, radiation source, multiple cross-linking treatments, cross-linking dose, terminal sterilisation method, terminal sterilisation radiation dose, stabilisation treatment, total radiation dose, and packaging. Results. A total of 292,920 primary THR cases were included with an associated 5,329 revisions. The variables found to significantly affect implant survival were the total radiation dose, liner face asymmetry, and stabilisation treatment. Total radiation dose was divided into four groups: G1 (no radiation); G2 (>0 Mrad and <5 Mrad); G3 (>5 Mrad and <10 Mrad), and G4 (>10 Mrad). The adjusted Cox Regression model with revision for aseptic loosening as the endpoint (G1 as reference) revealed a HR of 0.74 (0.64, 0.86) for G2, HR 0.36 (0.30, 0.43) for G3 and HR 0.38 (0.31, 0.47) for G4. In groups 3 and 4, stabilisation with vitamin E and heating above melting point performed best. Conclusion. Irradiation of polyethylene with 5MRad or more was associated with a marked reduction in the risk of revision for aseptic loosening. Irradiation with higher doses was not associated with a further reduction at 12 years of follow up

Summary. Low energy irradiation of vitamin E blended UHMWPE is feasible to fabricate total joint implants with high wear resistance and impact strength. Introduction. Irradiated ultra-high molecular weight polyethylene (UHMWPE), used in the fabrication of joint implants, has increased wear resistance. But, increased crosslinking decreases the mechanical strength of the polymer, thus limiting the crosslinking to the surface is desirable. Here, we used electron beam irradiation with low energy electrons to limit the penetration of the radiation exposure and achieve surface cross-linking. Methods. Medical grade 0.1wt% vitamin E blended UHMWPE (GUR1050) was consolidated and irradiated using an electron beam at 0.8 and 3 MeV to 150 kGy. Fourier Transform Infrared Spectroscopy (FTIR) was used from the surface along the depth at an average of 32 scans and a resolution of 4 cm. −1. A transvinylene index (TVI) was calculated by normalizing the absorbance at 965 cm. −1. (950–980cm. −1. ) against 1895 cm. −1. (1850 – 1985 cm. −1. ). TVI in irradiated UHMWPE is linearly correlated with the radiation received [3]. Vitamin E indices were calculated as the ratio of the area under 1265 cm. −1. (1245–1275 cm. −1. ) normalized by the same. Pin-on-disc (POD) wear testing was conducted on cylindrical pins (9 mm dia., 13 mm length, n=3) as previously described at 2 Hz [4] for 1.2 million cycles (MC). Wear rate was measured as the linear regression of gravimetric weight change vs. number of cycles from 0.5 to 1.2 MC. Double notched IZOD impact testing was performed (63.5 × 12.7 × 6.35mm) in accordance with ASTM F648. Cubes (1 cm) from 0.1wt% blended and 150 kGy irradiated pucks (0.8 MeV) were soaked in vitamin E at 110°C for 1 hour followed by homogenization at 130°C for 48 hours. Results. The penetration of the electron beam for cross-linking was limited at low beam energy and cross-linking of the surface 2 mm was achieved. The wear rate of samples irradiated at 0.8 and 3 MeV was 1.12±0.15, and 0.98±0.11, respectively (p»0.5). In addition, the wear rate of the surface (0.8 MeV) irradiated UHMWPE was 0.33±0.02 mg/MC 1 mm below the surface. The impact strength of UHMWPE irradiated at 0.8 MeV was 73 kJ/m. 2. and 54.2 kJ/m. 2. for that irradiated at 3 MeV (p=0.001). Doping with vitamin E and homogenization increased the surface vitamin E concentration from undetectable levels to 0.11±0.01. Discussion. The wear rate of this surface cross-linked UHMWPE was comparable to uniformly cross-linked UHMWPEs irradiated at higher electron beam energies. Even lower wear rate subsurface suggested the feasibility of machining 1 mm from the surface in implant fabrication. Limiting cross-linking to the surface resulted in higher impact strength compared to a uniformly cross-linked UHMWPE. Vitamin E was optionally replenished by additional doping after cross-linking; an advantage of this method may be increased oxidation resistance

Introduction:. Irradiated ultra-high molecular weight polyethylene (UHMWPE), used in the fabrication of joint implants, has increased wear resistance [1]. But, increased crosslinking decreases the mechanical strength of the polymer [2], thus limiting the crosslinking to the surface is desirable. Here, we usedelectron beam irradiation with low energy electrons to limit the penetration of the radiation exposure and achieve surface cross-linking. Methods:. Medical grade 0.1 wt% vitamin E blended UHMWPE (GUR1050) was consolidated and irradiated using an electron beam at 0.8 and 3 MeV to 150 kGy. Fourier Transform Infrared Spectroscopy (FTIR) was used from the surface along the depth at an average of 32 scans and a resolution of 4 cm. −1. A transvinylene index (TVI) was calculated by normalizing the absorbance at 965 cm. −1. (950–980 cm. −1. ) against 1895 cm. −1. (1850–1985 cm. −1. ). TVI in irradiated UHMWPE is linearly correlated with the radiation received [3]. Vitamin E indices were calculated as the ratio of the area under 1265 cm. −1. (1245–1275 cm. −1. ) normalized by the same. Pin-on-disc (POD) wear testing was conducted on cylindrical pins (9 mm dia., 13 mm length, n = 3) as previously described at 2 Hz [4] for 1.2 million cycles (MC). Wear rate was measured as the linear regression of gravimetric weight change vs. number of cycles from 0.5 to 1.2 MC. Double notched IZOD impact testing was performed (63.5 × 12.7 × 6.35 mm) in accordance with ASTM F648. Cubes (1 cm) from 0.1 wt% blended and 150 kGy irradiated pucks (0.8 MeV) were soaked in vitamin E at 110°C for 1 hour followed by homogenization at 130°C for 48 hours. Results:. The penetration of the electron beam for cross-linking was limited at low beam energy and cross-linking of the surface 2 mm was achieved (Fig 1). The wear rate of samples irradiated at 0.8 and 3 MeV was 1.12 ± 0.15, and 0.98 ± 0.11, respectively (p > 0.5). In addition, the wear rate of the surface (0.8 MeV) irradiated UHMWPE was 0.33 ± 0.02 mg/MC 1 mm below the surface. The impact strength of UHMWPE irradiated at 0.8 MeV was 73 kJ/m. 2. and 54.2 kJ/m. 2. for that irradiated at 3 MeV (p = 0.001). Doping with vitamin E and homogenization increased the surface vitamin E concentration from undetectable levels to 0.11 ± 0.01. Discussion:. The wear rate of this surface cross-linked UHMWPE was comparable to uniformly cross-linked UHMWPEs irradiated at higher electron beam energies. Even lower wear rate subsurface suggested the feasibility of machining 1 mm from the surface in implant fabrication. Limiting cross-linking to the surface resulted in higher impact strength compared to a uniformly cross-linked UHMWPE. Vitamin E was optionally replenished by additional doping after cross-linking; an advantage of this method may be increased oxidation resistance. Significance: Low energy irradiation of vitamin E blended UHMWPE is feasible to fabricate total joint implants with high wear resistance and impact strength

Introduction. Radiation cross-linked UHMWPE is preferred in total hip replacements due to its wear resistance [1]. In total knees, where stresses are higher, there is concern of fatigue damage [2]. Antioxidant stabilization of radiation cross-linked UHMWPE by blending vitamin E into the polymer powder was recently introduced [3]. Vitamin E greatly hinders radiation cross-linking in UHMWPE [4]. In contrast peroxide cross-linking of UHMWPE is less sensitive to vitamin E concentration [5]. In addition, exposing UHMWPE to around 300°C, increases its toughness by inducing controlled chain scission and enhanced intergranular diffusion of chains, simultaneously [6]. We present a chemically cross-linked UHMWPE with high vitamin E content and improved toughness by high temperature melting. Methods and Materials. Medical grade GUR1050 UHMWPE was blended with vitamin E and with 2,5-Di(tert-butylperoxy)-2,5-dimethyl-3-hexyne or P130 (0.5% Vitamin-E and 0.9% P130). The mixed powder was consolidated into pucks. The pucks were melted for 5 hours in nitrogen at 300, 310 and 320°C. One set of pucks melted at 310°C was accelerated aged at 70°C at 5 atm. oxygen for 2 weeks. Tensile mechanical properties were determined using ASTM D638. Izod impact toughness was determined using ASTM D256 and F648. Wear rate was determined using a bidirectional pin-on-disc (POD) tester with cylindrical pins of UHMWPE against polished CoCr discs in undiluted, preserved bovine serum. Results. The vinyl index increased as a function of temperature (Fig 1a). Cross-link density steadily decreased and impact strength increased with increasing vinyl index (Fig 1b). The ultimate tensile strength (UTS) was not affected by HTM (Table 2). Impact strength was significantly improved for all treatment temperatures (P<0.05) and wear was significantly increased only for the sample melted at 320°C (Table 2). Discussion. High temperature melting (HTM) was shown to increase toughness of UHMWPEs presumably due to controlled chain scissioning and increased intergranular diffusion of chains [6]. For radiation cross-linked UHMWPE, it was shown that an increase in elongation-at-break and impact strength could be obtained without sacrificing wear resistance up to an elongation of about 500% [7]. This vitamin E-blended, peroxide cross-linked, high temperature melted UHMWPE has very high oxidation resistance due to its high antioxidant content, high wear resistance due to cross-linking and much improved toughness, representing an optimum joint replacement surface. For figures/tables, please contact authors directly.

Introduction. The optimum UHMWPE orthopaedic implant bearing surface must balance wear, oxidation and fatigue resistance. Antioxidant polyethylene addresses free radicals, resulting from irradiation used in cross-linking, that could oxidize and potentially lead to fatigue damage under cycles of in vivo use. Assessing the effectiveness of antioxidant (AO) polyethylene compared to conventional gamma-sterilized or remelted highly cross-linked (HXL) polyethylene is necessary to set realistic expectations of the service lifetime of AO polyethylene in the knee. This study evaluates what short-term antioxidant UHMWPE retrievals can reveal about: (1) oxidation-resistance, and (2) fatigue-resistance of these new materials. Methods. An IRB-approved retrieval laboratory received 25 AO polyethylene tibial insert retrievals from three manufacturers with in vivo time of 0–3 years. These were compared with 20 conventional gamma-inert sterilized and 30 HXL (65-kGray, remelted) tibial inserts of the same in vivo duration range. The retrievals were. (1) analyzed for oxidation and trans-vinylene index (TVI) using an FTIR microscope, and (2) inserts of sufficient size and thickness were evaluated for mechanical properties by uniaxial tensile testing using an INSTRON load frame. Oxidation was reported as maximum oxidation measured in the scan from the articular surface to the backside of each bearing. TVI was reported as the average of all scans for each material. Average ultimate tensile strength (UTS), ultimate elongation (UE), and toughness were the reported mechanical properties for each material. Results. Maximum oxidation values differed significantly across material types (p=0.018, Figure 1). No antioxidant retrieval exhibited a subsurface oxidation peak, in contrast to conventional gamma-sterilized (55%) and highly cross-linked (37%) retrievals that exhibited subsurface oxidation peaks over the same in vivo time (Figure 2). Trans-vinylene index (TVI) correlated positively with nominal irradiation dose (p<0.001). Mechanical properties varied by material, with tensile toughness correlating negatively with increasing TVI (p<0.001, Figure 3). Discussion. AO polyethylene was developed to address the problem of free radicals in polyethylene resulting from irradiation used in cross-linking or sterilization. Each manufacturer used a different antioxidant or method of supplying the antioxidant. However, all of the antioxidant materials appeared to be effective at minimizing oxidation over the in vivo period of this study. The antioxidant materials prevented in vivo oxidation more effectively than both conventional gamma-sterilized and remelted HXL polyethylene, at least over the in vivo period represented. The toughness, or ability of the material to resist fatigue damage, decreased with increasing irradiation cross-linking dose (increasing TVI). The AO polyethylenes evaluated in this study had lower toughness than conventional gamma-sterilized polyethylene, but they avoided the loss of toughness due to remelting. Clinical relevance. Antioxidant polyethylene tibial retrievals showed superior oxidation resistance to conventional gamma-inert and remelted HXL inserts. Material toughness varied with the irradiation dose used to produce the material. Comparison of antioxidant retrieval tensile properties can be used as a guide for clinicians in choosing appropriate materials for the applications represented by their patients

The prevalent cause of implant failure after total joint replacement is aseptic loosening caused by wear debris. Improvement of the wear behaviour of the articulating bearing between the cup and femoral head is essential for increased survival rate of artificial hip joints. Cross-linking of the polyethylene (PE) material is one attempt to reduce wear particle release at the articulating surface. Various cross-linked polyethylenes (X-PE) are used in orthopaedics since several years. In total hip arthroplasty (THA) the use of larger femoral head sizes has specific reasons. Larger heads lead to a decreased risk of total hip dislocation and impingement as well as an improved range of motion in comparison to smaller head sizes like 28mm or less. However, the increasing diameter of femoral head can be associated with lower thickness of the PE liner and increased wear rate. Cross-linking of PE can improve the wear rate of the liner and hence supports the use of larger femoral heads. The aim of this experimental study was to evaluate the wear of standard vs. sequential X-PE (X3-PE) liner in combination with different ceramic femoral head sizes. Wear testing was performed for 5 million load cycles using standard UHMW-PE liners (N2Vac) and X3-PE liners (each Stryker GmbH & Co. KG, Duisburg, Germany) combined with 28mm ceramic ball heads and the Trident PSL acetabular cup (Stryker). Furthermore, X3-PE liners with an internal diameter of 36mm and 44mm and decreased wall thickness (5.9mm and 3.8mm) were combined with corresponding ceramic heads. An eight station hip wear simulator according to ISO 14242 (EndoLab GmbH, Rosenheim, Germany) was used to carry out the standard wear tests. The tests were realised in temperature-controlled chambers at 37°C containing calf serum (protein content 20g/l). The average gravimetrical wear rates of the standard UHMW-PE (N2Vac) liners combined with 28mm ceramic heads amounted to 12.6 ± 0.8mg/million cycles. Wear of X3-PE liners in combination with 28 mm ceramic heads was not detectable. The average gravimetrical wear rates of the X3-PE liners in combination with 36mm and 44mm ceramic heads amounted to 2.0 ± 0.5mg and 3.1 ± 0.3mg/million cycles, respectively. The purpose of this study was to evaluate the effect of femoral head size at THA on standard and sequential X-PE liner. The wear simulator tests showed that the wear rate of PE liners with small heads (28mm) decreased by cross-linking of the PE significantly. The amount of wear at X-PE increased slightly with larger head size (36mm and 44mm). However, by sequential cross-linking, the wear rate using thinner liners and larger femoral heads is reduced to a fractional amount of wear at conventional UHMW-PE. Hence, the above-mentioned advantages of larger femoral head diameters can be realised by improved wear behaviour of sequential X-PE

Improving the wear resistance of polyethylene is considered paramount to improving knee implant longevity. Consequently, a range of polymer fabrication techniques have evolved in the quest for a highly wear resistant material. The objective of this study was to explore the wear performance of polyethylene as fabricated in a variety of ways. The following materials were prepared, sterilised, artificially aged, and machined into wear specimens (n = 4 for each material): Compression molded GUR1050 with three levels of cross-linking (120 kGy, 65 kGy, and 0 kGy irradiation – control); ram extruded GUR4150 high modulus material; compression molded GUR4150 low modulus material; and HSS/PolySolidur/Hoechst reference polyethylene. Using a custom designed joint articular wear simulator, samples were loaded for 2 million cycles at a frequency of 0.5 Hz under loads of 2.1 kN. Tests were stopped every 250 000 cycles; and wear surfaces were examined microscopically for surface damage (pitting, cracking, delamination). After 2 million loading cycles the following specimens were pitted and delaminated: 2 GUR1050 control samples, 3 GUR4150 high modulus specimens, and all 4 reference polyethylene specimens. Burnishing, but no pitting, was seen in all GUR1050 elevated cross-linked polyethylene specimens, and in all GUR4150 low modulus specimens. The materials tested in this study represent a broad range of fabrication techniques. Differences in starting resin cannot fully account for the differences in wear behaviour seen between the groups; as damage was not limited to one resin group. The cross-linked specimens were melt-annealed, prior to cross-linking. It is possible that this processing step, and not the actual cross-linking, contributed to the improved wear performance of this group. However, of most interest is the comparable wear performance of GUR1050 cross-linked polyethylene and GUR4150 low modulus polyethylene suggesting that cross-linking polyethylene is not the only route towards obtaining a polyethylene with superior wear characteristics

Objectives. Advanced glycation end-products (AGEs) are a post-translational modification of collagen that form spontaneously in the skeletal matrix due to the presence of reducing sugars, such as glucose. The accumulation of AGEs leads to collagen cross-linking, which adversely affects bone quality and has been shown to play a major role in fracture risk. Thus, intervening in the formation and accumulation of AGEs may be a viable means of protecting bone quality. Methods. An in vitro model was used to examine the efficacy of two AGE-inhibitors, aminoguanidine (AG) and pyridoxamine (PM), on ageing human cortical bone. Mid-diaphyseal tibial cortical bone segments were obtained from female cadavers (n = 20, age range: 57 years to 97 years) and randomly subjected to one of four treatments: control; glucose only; glucose and AG; or glucose and PM. Following treatment, each specimen underwent mechanical testing under physiological conditions via reference point indentation, and AGEs were quantified by fluorescence. Results. Treatment with AG and PM showed a significant decrease in AGE content versus control groups, as well as a significant decrease in the change in indentation distance, a reliable parameter for analyzing bone strength, via two-way analysis of variance (ANOVA) (p < 0.05). Conclusions. The data suggest that AG and PM prevent AGE formation and subsequent biomechanical degradation in vitro. Modulation of AGEs may help to identify novel therapeutic targets to mitigate bone quality deterioration, especially deterioration due to ageing and in AGE-susceptible populations (e.g. diabetics). Cite this article: O. Abar, S. Dharmar, S. Y. Tang. The effect of aminoguanidine (AG) and pyridoxamine (PM) on ageing human cortical bone. Bone Joint Res 2018;7:105–110. DOI: 10.1302/2046-3758.71.BJR-2017-0135.R1

Abstract. Objectives. Ultra-High Molecular Weight Polyethylene (UHMWPE) can be made radiopaque through the diffusion of an oil-based contrast agent (Lipiodol Ultra-fluid). A similar process is used for Vitamin E incorporated polyethylene, which has a well-established clinical history. This study aimed to quantify the leaching of Lipiodol and compare to vitamin E polyethylene. Method. GUR 1050 polyethylene (4 mm thickness) was cut into squares, 10 mm. 2. Samples (n=5) were immersed in 25 ml Lipiodol (Guerbet, France), or 15 ml Vitamin E (L-atocopherol, Sigma-Aldrich, UK). To facilitate diffusion, samples were held at 105°C for 18 hours. After treatment, all samples were immersed in DMEM (Sigma-Aldrich, UK) with Penicillin Streptomycin (Sigma-Aldrich, Kent, UK) at 4%v/v and held at 37°C in an incubator. Untreated polyethylene samples were included as controls. Leaching was quantified gravimetrically at weeks 2, 4 and 8. The radiopacity of the Lipiodol-diffused samples was investigated from µCT images (162kV, resolution 0.2 mm, X Tec, XT H 225 ST, Nikon Metrology, UK). Results. The leaching of Lipiodol and Vitamin E followed the same trend and reached a steady state after week 2. At this point there was a 20% decrease in the Hounsfield Unit and droplets of radiopaque oil were visible in the DMEM solution; these were not evident in subsequent scans. Over 8 weeks of 20% Lipiodol leached out of the polyethylene, which was greater than of 10% Vitamin E. Conclusion. After 8 weeks the radiopaque polyethylene was still identifiable in CT scan images, even though 20% of leaching occurred. The leaching of Lipiodol may be mitigated through cross-linking, which has been shown to reduce leaching of Vitamin E; this will be investigated as future work. Declaration of Interest. (b) declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research reported:I declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research project