Polyethylene wear-debris induced inflammatory osteolysis is known as the main cause of aseptic loosening and long term revision total hip arthroplasty. Although recent reports suggest that antioxidant impregnated ultra-high molecular weight polyethylene (UHMWPE) wear-debris have reduce the osteolytic potential in vivo when compared to virgin UHMWPE, little is known about if and/or how PE rate of oxidation affects osteolysis in vivo. We hypothesized that oxidized UHMWPE particles would cause more inflammatory osteolysis in a murine calvarial bone model when compared to virgin UHMWPE. Male C57BL/6 eight weeks old received equal amount of particulate debris overlaying the calvarium of (n=12/group): sham treatment (no particles), 2mg (6,75×107 particles/mg) of endotoxin-free UHMWPE particles (PE) or of endotoxin-free highly oxidized-UHMWPE (OX) particles. In vivo osteolysis was assessed using high resolution micro-CT and inflammation with L-012 probe dependent luminescence. At day 10, calvarial bone was examined using high resolution micro-CT, histomorphometric, immunohistochemistry analyses and qRT-PCR to assess OPG, RANK, RANK-L, IL-10, IL-4, IL-1b and TRAP genes expression using the protocol defined by individual TaqManTM Gene Expression Assays Protocol (Applied Biosystems). In vivo inflammation was significantly higher in the OX (1.60E+06 ± 8.28E+05 photons/s/cm2) versus PE (8.48E+05 ± 3.67E+05) group (p=0.01). Although there was a statistically significant difference between sham (−0.27% ± 2.55%) and implanted (PE: −9.7% ± 1.97%, and OX: − 8.38% ± 1.98%) groups with regards to bone resorption (p=0.02), this difference was not significant between OX and PE (p = 0.14). There was no significant difference between groups regarding PCR analyses for OPG, RANK, RANK-L, IL-10, IL-4, IL-1b and TRAP (p = 0.6, 0.7, 0.1, 0.6, 0.3, 0.4, 0.7 respectively). Bone volume density was significantly decreased in PE (13.3%±1.2%) and OX (12.2%±1.2%) groups when compared to sham (15%±0.9%) (p < 0 .05). Histomorphometric analyses showed a significantly decreased Bone Thickness/Tissue Thickness ratio in the implanted group (0.41±0.01 mm and 0.43±0.01 mm) compared to sham group (0.69± 0.01) (p < 0 .001). However, there were no significant difference between OX and PE (p = 0.2). Our findings suggest that oxidized UHMWPE particles display increased inflammatory potential. Results were not significant regarding in vivo or ex vivo osteolysis. As antioxidant-diffused UHMWPE induce less inflammation activity in vivo, the mechanism by which they cause reduced osteolysis requires further investigation

Introduction. Ultra high molecular weight polyethylene (UHMWPE) has been used successfully as a bearing material in hip, knee, and shoulder joint replacements. However, there are problems to cause a failure in UHMWPE component, which are wear behavior and creep deformation. Continuous bearing motion and dynamic load have occurred to UHMWPE wear debris caused osteolysis in periprosthetic tissue and to plastic deformation of joint component, and subsequent aseptic loosening of components. Therefore, many studies have being carried out in order to reduce wear debris and to improve mechanical strength from UHMWPE, and there is tremendous improvement of mechanical property in UHMWPE from gamma irradiated conventional UHMWPE (GIPE), highly crosslinked PE (XLPE), and XLPE with vitamin E1, 2. Friction has a significant one of the factors effect on the wear and creep deformation. In this study, the short-term frictional behaviors of three typical types of GIPE, remelted XLPE (R-XLPE), and s annealed XLPE (A-XLPE), and XLPE with Vitamin E against Co-Cr alloy were compared under three levels of contact pressures which occured in hip, knee, and shoulder joints. Methods. Friction tests were conducted with UHMWPE against Co-Cr alloy by using pin-on-disk type triboteter. For test, tribotester performed in a repeat pass rotational slidintg motion with a velocity of 60rpm. Applied contact pressure selected three kinds of levels, 5, 10, and 20MPa which were within the range of maximum contact pressures for total hip, knee, and shoulder joint replacements. To analyze the frictional effect of UHMWPE type, it conducted t-test and p-values less than 0.05 were used to determine the statistically significant difference. Results. In this study, it was observed that coefficients of friction (COF) were affected by various conditions, kinds of materials and applied load. We can reveal the frictional behavior of UHMWPE in various contact pressures. The average of the COF measured that GIPE was 0.029∼0.0423, R-XLPE was 0.018∼0.031, A-XLPE was 0.023∼0.038, and XLPE with Vitamin E was 0.013∼0.027 under 5, 10, and 20MPa. Discussion. COF of R-XLPE, A-XLPE, and XPLE with Vitamin E were lower than GIPE for all levels of contact pressures. This study showed the trend that COF decreased as contact pressure increased. Also, XPLE with Vitamin E has lowest frictional values among UHMWPEs. In the viewpoint of applied load, it was decreased as a contact pressure increased for COF of GIPE, RXLPE, and AXLPE against Co-Cr alloy. COF of GIPE, XLPEs, and XLPE with Vitamin E against Co-Cr alloy were as low as using bio materials compared with the COF of cartilage to cartilage, which was about 0.024. Conclusions. In conclusion, average COF of XLPE with Vitamin E was significantly lower than those of R-XLPE and A-XLPE. XLPEs showed much lower COF than GIPE

Summary. Prosthetic UHMWPE added with vitamin E and crosslinked UHMWPE are able to decrease significantly the adhesion of various bacterial and fungal strains limiting biomaterial associated infection and consequent implant failure. Introduction. Polyethylene abrasive and oxidative wear induces overtime in vivo a foreign-body response and consequently osteolysis, pain and need of implant revision. To solve these problems the orthopaedic research has been addressed to develop new biomaterials such as a crosslinked polyethylene with a higher molecular mass than standard Ultra High Molecular Weight Polyethylene (UHMWPE), and consequently a higher abrasive wear resistance and an antioxidant (vitamin E)-added UHMWPE to avoid oxidative wear. Nevertheless a feared complication of implant surgery is bacterial or fungal infection, initiated by microbial adhesion and biofilm formation, and related to the biomaterial surface characteristics. Staphylococci are the most common microorganisms causing biomaterial associated infection (BAI), followed by streptococci, Gram-negative bacilli and yeasts. With the aim to prevent BAI, the purpose of this study was to evaluate the adhesion of various microbial strains on different prosthetic materials with specific surface chemical characteristics, used in orthopaedic surgery. Methods. We compared the effects of vitamin E-added UHMWPE and crosslinked UHMWPE with that of standard GUR 1020 UHMWPE, upon the adhesion of ATCC biofilm-producing strains of Staphylococcus epidermidis, S. aureus, Escherichia coli and Candida albicans. After different incubation times the samples were sonicated to release the attached microorganisms and spread onto agar to quantify colony forming units (UFC)/ml. The biomaterials were physico-chemically characterised by means of scanning electron microscopy (SEM), water contact angle (CA) measurements and attenuated total reflectance (ATR)-fourier transform infrared (FTIR) spectroscopy, before and after adhesion assays. The experiments were assayed in triplicate and repeated a minimum of three times. A statistical analysis on results was conducted. Results. No significant difference of the surface roughness, CA and ATR-FTIR spectroscopy was found among the different biomaterials. After 3 and 7 h of incubation microbial adhesion rates were similar with no statistically relevant differences among the samples assayed. On the contrary, after 24 and 48 h of incubation a significantly (p<0.05 and p<0.01) different adhesion trend was achieved on the three biomaterials, highlighting a microbial adhesion significantly lower on vitamin E-added UHMWPE and crosslinked UHMWPE compared with that on standard UHMWPE. Discussion/Conclusion. Standard UHMWPE, vitamin E-added UHMWPE and crosslinked UHMWPE were chosen because of their diffusion in the clinical use. Previously we showed that vitamin E addition to the UHMWPE reduces the adhesive ability of various staphylococcal strains, compared with standard UHMWPE, and we correlated this results with its antioxidant properties. The results of this study indicate a quite similar significant reduction of bacterial and fungal adhesion on either vitamin E-added UHMWPE and crosslinked UHMWPE, if compared to standard UHMWPE at 48h. Further analysis on the chemical- physical characteristics of the UHMWPE surfaces and on their morphology are needed to explain the different adhesions

Introduction. UHMWPE particle-induced osteolysis is one of the major causes of arthroplasty revisions. Recent in vitro findings have suggested that UHMWPE wear particles containing vitamin-E (VE) may have reduced functional biologic activity and decreased potential to cause osteolysis (Bladed C. L. et al, JBMR B 2012 and 2013). This is of significant importance since VE-stabilized cross-linked UHMWPEs were recently introduced for clinical use, and there is no in vivo data determining the effects of wear debris. In this study we hypothesized that particles from VE-stabilized, radiation cross-linked UHMWPE (VE-UHMWPE) would cause reduced levels of osteolysis in a murine calvarial bone model when compared to virgin gamma irradiated cross-linked UHMWPE. Methodology. Study groups were the following: 1). Radiation cross-linked VE-UHMWPE (0.8% by weight) diffused after 100 kGy; 2). Radiation cross-linked virgin UHMWPE (virgin UHMWPE); 3). Sham controls. Particle generation and implantation: UHMWPE was sent to Bioengineering Solutions (Oak Park, IL) for particle generation. After IACUC approval, C57BL/6 mice (n=12 for each group) received equal amount of particulate debris (3mg) overlying the calvarium and were euthanized after 10 days. Micro-CT scans: High resolution micro-CT scans were performed using a set voltage of 70 kV and current of 70 µA. Topographical Grading Scale: Each calvarial bone was blindly scored using the following scale: 0=No osteolysis, defined as intact bone; 1=Minimal osteolysis, affecting 1/3 or less of the bone area; 2=Moderate osteolysis, affecting at least 2/3 of the bone area; 3=Severe osteolysis, defined as completely osteolytic bone. Histology: H&E and TRAP staining was done on tissue to confirm micro-CT findings and quantify osteoclasts. Statistical Analysis: Inter-rater analysis was done using Cohen's kappa analysis. An inter-rater coefficient >0.65 was considered as high inter-rater agreement. Comparison between groups was made using one-way ANOVA with post hoc Bonferroni correction for multiple comparisons. Correlations are reported as Spearman's rho. P-value<0.05 was considered statistically significant. Results. More than 83% of the VE-UHMWPE and more than 85% of the virgin UHMWPE particles measured less than 1 µm in mean particle size. There was a statistically significant greater level of osteolysis visualized on the topographical grading scale in calvaria implanted with virgin UHMWPE wear particles. Micro-CT findings were confirmed histologically (Fig. 1). A greater amount of inflammatory tissue overlaying the calvaria was observed in the virgin UHMWPE group when compared to both shams and VE-UHMWPE groups. Post hoc analysis revealed significant difference between VE-UHMWPE and virgin UHMWPE for the topographical osteolysis grading score (p=0.002) but no difference in osteoclast counts (p=0.293). Discussion and Conclusion. This is the first in vivo study reporting the effects of clinically-relevant UHMWPE particles generated from a VE-UHMWPE implant that is in current clinical use. These results suggest that VE-UHMWPE particles have reduced osteolysis potential in vivo when compared to virgin, highly cross-linked UHMWPE in a murine calvarial bone model. Arthroplasty procedures using VE-UHMWPE might be less susceptible to peri-prosthetic loosening caused by wear debris

Summary Statement. Vitamin E-UHMWPE particles have a reduced osteolysis potential in vivo when compared to virgin, highly cross-linked UHMWPE in a murine calvarial bone model. Introduction. Ultra high-molecular weight polyethylene (UHMWPE) particle-induced osteolysis is one of the major causes of arthroplasty revisions. The lack of particle clearance from the joint inevitably leads to the upregulation of the inflammatory cascade, resulting in bone resorption and implant loosening. Recent in vitro findings (Bladed CL et al. ORS 2011 and J Biomed Mater Res B Appl Biomater, 2012) have suggested that UHMWPE wear particles containing vitamin-E (VE) may have reduced functional biologic activity and decreased potential to cause osteolysis. This is of significant importance since VE-stabilised cross-linked UHMWPEs were recently introduced for clinical use, and there is no in vivo data determining the effects of wear debris from this new generation of implants. In this study we hypothesised that particles from VE-stabilised, radiation cross-linked UHMWPE (VE-UHMWPE) would cause reduced levels of osteolysis in a murine calvarial bone model when compared to virgin gamma irradiated cross-linked UHMWPE. Methods. Study groups were the following: 1) Radiation cross-linked VE-UHMWPE, approximately 0.8% by weight, diffused after 100 kGy; 2). Radiation cross-linked virgin UHMWPE (virgin UHMWPE); 3). Shams. Particle generation and implantation: UHMWPE was sent to Bioengineering Solutions (Oak Park, IL) for particle generation. After IACUC approval, C57BL/6 mice (n=12 for each group) received equal amount of particulate debris (3mg) overlying the calvarium and were euthanised after 10 days. Micro-CT scans: High resolution micro-CT scans were performed using an X-Tek HMX ST 225 with a set voltage of 70 kV and current of 70 µA. Topographical Grading Scale: Each calvarial bone (interparietal, right and left parietal, right and left frontal) was blindly scored using the following scale: 0=No osteolysis, defined as intact bone; 1=Minimal osteolysis, affecting 1/3 or less of the bone area; 2=Moderate osteolysis, affecting at least 2/3 of the bone area; 3=Severe osteolysis, defined as completely osteolytic bone. Histological Analysis: H&E and TRAP staining was performed on tissue to confirm the micro-CT findings and to quantify osteoclasts. Statistical Analysis: Inter-rater analysis was performed using Cohen's kappa analysis. An inter-rater coefficient >0.65 was considered as high inter-rater agreement. Comparison between groups was made using one-way ANOVA with post hoc Bonferroni correction for multiple comparisons. Correlations are reported as Spearman's rho. A p-value<0.05 was considered statistically significant. Results. More than 83% of the VE-UHMWPE and more than 85% of the virgin UHMWPE particles measured less than 1 µm in mean particle size. The mean particle size for VE-UHMWPE was 1.12 µm (range 0.28 to 79.08 µm), while virgin UHMWPE particles measured 1.22 µm (range 0.28 to 82.04 µm). There was a statistically significant greater level of osteolysis visualized on the topographical grading scale in calvaria implanted with virgin UHMWPE wear particles. The micro-CT findings were confirmed histologically. A greater amount of inflammatory tissue overlaying the calvaria was observed in the virgin UHMWPE group when compared to both shams and VE-UHMWPE groups. Post hoc analysis revealed significant difference between VE-UHMWPE and virgin UHMWPE for the topographical osteolysis grading score (p = 0.002) but no difference in osteoclast count (p = 0.293). Discussion/Conclusion. This is the first in vivo study reporting the effects of clinically-relevant UHMWPE particles generated from a VE-UHMWPE implant that is in current clinical use. These results suggest that VE-UHMWPE particles have reduced osteolysis potential in vivo when compared to virgin, highly cross-linked UHMWPE in a murine calvarial bone model. Arthroplasty procedures using VE-UHMWPE might be less susceptible to peri-prosthetic loosening caused by wear debris

Introduction. In vitro findings (Bladed CL et al. ORS 2011 and J Biomed Mater Res B Appl Biomater, 2012) have suggested that UHMWPE wear particles containing vitamin-E (VE) may have reduced functional biologic activity and decreased osteolytic potential. Currently, there is no in vivo data determining the effects of wear debris from this new generation of implants. In this study we hypothesized that particles from VE-stabilized, radiation cross-linked UHMWPE (VE-UHMWPE) would cause reduced levels of osteolysis in a murine calvarial bone model when compared to virgin gamma irradiated cross-linked UHMWPE. Methods. Study groups: 1). Radiation cross-linked VE-UHMWPE, 0.8% by weight, diffused after 100 kGy; 2). Radiation cross-linked virgin UHMWPE (virgin UHMWPE); 3). Shams. Particle generation and implantation: UHMWPE was sent to Bioengineering Solutions for particle generation. After IACUC approval, C57BL/6 mice (n = 12 for each group) received 3 mg of particulate debris overlying the calvarium and euthanized after 10 days. Micro-CT scans: Performed using an X-Tek-HMX-ST-225 with 70 kV voltage and 70 μA current. Topographical Grading Scale: Each calvarial bone was blindly scored with the following scale: 0 = No osteolysis, defined as intact bone; 1 = Minimal osteolysis, affecting 1/3 or less of the bone area; 2 = Moderate osteolysis, affecting at least 2/3 of the bone area; 3 = Severe osteolysis, defined as completely osteolytic bone. Histology H&E and TRAP staining was performed. Statistical Analysis: Inter-rater analysis was performed using Cohen's kappa analysis. Inter-rater coefficient >0.65 was considered as high inter-rater agreement. Comparison between groups was made using one-way ANOVA with post hoc Bonferroni correction for multiple comparisons. Correlations are reported as Spearman's rho. A p-value<0.05 was considered statistically significant. Results. More than 83% of the VE-UHMWPE and more than 85% of the virgin UHMWPE particles measured less than 1 μm in mean particle size. There was a statistically significant greater level of osteolysis visualized on the topographical grading scale in calvaria implanted with virgin UHMWPE wear particles. The micro-CT findings were confirmed histologically (Fig. 1). A greater amount of inflammatory tissue overlaying the calvaria was observed in the virgin UHMWPE group when compared to both shams and VE-UHMWPE groups. Post hoc analysis revealed significant difference between VE-UHMWPE and virgin UHMWPE for the topographical osteolysis grading score (p = 0.002) but no difference in osteoclast count (p = 0.293). Discussion/Conclusion. This is the first in vivo study reporting the effects of clinically-relevant UHMWPE particles generated from a VE-UHMWPE implant that is in current clinical use. These results suggest that VE-UHMWPE particles have reduced osteolysis potential in vivo when compared to virgin, highly cross-linked UHMWPE in a murine calvarial bone model

Introduction. Periprosthetic joint infection (PJI) and particle-induced osteolysis are closely related to peri-implant local immunity and macrophage function. We previously demonstrated that titanium particles attenuate the immune response of macrophages caused by chronic inflammation [1]. In a separate study, we have determined that UHMWPE wear particles containing vitamin E (VE) induce less osteolysis compared to HXL UHMWPE wear particles in a murine calvarium model [2]. For this study we hypothesized that macrophages exposed to HXL UHMWPE particles containing VE would better maintain their ability to respond to S. aureus compared to HXL UHMWPE without VE. Methods. A gamma-sterilized, HXL UHMWPE tibial bearing containing VE (E1, Biomet, “VE-PE”) and 100kGy irradiated and melted UHMWPE (“CISM 100”) were cryomilled to particles by Bioengineering Solutions (Oak Park, IL). In the first in vitro study, RAW 264.7 mouse macrophages were exposed (inverted co-culture) to either VE-PE particles or CISM100 particles and lipopolysaccharide (LPS) for 1–7 days. Macrophage viability was measured using a cell counting kit (CCK-8). Control group with no particles and a LPS group were also included. Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining was performed to determine macrophage apoptosis rate in response to particle exposure over time. In the second study, macrophages were exposed to VE-PE or CISM100 particles for 48h, then exposed to LPS for 30 min. Subsequently, reactive oxygen species (ROS) generation and extracellular regulated protein kinase (ERK) phosphorylation were measured. In a third study, after exposure to particles for 48h, fatigued macrophages were co-cultured with bioluminescent S. aureus strain Xen29 for 3h and 6h. Bioluminescence signal was determined to measure the total amount of bacteria. Bacterial live/dead staining and optical density at 600 nm (OD 600) were also performed to determine S. aureus viability. Statistical analysis was performed using one-way or two-way ANOVA with a post hoc examination. *indicates p<0.05. Results. CISM100 particles significantly decreased macrophage viability at day 5 and day 7 (p<0.05, Fig. 1A), while the viability of macrophages exposed to VE-PE particles was similar to controls (macrophages not exposed to particles). After 48h, macrophages exposed to VE-PE particles showed a lower TUNEL-positive rate (less apoptosis) compared to CISM100 particles (Fig. 1B, C). 48h-exposure to VE-PE particles increased ROS generation and ERK phosphorylation in 30 min-LPS-activated macrophages when compared to CISM100 particles (Fig. 2). This immune response caused by VE-PE particles resembles that of macrophages without particles. Furthermore, 48h exposure to E1 particles showed less S. aureus at 6h (Fig. 3). Conclusions. These results suggest that VE-PE particles cause reduced macrophage apoptosis and protect the macrophages' immune response. VE-PE particles also preserved the innate immunity of macrophages, unlike CISM100, as evidenced by the S. aureus co-culture study. Thus, patients with vitamin-E containing implants may be less likely to develop PJI

Majority of ultra-high molecular weight polyethylene (UHMWPE) medical devices used in total joint arthroplasty are crosslinked using gamma radiation to improve wear resistance. Alternative methods of crosslinking are urgently needed to replace gamma radiation due to rapid decline in its supply. Peroxide crosslinking is a candidate method with widespread industrial applications. Oxidative stability and biocompatibility, which are critical requirements for medical device applications, can be achieved using vitamin-E as an additive and by removing peroxide by-products through high temperature melting, respectively. We investigated compression molded UHMWPE/vitamin-E/di-cumyl peroxide blends followed by high-temperature melting in inert gas as a material candidate for tibial knee inserts. Wear resistance increased and mechanical properties remained largely unchanged. Oxidation induction time was higher than most of the other clinically available formulations. The material passed the local-end point biocompatibility tests per ISO 10993. Compounds found in exhaustive extraction were of no concern with margin-of-safety values well above the accepted level, indicating a desirable toxicological risk profile. Peroxide crosslinked, vitamin-E stabilized, and high temperature melted UHMWPE has recently been cleared for clinical use in tibial knee inserts. With all the salient characteristics needed in a material that can provide superior long-term performance in total joint patients, peroxide crosslinking can replace gamma radiation crosslinking of UHMWPE for use in all total joint replacement implant including acetabular liners

Introduction. According to American Joint Replacement Registry, particle mediated osteolysis represents 13 % of the knee revision surgeries performed in the United States. The comprehension of mechanical and wear properties of materials envisioned for TJR is a key step in product development. Furthermore, the maintenance of UHMWPE mechanical properties after material modification is an important aspect of material success. Initial studies conducted by our research group demonstrated that the incorporation of ibuprofen in UHMWPE had a minor impact on UHMWPE physicochemical and mechanical properties. Drug release was also evaluated and resulted in an interesting profile as a material to be used as an anti-inflammatory system. Therefore, the present study investigated the effect of drug release on the mechanical and biological properties of ibuprofen-loaded UHMWPE. Experimental. UHMWPE resin GUR 1020 from Ticona was for sample preparation. Samples with drug concentrations of 3% and 5% wt were consolidated as well as samples without anti-inflammatory addition through compression molding at 150 °C and 5 MPa for 15 minutes. Mechanical properties were evaluated via the tensile strength experiment (ASTM D638) and dynamic mechanic tests. Wear resistance was measured using the pin on disc (POD) apparatus. Finally, cytotoxicity analysis was conducted based on ISO 10993–5. Results. Dynamic-mechanic analysis demonstrated no difference in flexion modulus and stress for all materials (Table 1). No difference was also verified during cyclical loading experiments (Table 1), which indicates that the drug concentration added to material composition did not affect these properties. POD experiments were proposed to evaluate wear resistance of ibuprofen-loaded UHMWPE samples considering the combination of materials similar to those employed in TJR. Results from POD tests are presented in Table 1. Volumetric wear was close to zero for all samples after 200 thousand cycles. Comprehension of the effect of drug release on mechanical properties is essential to estimate how the material will behave after implantation. Therefore, mechanical properties were assessed after 30 days of ibuprofen release and the results were compared with those obtained in samples as prepared (Table 2). Initial results demonstrated a decrease in elastic modulus in samples prepared with ibuprofen. However, no difference was verified between UHMWPE, UHMWPE 3% IBU and UHMWPE 5% IBU after ibuprofen release. Finally, cell viability of UHMWPE 3% IBU and UHMWPE 5% was found to be superior to 100% (Figure 1). Therefore, both materials can be considered nontoxic. Conclusions. Ibuprofen-loaded UHMWPE did not demonstrate a significant influence on the mechanical and biological behavior of UHMWPE. Dynamic-mechanical tests demonstrated constancy for all samples under analysis. Wear testing resulted in gravimetric wear close to zero, for all tested materials. Mechanical properties conducted after 30 days of ibuprofen release also had a positive outcome. Although presenting a difference in modulus prior and after release tests, modulus and tensile yield stress remained inside acceptable range indicated to UHMWPE used in orthopedic implants. Furthermore, after drug elution UHMWPE 3% IBU and UHMWPE 5% IBU recovered original UHMWPE properties. Cytotoxicity assessment was performed and both ibuprofen-based formulations were considered nontoxic according to ISO 10993–5. For any figures or tables, please contact the authors directly

Objectives. Unicompartmental knee arthroplasty (UKA) is an alternative to total knee arthroplasty with isolated medial or lateral compartment osteoarthritis. However, polyethylene wear can significantly reduce the lifespan of UKA. Different bearing designs and materials for UKA have been developed to change the rate of polyethylene wear. Therefore, the objective of this study is to investigate the effect of insert conformity and material on the predicted wear in mobile-bearing UKA using a previously developed computational wear method. Methods. Two different designs were tested with the same femoral component under identical kinematic input: anatomy mimetic design (AMD) and conforming design inserts with different conformity levels. The insert materials were standard or crosslinked ultra-high-molecular-weight polyethylene (UHMWPE). We evaluated the contact pressure, contact area, wear rate, wear depth, and volumetric wear under gait cycle loading conditions. Results. Conforming design inserts had the lower contact pressure and larger contact area. However, they also had the higher wear rate and volumetric wear. The improved wear performance was found with AMD inserts. In addition, the computationally predicted volumetric wear of crosslinked UHMWPE inserts was less than half that of standard UHMWPE inserts. Conclusion. Our results showed that increasing conformity may not be the sole predictor of wear performance; highly crosslinked mobile-bearing polyethylene inserts can also provide improvement in wear performance. These results provide improvements in design and materials to reduce wear in mobile-bearing UKA. Cite this article: Bone Joint Res 2019;8:563–569

Introduction. Infection remains as one of the major challenges of total joint surgery. One-stage irrigation, debridement and reimplantation, or two-stage revision surgery with a temporary implantation of antibiotic eluting bone cement spacer followed by reimplantation are two methods often used to treat infected patients with mixed outcomes. Like bone cement, ultra-high molecular weight polyethylene (UHMWPE) can also be used as a carrier for antibiotics. Recently, we demonstrated that vancomycin and rifampin can be delivered from UHMWPE implants at therapeutic levels to eradicate Staphylococcus aureus biofilm in a lupine animal model. There are regulatory challenges in translating these types of combination devices to clinical use. Last year, at this meeting, we presented the preliminary pre-clinical testing for a temporary UHMWPE spacer containing gentamicin sulfate as a first step towards clinical use. Since then, we carried out a survey among the Knee Society membership about their preference for spacer use in two-stage revision surgery and found that 43% prefer to use a CoCr femoral component on an all-poly cemented tibial insert, 22% prefer bone cement spacers molded in the OR, 20% prefer static bone cement spacers, and 14% prefer pre-formed bone cement spacers. We modified our implant design based on the majority's preference for a total knee system, rather than bone cement spacers, in the temporary two-stage approach. In this study, we explored the effect of gentamicin sulfate (GS) elution from UHMWPE/GS tibial inserts on bacterial colonization on CoCr surfaces. Methods. We characterized the gentamicin sulfate (GS) particles with scanning electron microscopy (SEM). We molded UHMWPE/GS powder blends and characterized the morphology using SEM and Energy Dispersive X-Ray Spectroscopy (EDS). We submerged samples of molded UHMWPE/GS in buffered phosphate solution (PBS) at 37°C and quantified the extent of GS elution into PBS with a method described by Gubernator et al. using o-phthaladehyde (OPA) [1]. Under basic conditions, OPA reacts with primary amino groups to form fluorescent complexes. Since gentamicin is the only source of such amino acids in our elution samples, the number of fluorescent complexes formed is directly proportional to the amount of gentamicin in the sample. Using this method, we could quantify gentamicin elution by measuring sample fluorescence post OPA-reaction. We used a plate reader to excite the fluorescent complexes formed in the OPA reaction and measured the resulting emission at wavelengths of 340 nm and 455 nm, respectively. We also quantified the effect of the standard cleaning protocol (heated sonication in alkaline water and alcohol) used to clean UHMWPE implants on subsequent GS elution from UHMWPE/GS samples using the OPA method. We used agar diffusion tests to characterize antibacterial properties of UHMWPE/GS samples after cleaning. For these tests, we collected eluents collected from UHMWPE/GS and gentamicin-impregnated bone cement (BC/GS) following 1, 2, 3, and 4 weeks of elution, and tested against S. aureus (ATCC 12600). We used the “daughter cells” method developed by Bechert et al. to assess anticolonizing properties of UHMWPE/GS [2,3]. We also characterized the colonization of bacteria on CoCr surfaces in the presence of GS eluting from UHMWPE/GS test samples. For this we modified a Pin-on-Disc (PoD) wear tester: An UHMWPE/GS pin and UHMWPE pin (control) articulated against an implant-finish CoCr disc with Tryptic Soy Broth containing S. Aureus as the lubricant. After 18 hrs, we rinsed the articular surfaces of the pin and disc and stamped them onto Agar gel to transfer any adherent bacteria. We incubated the Agar plate overnight such that adherent bacteria proliferated and became visible. Results. SEM characterized the GS particles as hollow spheres (Fig 1a). These formed small groups of agglomerated domains at the virgin resin boundaries of UHMWPE after molding (Fig 1b). Sulfur signature from the EDS analysis identified the agglomerated domains as GS particles (Fig 2). Elution of GS started with an initial burst and was followed by steady elution up to 12 weeks (Fig 3). Cleaning reduced the initial burst GS elution; and the elution remained unchanged after 2 days (Fig 4). The agar diffusion test showed simmilar inhibition zones for the eluents collected from UHMWPE/GS and BC/GS, suggesting that these samples yield similar antibacterial activity against S. aureus (Fig 5). UHMWPE/GS demonstrated pronounced anticolonizing properties, effectively mitigating the proliferation of S. aureus “daughter” cells. Anticolonizing activity of Palacos R+G was not significantly different when compared with UHMWPE/GS. The PoD test showed little-to-no colonization of CoCr surfaces in the presence of UHMWPE/GS pins, indicative of excellent antibacterial properties of UHMWPE/GS against S. aureus. Conclusion. SEM and EDS has allowed us to visualize domains of gentamicin sulfate particles in UHMWPE. Our OPA method has greater precision than traditional agar-well diffusion methods of measuring gentamicin concentration and showed that gentamicin sulfate-loaded UHMWPE elutes at the same rate as Palacos R+G. Pin-on-disc experiments and the daughter cell method both confirmed that these two materials have similar anticolonization abilities. We also found that using the standard cleaning protocol for UHMWPE orthopedic implants decreased the burst of gentamicin eluting from UHMWPE, but after 2 days, it had no effect compared to uncleaned UHMWPE/GS. Finally, we found that UHMWPE/GS can reduce the colonization of bacteria on CoCr. UHMWPE/GS continues to be a promising material for treating PJI. For figures, tables, or references, please contact authors directly

Introduction. Ultra-high molecular weight polyethylene (UHMWPE) can provide local sustained delivery of therapeutics. 1,2. For example, it can deliver analgesics to address post-arthroplasty pain. 2. Given that several analgesics, such as bupivacaine (anesthetic) and tolfenamic acid (NSAID), were shown to possess antibacterial activity against Staphylococci, we hypothesize that analgesic-loaded UHMWPE can also yield antimicrobial effects, preventing the development of periprosthetic joint infections. Methods. Bupivacaine and tolfenamic acid were incorporated into UHMWPE via phase-separated compression molding. Drug release from the prepared samples was measured using high-performance liquid chromatography. Antibacterial studies of the obtained materials were conducted against methicillin-sensitive, and methicillin-resistant S. aureus, as well as S. epidermidis. Time-kill curves were obtained to characterize antimicrobial activity against planktonic bacteria. The dynamics of bacterial adhesion were assessed to characterize antibiofilm activity. Scanning electron microscopy (SEM) was used to visualize adherent bacteria. Anticolonizing activity of the tested materials was characterized using the “daughter cell” method as outlined elsewhere. 3. Cytotoxicity profile of drug-loaded UHMWPEs was evaluated using MG-63 osteoblast cell line. Results. The bupivacaine release rate generally increased with increasing drug loading (e.g. a model knee implant loaded with bupivacaine would release ca. 15–500 mg over 24 hours). While also proportional, drug release from UHMWPE loaded with tolfenamic acid was much lower. The bacterial viability curves showed that bupivacaine-loaded UHMWPE possessed moderate antibacterial activity against planktonic MSSA, MRSA, and S. epidermidis, slowing bacteria proliferation by up to 70%. Bupivacaine-loaded UHMWPE also mitigated biofilm formation and development during the initial culture period. SEM images confirmed the observed antibiofilm effect (Fig. 1). Tolfenamic acid-loaded UHMWPE allowed proliferation of planktonic bacteria. At the same time, these materials showed pronounced dose-dependent anticolonizing activity against tested strains, providing 3-log reduction of “daughter” cells. Bupivacaine- and tolfenamic acid-loaded UHMWPEs showed little-to-no cytotoxicity against osteoblasts. Discussion & Conclusions. We demonstrated for the first time that bupivacaine-loaded UHMWPE possesses dose-dependent antibacterial properties against planktonic and adherent MSSA, MRSA, and S. epidermidis – pathogens commonly associated with periprosthetic joint infections. Pronounced anticolonizing activity was evident for tolfenamic acid-loaded UHMWPE. Due to the low solubility of tolfenamic acid, the material's antibacterial effect against planktonic bacteria was lower. These results demonstrate that analgesic-loaded UHMWPE, used as a tool in multimodal pain management, can also yield antibacterial effects, opening an entirely new avenue for providing post-arthroplasty antibacterial prophylaxis. This pioneering approach has a potential to reduce patients' morbidity and mortality after arthroplasty. For any tables or figures, please contact the authors directly

Infection remains as one of the major challenges of total joint surgery. One-stage irrigation, debridement and reimplantation or two-stage revision surgery with a temporary implantation of antibiotic eluting bone cement spacer followed by reimplantation are two methods often used to treat infected patients with mixed outcomes. Like bone cement, ultra-high molecular weight polyethylene (UHMWPE) can also be used as a carrier for antibiotics. Recently, we demonstrated that vancomycin and rifampin can be successfully delivered from UHMWPE implants at therapeutic levels to eradicate Staphylococcus aureus biofilm in a lupine animal model. There are regulatory challenges in translating these types of combination devices in to clinical use. One approach is to follow a stepwise strategy, with the first step of seeking clearance for a temporary UHMWPE spacer containing gentamicin sulfate. In this study, we explored the effect of gentamicin sulfate (GS) content in UHMWPE on GS elution rate and antimicrobial activity against methicillin-sensitive S. aureus(MSSA). We also assessed the effect of spacer fabrication on the activity of gentamicin sulfate. We prepared and consolidated UHMWPE/GS blends in varying concentrations. After consolidation, we fabricated test samples with surface area (350mm2) to volume (300mm3) ratio of 1.2 for elution in 1.5ml phosphate buffered saline at body temperature for up to six months and quantified eluted GS content using liquid chromatography – mass spectrometry (LCMS). We assessed the antibacterial activity of the obtained samples in vitro against various concentrations of MSSA (103–106 CFU/ml). Furthermore, we quantified the probability of bacterial colonization of UHMWPE impregnated with GS compared to GS containing bone cement. We assessed any detectable changes in activity of eluted GS caused by spacer fabrication by screening m/z peaks of GS isomers in mass spectra obtained from LC-MS. Gentamicin sulfate activity was not compromised by the elevated temperature and pressure used during spacer fabrication. Elution rate of GS increased with increasing GS content in the blends studied. At comparable elution rates, the GS-loaded UHMWPE was either equivalent or better in terms of antibacterial and anticolonization properties when compared with gentamicin containing bone cement. GS-impregnated UHMWPE is a promising material for temporary spacers

Currently, between 17% of patients undergoing surgery for adult spinal deformity experience severe instrumentation related problems such as screw pullout or proximal junctional failure necessitating revision surgery. Cables may be used to reinforce pedicle screw fixation as an additive measure or may provide less rigid fixation at the construct end levels in order to prevent junctional level problems. The purpose of this study is to provide insight into the maximum expected load during flexion in UHMWPE cable in constructs intended for correction of adult spine deformity (degenerative scoliosis) in the PoSTuRe first-in-man clinical trial. Following the concept of toppinoff, a new construct is proposed with screw/cable fixation of rods at the lower levels and standalone UHMWPE cables at the upper level (T11). A parametric FE model of the instrumented thoracolumbar spine, which has been previously validated, was used to represent the construct. Pedicle screws are modeled by assigning a rigid tie constraint between the rod and the lamina of the corresponding spinal level. Cables are modeled using linear elastic line elements, fixing the rod to the lamina medially at the cranial laminar end and laterally at the caudal laminar end. A Youngs modulus was assigned such that the stiffness of the line element was the same as that of the cable. An 8 Nm flexion moment was applied to the cranial endplate. The maximum value of the force in the wire (80 N) is found at the T11 (upper) level. At the other levels, forces in the cable are very small because most of the force is carried by the screw (T12) or because the wires are force shielded by the contralateral and adjacent level pedicle screws (L2, L3). The model provides first estimates of the forces that can be expected in the UHMWPE cables in constructs for kyphosis correction during movement. It is expected that this approach can help in defining the number of wires for optimal treatment

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. Orthopedic implants are subject to wear and release ultra-high molecular weight polyethylene (UHMWPE) debris. Analysis of UHMWPE wear particles is critical in determining the safety and effectiveness of novel orthopedic implants. Complete digestion of periprosthetic tissue and wear fluid is necessary to ensure accurate morphological and quantitative particle analysis. Acid digestion methods are more effective than enzymatic and base digestion approaches [Baxter+ 2009]. However, optimal digestion times, quantity, and type of acid are unclear for particle isolation. In addition, imaging and analysis techniques are critical to ensure accurate reporting of particle characteristics. Here, we 1) compared the efficacy of three acid-based digestion methods in isolating particles from a) bovine serum and b) animal/human tissue, and 2) analyzed the effects of imaging location on particle quantity/morphology results. Methods. 1a) UHMWPE (GUR 150) particles were generated by Mode I knee wear testing for 1 million cycles in bovine serum. Serum was digested in one of four solutions: 12.2M HCl, 15.8M HNO. 3. , a 1:1 volume ratio of HNO. 3. :HCl (aqua regia), or filtered H. 2. O (control). The serum:solution volume ratio was 1:5 [Niedzwiecki+ 2001, ISO 17853:2011]. Digestion occurred for 60min on a stir plate at 60°C. Each digest was combined with MeOH at a 1:5 digest:MeOH volume ratio and filtered using a 100 nm polycarbonate membrane. The particle-containing membranes were imaged (12 images/membrane) using scanning electron microscopy (SEM) to determine particle characteristics, including quantity, equivalent circular diameter (ECD) and aspect ratio (AR). 1b) Based on 1a, HNO. 3. was used to digest porcine and human tissue at concentrations of 1:40, 1:60, or 1:80 tissue:HNO. 3. volume ratios for either 1, 12, or 24 hours, followed by SEM analysis. 2) Particle characteristics were compared at nine locations (20 images/location) across a particle-containing membrane to determine the effects of imaging location. Results. 1a) HNO. 3. and aqua regia methods successfully digested the bovine serum, whereas the HCl and H. 2. O methods were unsuccessful (Fig.1A). Comparing HNO. 3. and aqua regia groups, particle characteristics and ECD frequency distribution were nearly identical (Fig.1B). 1b) Nitric acid did not fully digest porcine or human tissues. 2) Similar particle characteristics were observed in all nine locations analyzed across the polycarbonate membrane. The particle quantity, ECD, and AR for a representative center vs. intermediate location were 808 vs. 780 particles, 0.33±0.28 vs. 0.35±0.29 µm, and 1.57±0.56 vs. 1.51±0.4, respectively (Fig.2). Conclusions. Nitric acid and aqua regia are capable of digesting bovine serum using low quantities of acid for short duration, allowing precise analysis of UHMWPE particle debris from orthopedic implants. However, further optimization of digestion techniques for animal/human tissue is warranted. In addition, an accurate representation of particle distribution can be achieved without analyzing hundreds of images, because membrane location does not strongly influence particle results. Finally, ASTM F1877-16 – Standard Practice for Characterization of Particles – could benefit from adding software-based automated particle characterization as an optional method. An automated approach that uses k-means clustering image segmentation to identify particles and computer vision tools to extract relevant morphological features is under development and validation

Introduction. Radiation cross-linking of ultrahigh molecular weight polyethylene (UHMWPE) has reduced the in vivo wear and osteolysis associated with bearing surface wear (1), significantly reducing revisions associated with this complication (2). Currently, one of the major and most morbid complications of joint arthroplasty is peri-prosthetic infection (3). In this presentation, we will present the guiding principles in using the UHMWPE bearing surface as a delivery device for therapeutic agents and specifically antibiotics. We will also demonstrate efficacy in a clinically relevant intra-articular model. Materials and Methods. Medical grade UHMWPE was molded together with vancomycin at 2, 4, 6, 8, 10 and 14 wt%. Tensile mechanical testing and impact testing were performed to determine the effect of drug content on mechanical properties. Elution of the drug was performed in phosphate buffered saline (PBS) for up to 8 weeks and the detection of the drug in PBS was done by UV-Vis spectroscopy. A combination of vancomycin and rifampin in UHMWPE was developed to address chronic infection and layered construct containing 1 mm-thick drug-containing UHMWPE in the non-load bearing regions was developed for delivery. In a lapine (rabbit) intra-articular model (n=6 each), two plug of the layered UHMWPE construct were placed in the trochlear grove of the rabbit femoral surface and a porous titanium rod with a pre-grown biofilm of bioluminescent S. Aureus was implanted in the tibia. Bioluminescent imaging was employed to visualize and quantify the presence of the bacteria up to 3 weeks. Results and Discussion. Increasing drug content decreased both the ultimate tensile strength (UTS) and the impact toughness of vancomycin-containing UHMWPE (Figure 1). Elution data and structural analysis suggested that a percolation threshold was reached at above 6 wt% drug in UHMWPE, which resulted in sustained drug delivery above the minimum inhibitory concentration (MIC; 1 mg/ml) for up to 8 weeks (Figure 2). The layered constructs implanted in rabbits were able to eradicate all detectable bacteria from the biofilm on the titanium surfaces implanted on the counterface (Figure 3), suggesting clinically relevant efficacy. Significance. To our knowledge, this is the first study showing the design and efficacy of an antibiotic-eluting UHMWPE bearing surface. Such a device has the potential of reducing all two-stage revisions to single-stage treatment with load-bearing components, enhancing the mobility and quality of life for the patients and reducing the cost of infection treatment in arthroplasty. For figures/tables, please contact authors directly.

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. Dl-α-Tocopherol (VE)-blended non-crosslinked UHMWPE has been developed as a bearing surface material for knee prostheses due to the radical scavenging capabilities of vitamin E and has demonstrated a low wear rate in knee simulator testing [1,2]. In previous our study, VE-blended, crosslinked UHMWPE has demonstrated a low wear rate in hip simulator testing [3, 4]. As the radical scavenging capabilities also reduce the crosslinking degree of the material, multiple dose crosslinking has been investigated. However, these crosslinked UHMWPE materials may have different mechanical properties, as each crosslinking process, especially the annealing condition, is different. Additionally, there is little information about VE-blended, crosslinked UHMWPE with different annealing conditions. In this study, the effect of annealing temperature was investigated with regard to tensile strength, crosslink density, and crystallinity of VE blended, crosslinked UHMWPE. Method. VE blended samples were manufactured via direct compression molding following the blending of UHMWPE resin powder (GUR1050, Ticona Inc.) with VE (dl-α-tocopherol, Eisai Co. Ltd.) at 0.3wt%. The virgin samples were derived similarly, but without the addition of VE. Both materials underwent crosslinking by irradiation via a 10MeV electron beam at 300kGy and were then heat treated at several temperatures (25, 80, 110, 130 and 150 °C) for 24 hours. Gel content, which can be interpreted as cross-link density, was determined by measuring the weight of the samples before and after soaking in decahydronaphthalene at 150 °C for twelve days. Tensile tests were carried out following JIS K 7113, with the cross head speed set at 50 mm/min. Crystallinity was determined by using DSC and integrating over the enthalpy curve from 80 to 150 °C and normalizing with the enthalpy of melting for 100% crystalline polyethylene. Result. Fig. 1 shows the gel content of UHMWPE samples after crosslinking. Raising the annealing temperature caused an increase in the gel content regardless the VE content. Additionally, among samples with the same annealing temperature, VE samples had the lower gel content. Fig. 2 shows the yield strength of UHMWPE samples. Higher annealing temperature decreased the yield strength, and increased elongation. Fig. 3 shows the crystallinity of each UHMWPE sample. Higher annealing temperature decreased the crystallinity of UHMWPE. Discussion. In this study, the effect of annealing temperature on the mechanical properties of crosslinked UHMWPE was investigated. The results indicated that a greater volume of crystalline UHMWPE melted and reformed at the higher annealing temperatures. This was thought to occur due to the fact that UHMWPE consists of a range of different molecular weight chains, allowing for melting below 135°C. Therefore, the crystallinity and crosslink density changed for each annealing temperature. The annealing is a simple but effective method for designing the crystallinity and crosslinking of UHMWPE

Introduction. UHMWPE articulating against PEEK-OPTIMA® has the potential for use as a novel bearing couple in joint arthroplasty due to its potentially low wear rates and the bioinertness of its wear debris. The aim of this study was to investigate the role of protein in the lubricant on the wear of UHMWPE articulating against PEEK at both room and physiological temperature. Methods. The wear of GUR1020 UHMWPE pins articulating against PEEK plates (R. a. ∼0.06µm) was compared to highly polished cobalt chrome plates (R. a. <0.01µm) in a 6-station multi-axial pin-on-plate rig using kinematics to replicate those in total knee arthroplasty. Tests were carried out at either ∼20°C or ∼36°C and wear was investigated under varying concentrations of bovine serum (0, 25 or 90%). Studies were carried out for 1 Million cycles with wear of the UHMWPE pins assessed gravimetrically using unloaded soak controls to compensate for moisture uptake. Statistical analysis was carried out using ANOVA with significance taken at p<0.05. Results. Figure 1 shows wear factors for the UHMWPE pins. In 0% serum, the wear of UHMWPE against both PEEK and cobalt chrome tested at room and physiological temperatures was very low. When lubricated with 25% serum and tested at room temperature as per standard practice at Leeds, the wear of UHMWPE against cobalt chrome was comparable to previously published data (2.13×10. −7. mm. 3. /Nm) and the wear of UHMWPE articulating against PEEK was 3.53×10. −7. mm. 3. /Nm. At physiological temperatures, the wear of UHMWPE against cobalt chrome was similar to tests at room temperature but against PEEK, there was a significant (p=0.017) decrease in wear factor [1]. The wear of UHMWPE against cobalt chrome was significantly (p=0.003) higher when tested in 90% serum compared to 25% serum at room temperature but this effect was not seen in UHMWPE articulating against PEEK (p=0.38). Testing at elevated temperature in 90% serum significantly (p=0.007) decreased the wear of UHMWPE against cobalt chrome and a deposition, likely to be protein, was evident on the surface of the plates. However, against PEEK, there was no significant difference in wear under the different temperature conditions. Discussion. In pin-on-plate tests of UHMWPE against smooth metal counterfaces, the low wear rate and polymer deposition in tests lubricated with water has previously been observed. A similarly low wear rate has now been observed for UHMWPE against PEEK. Water does not produce adequate boundary lubrication. At 25% and 90% serum and varying temperatures the wear behaviour of UHMWPE against PEEK is not the same as UHMWPE against cobalt chrome. There may be a number of factors contributing to these differences, including surface topography, protein precipitation, protein deposition, differing wear mechanisms and lubrication regimes. For example, UHMWPE-PEEK is a higher friction bearing couple than UHMWPE-CoCr and when tested at elevated temperatures, frictional heating at the bearing surfaces may accelerate protein precipitation and adsorption of protein onto the articulating surfaces which may affect wear. This study shows that testing under different lubricant and environmental conditions can have a significant effect on wear