As a technique, cross-linking of ultra-high molecular weight polyethylene has been used to decrease the wear of these bearing surfaces since the 1970s1-3. Clinical adoption of these polyethylenes began with the current, widely used formulations of highly cross-linked polyethylene. These formulations were introduced for use in total joint replacements beginning in 1998 to address the long-term problem of periprosthetic osteolysis4-8. Clinical follow-up studies have shown that these materials have significantly lower in vivo wear than conventional ultra-high molecular weight polyethylene and, to date, few occurrences of periprosthetic osteolysis have been reported9-14. These materials have two advantages over conventional ultra-high molecular weight polyethylene: they are highly cross-linked with high-dose irradiation used to provide wear resistance, and they are oxidatively stabilized by postirradiation melting or annealing to quench the free radicals formed during irradiation, which are responsible for long-term oxidative degradation of the mechanical properties of ultra-high molecular weight polyethylene15,16. However, stabilization with postirradiation melting results in a further decrease in the fatigue strength in addition to that due to cross-linking17. Because of this fatigue strength decrease, there is concern about the increased risk of fracture in adverse conditions such as high-demand applications or malpositioned implants18,19.
This concern has prompted investigations into alternative methods of reducing the oxidative potential of free radicals by heat annealing20 or by stabilizing them with an antioxidant additive21. However, heat-annealed acetabular liners were typically terminally gamma-sterilized, which increased the concentration of residual free radicals in the material, and associated oxidation has been observed in explanted components16. An alternative approach, stabilization of the free radicals with vitamin E, has been reported to improve oxidation resistance of irradiated ultra-high molecular weight polyethylene under normal and aggressive aging conditions in vitro22. While this material is a promising alternative to currently used highly cross-linked ultra-high molecular weight polyethylenes, we know of no report of its clinical performance. Our formulation of vitamin-E-doped cross-linked polyethylene was introduced into clinical use in total hip arthroplasty in June 2007 at Massachusetts General Hospital in Boston, Massachusetts, after clearance from the U.S. Food and Drug Administration.
In currently used implant components, vitamin E is incorporated in radiation-cross-linked ultra-high molecular weight polyethylene by postirradiation diffusion and homogenization23. Since most of it is not covalently bound to the ultra-high molecular weight polyethylene molecules, it is likely that some vitamin E is released in vivo. We hypothesized that, after elution from ultra-high molecular weight polyethylene, vitamin E associated with a carrier would not cause substantial inflammation in the joint and that, in an implant-like situation in a small-animal model, the vitamin E eluted from the ultra-high molecular weight polyethylene would cause no adverse local tissue response. We also hypothesized that, in a large-animal study, vitamin-E elution would not hinder the initial osseous ingrowth, an important factor in the success of a total hip replacement.
To determine the local tissue effects of free vitamin E and vitamin E eluted from ultra-high molecular weight polyethylene implants into the joint space, we conducted the following studies in relevant animal models: We injected solubilized vitamin E intra-articularly in rabbits to determine the effect of free vitamin E; we implanted subcutaneous plugs of vitamin-E-doped, highly cross-linked ultra-high molecular weight polyethylene to determine the effect of vitamin E eluted from ultra-high molecular weight polyethylene on the local tissue; and we performed canine total hip replacement using vitamin-E-doped, highly cross-linked ultra-high molecular weight polyethylene acetabular liners to examine the soft-tissue response and bone ingrowth in a clinically relevant model.
In the first study to examine the biological response to vitamin E, synthetic vitamin E and solubilized synthetic vitamin E were injected into the knee joints of New Zealand White rabbits. All animal studies were conducted in accordance with best practices established by our Institutional Animal Care and Use Committee. Synthetic vitamin E was used as received from the manufacturer (natural vitamin E was D-a-tocopherol [E1490; ADM, Decatur, Illinois] and synthetic vitamin E was D,L-a-tocopherol [E307; Roche, Basel, Switzerland] at a density of 0.95 g/mL) after sterilization by gamma radiation (STERIS Isomedix, Northborough, Massachusetts) in 20-mL pharmaceutical vials in gas-permeable packaging. Solutions of Tween 80 (Sigma, St. Louis, Missouri) or emulsions of Tween 80 and ethanol were used to prepare intra-articular injections of vitamin E. Tween 80 and vitamin E were separately heated to 60°C. The Tween 80 and vitamin E were then mixed and diluted with solvent (water or a water-ethanol solution) to a final concentration of 5 mg/mL (calculated with use of the density of a-tocopherol as 0.95 g/mL). Solutions contained 15 weight percent (wt%) of Tween 80 and emulsions contained 0.25 wt% of Tween 80 and 6 wt% of ethanol. After mixing the components together, the solutions and emulsions were boiled under reflux for several hours to stabilize the mixture. The solutions and emulsions were then cooled and injected into 20-mL pharmaceutical vials with septa through a 19-gauge needle. These vials as well as vials containing control carrier solutions were then placed in gas-permeable packaging and sterilized by gamma irradiation at 25 to 40 kGy (STERIS Isomedix).
Skeletally mature New Zealand White rabbits were divided into three groups. One group received 10 µL of synthetic vitamin E (10 mg of a-tocopherol) (six rabbits), one received 2 mL of the 5-mg/mL vitamin-E solution (six rabbits), and one received 2 mL of 5-mg/mL vitamin-E emulsion (nine rabbits). All preparations were injected through the lateral side of the knee with use of a 20-gauge needle after the needle punctured the capsule. All rabbits receiving the synthetic vitamin E and vitamin-E solution were killed at two weeks, three of the nine in the emulsion group were killed at two weeks, and the remaining six were killed at twelve weeks. The contralateral knee served as an internal control, receiving the same volumes of sterile saline solution or carrier solution.
In the second study, vitamin-E-doped ultra-high molecular weight polyethylene plugs were inserted into dorsal subcutaneous pouches of New Zealand White rabbits. To make the plugs, GUR1050 ultra-high molecular weight polyethylene bar stock (Orthoplastics, Lancashire, United Kingdom) was first annealed below the melting point to minimize thermal stresses in the subsequent processing steps. The bar stock was then cut into 4-cm-thick sections and was packaged in double layers of aluminum packaging in a vacuum. Packaged stock was irradiated to 100 kGy with use of double-sided electron beam irradiation with a 10-MeV source (Iotron, Vancouver, British Columbia, Canada). Cylindrical plugs (1 cm in diameter and 3.75 cm in length) were machined from irradiated stock. Vitamin E was incorporated into these irradiated plugs by soaking in vitamin E at 120°C for five hours under argon purge. The plugs were then taken out of the vitamin-E bath and cooled to approximately room temperature. Excess vitamin E was wiped off the surfaces with clean gauze pads. The vitamin-E concentration of the plugs was subsequently homogenized at 120°C for sixty-four hours under argon purge. Soaked and homogenized plugs were then cleaned by first washing in a mild detergent solution and then by washing in a nitric acid solution. The plugs were packaged in two layers of gas-permeable packaging in sets of four and were sterilized by gamma irradiation to 25 to 40 kGy (STERIS Isomedix). Control plugs were machined from nonirradiated ultra-high molecular weight polyethylene stock with the same dimensions and were cleaned and sterilized in the same manner without any vitamin-E treatment.
Two groups of five New Zealand White rabbits received eight sterile ultra-high molecular weight polyethylene implants placed subcutaneously, four on each side in the dorsal lumbar region. Implants on the right side contained vitamin E. The first group of five rabbits was killed at two weeks, the second group of five rabbits was killed at twelve weeks, and the surrounding soft tissue was harvested for histological analysis. The vitamin-E content in the explanted ultra-high molecular weight polyethylene plugs was determined by identifying an infrared spectroscopy peak at 1262 cm-1 (in the integration range between 1245 cm-1 and 1275 cm-1). Samples were fixed in formalin, embedded in paraffin, sliced into 4-µm slices, and stained with hematoxylin and eosin. Stained samples were evaluated by a pathologist who was blinded to the experimental conditions. Histological evaluation assessed the pathologic changes of the anatomic structures associated with the implanted materials. This included assessment of synoviocytes, the composition of the subsynovial tissue, fibrin deposition, reactive fibrous tissue, the presence of inflammation and specific types of inflammatory cells, the presence of foreign material, and the status of articular cartilage, subchondral bone, and joint capsule. This study was nonrandomized and unblinded.
In addition to the rabbit studies, a canine model of total hip replacement was used to study the effect of in vivo elution of vitamin E from acetabular liners on bone ingrowth. Three groups of ultra-high molecular weight polyethylene acetabular liners were prepared. The control group consisted of irradiated and remelted liners, and the two experimental groups consisted of irradiated and vitamin-E-doped ultra-high molecular weight polyethylene liners, one with high surface vitamin-E concentration and another with uniform, lower vitamin-E concentration through the thickness of the components. GUR1050 ultra-high molecular weight polyethylene bar stock (Orthoplastics) was first annealed below the melting point to minimize thermal stresses in the subsequent processing steps. The bar stock was cut into 4-cm-thick sections and packaged in double layers of aluminum packaging in a vacuum. Packaged stock was irradiated to 100 kGy with use of double-sided electron beam irradiation with a 10-MeV source (Iotron). One bar was machined into implant preforms, oversized by 2 mm on both the articular side and backside. These irradiated preforms were soaked in vitamin E at 120°C for 2.5 hours under argon purge. The preforms were then taken out of the vitamin-E bath and cooled to approximately room temperature. Excess vitamin E was wiped off the surfaces with clean gauze pads. The vitamin-E concentration of the preforms was subsequently homogenized at 120°C for forty hours under argon purge. Soaked and homogenized preforms were then machined into the final acetabular liners by machining 2 mm from the surface on both sides. Liners with uniform vitamin-E concentration profiles were made in the same way with vitamin-E incorporation at 120°C for forty-five minutes and homogenization at 130°C for ninety-six hours.
Liners in the control group were machined directly from irradiated bar stock, which had been subsequently melted under vacuum at 170°C. All liners were cleaned by first sonicating in a mild detergent solution followed by washing in a nitric acid solution and drying. They were packaged individually in aluminum foil packaging in a vacuum and further packaged in gas-permeable packaging and sterilized by gamma irradiation to 25 to 40 kGy (STERIS Isomedix).
Vitamin-E-doped liners with high surface concentration contained a mean (and standard deviation) of 1.4 ± 0.05 wt% of vitamin E (mean, 94 ± 3 mg), and uniform vitamin-E liners contained a mean of 0.7 ± 0.07 wt% of vitamin E (mean, 46 ± 5 mg). Vitamin-E concentration profiles were determined with use of Fourier transform infrared spectroscopy (FTIR, FTS155/UMA500; Bio-Rad, Cambridge, Massachusetts) on thin sections (approximately 150 µm) cut with use of a sledge microtome (model 90-91-1177; LKB-Produkter AB, Bromma, Sweden). Infrared spectra were collected from one edge of the sample to the other, spanning two opposite free surfaces of the ultra-high molecular weight polyethylene in 100-µm intervals, with each spectrum recorded as an average of thirty-two individual scans. The infrared spectra were analyzed to calculate a vitamin-E index as the ratio of the areas under the a-tocopherol absorbance at 1262 cm-1 (peak maximum) and the polyethylene skeletal absorbance at 1895 cm-1 (peak maximum).
Twenty-one mature, male dogs were selected after assessment for skeletal maturity and radiographic templating to ensure the proper sizing of the femoral canal. All animals received on the right side a cementless total hip replacement with a beaded cobalt-chromium porous surface. Seven animals received control liners, seven received vitamin-E-doped liners with high surface concentration, and seven received uniform vitamin-E liners. After the dogs were placed under general anesthesia, a posterior approach was used, and an established, standard total hip replacement procedure was followed with use of porous titanium components24. After surgery, the animals were allowed unrestricted weight-bearing activity and were exercised daily. Three months after surgery, the animals were killed and the hips, femora, and surrounding soft tissue were harvested en bloc. From this point on, the experimental group was blinded to the evaluator. The entire pseudocapsule that had formed around the joint was excised, fixed in formalin, and processed for hematoxylin and eosin staining. In select cases, fresh-frozen pseudocapsule samples were taken prior to formalin fixation for oil-red-O staining.
Contact radiographs of the right hip containing the implant-bone composite were made. The femoral implant-bone composite was cut with use of a high-speed diamond saw (DoALL, Wheeling, Illinois) at 8 cm and 4 cm distal to the implant flange. The acetabular shell and surrounding acetabular bone as well as the proximal 4 cm of the femoral implant-bone composite were dehydrated in graded ethanol and acetone for six weeks, embedded in polymethylmethacrylate for six weeks, and allowed to harden for six to eight weeks. After baking for one hour at 90°C to fully harden, the embedded implant-bone composite was sectioned into 1-mm sections with use of the high-speed diamond saw.
Representative sections were polished and gold-coated for backscatter scanning electron microscopy (JSM-5910; JEOL, Peabody, Massachusetts). Images were taken as contiguous rectangular fields at 43× magnification. Image analysis was performed with use of ImageJ 1.36b software (National Institutes of Health, Bethesda, Maryland) to quantify the amount of bone ingrowth in the porous layer of the implants. Bone ingrowth was defined as the area occupied by bone divided by the total area occupied by bone, metal, and void space. Bone density was defined as area occupied by bone divided by the initial void space25. One representative section per sample was selected for histological evaluation. Sections were ground to a thickness of 100 to 150 µm with use of a rotary sander and increasing grits of abrasive paper. After polishing with 400-grit paper, the sections were secured to a slide with use of an adhesive (M-Bond 200 adhesive kit; M-Line Accessories, Vishay Micro-Measurements, Raleigh, North Carolina). Samples were then stained with hematoxylin and eosin for histological observations.
For all rabbit and canine studies, the gross appearance of the joint or subcutaneous pouch was noted as well as the characteristics of the joint fluid. Sections of knee capsule, subcutaneous pouch, and hip pseudocapsule were fixed in formalin, embedded in paraffin, sliced into 4-µm slices, stained with hematoxylin and eosin, and evaluated by a pathologist who was blinded to the experimental conditions.
Statistical Methods
A one-way analysis of variance was done to compare the average percent bone ingrowth and average percent bone density between the three groups of liners in the canine study. Standardized effect sizes were calculated by dividing the difference between the average values of the study groups and the control group and dividing by the standard deviation of the control group. Patterns in gross or histological observations of the canine pseudocapsule or rabbit subcutaneous pouch were compared between groups with use of a Fisher exact test for binomial proportions on the basis of the small sample sizes.
Source of Funding
There were no external funding sources for these studies.
Vitamin-E Injections and Vitamin-E-Doped Ultra-High Molecular Weight Polyethylene Plugs in a Rabbit Model
For the first injection group receiving synthetic vitamin E, gross observations of the vitamin-E-injected knees showed signs of inflammation, vascularization, and "granuloma-like" aggregates beneath the synovial lining in the region of the injection site. The joints also contained 1 to 3 mL of viscous fluid. The presence of the fluid was thought to be a result of persistent irritation of the knee as all cultures were negative. The contralateral, control knees had a normal appearance with no accumulation of joint fluid. Histological features of the vitamin-E-injected joint capsule tissue revealed granulation tissue with acute and chronic inflammation, surface fibrin deposition, and cellular debris. The synoviocytes lining the capsule were either destroyed or covered by a fibrinous exudate. The subsynovial tissue was thickened and contained numerous round, clear void spaces of varying size. These spaces were associated with numerous macrophages with scattered eosinophils, lymphocytes, plasma cells, and fewer numbers of neutrophils (Fig. 1). Some of the macrophages had flocculent eosinophilic material within their cytoplasm. Beneath the inflammatory tissue was reactive fibrosis. The histological analysis of the saline solution controls revealed normal synovial tissue.
The results for the injection of solubilized vitamin E were consistent regardless of time in situ or solvent used. The synovial tissue had a normal gross appearance at harvest, and there were no signs of inflammation or a surface exudate. Histologically, the vitamin-E-injected synovium had a normal appearance and had a one to two-cell-layer-thick lining of synoviocytes (Fig. 2). The synoviocytes were viable and contained oval nuclei and eosinophilic cytoplasm with no evidence of exogenous material. The synovial tissue of all control knees had the same appearance.
After subcutaneous implantation of the polyethylene plugs, both vitamin-E-doped and control plugs were encapsulated by a synovial-like membrane as has been reported in similar studies26. Infrared spectroscopy showed a small amount of vitamin E was eluted from the surface of plugs. At two weeks, the membrane surrounding both the control and vitamin-E-impregnated polyethylene plugs contained numerous macrophages and reactive fibroblasts (Fig. 3). At twelve weeks, the encapsulating tissue lacked inflammation or contained few blood vessels, and the actual membrane consisted of a thin layer of collagenous fibrous tissue lined by several layers of synoviocyte-like cells (Fig. 4). The synoviocyte-like cells were viable and showed no significant alterations of their nuclei or cytoplasm. There was no foreign body reaction associated with either type of plug. There was also no discernable difference in the tissue response to the control polyethylene or the vitamin-E-impregnated implants at either two or twelve weeks after implantation. The vitamin-E profile of the plug after two and twelve weeks in vivo showed a small decrease in vitamin-E index near the surface.
Total Hip Replacement with Vitamin-E-Doped, Highly Cross-Linked Ultra-High Molecular Weight Polyethylene in a Canine Model
Original machining marks were clearly visible under small scratches in all three groups of harvested ultra-high molecular weight polyethylene liners, indicating little polyethylene wear during the twelve-week period. The gross appearance of the harvested soft tissue and the histological findings from the pseudocapsule could be divided into two categories, namely, smooth or papillary. In both categories, the pseudocapsule was approximately 10 to 15 mm in thickness. In the smooth category, the surface adjacent to the joint space had a smooth glistening appearance. In the papillary category, the surface adjacent to the joint space was covered with multiple nodular, grape-like structures (Fig. 5). Each of these appearances was present in the control, vitamin-E-doped with high surface concentration, and uniform vitamin-E groups (two of seven, four of seven, and one of seven, respectively, were in the papillary category). There were no significant group differences (p = 0.59, 0.99, and 0.27 for control versus vitamin-E-doped liners with high surface concentration, control versus uniform vitamin E, and vitamin-E-doped liners with high surface concentration versus uniform vitamin E, respectively).
Histologically, the joint pseudocapsules of all three groups showed similar morphological findings. Their internal surface had an undulating contour that was usually lined by viable, plump synovial-like cells that were one to three cell layers thick (Fig. 6). Immediately beneath these cells, there were fibroblasts that appeared to be randomly oriented and associated with small-caliber blood vessels and extravasated red blood cells. Forming the bulk of the capsule was a thick layer of reactive fibrous tissue in which the fibroblasts were oriented parallel to one another and to adjacent collagen fibers. The collagen fibers were oriented into fascicles that created a basket-weave-like appearance. Additionally, many of the fascicles tended to be oriented parallel to the overlying surface. In many cases, there were small, blunt surface papillae that were composed of a core of connective tissue containing aggregates of blood vessels, numerous fibroblasts, and extravasated red blood cells. Other cores of tissue consisted largely of collagen with scattered fibroblasts and occasional vessels. Another occasional finding was disruption of the surface synovial-like lining and replacement by varying sized aggregates of fibrin platelets and red blood cells. In some of these instances, the fibrin was associated with small shards of bone and round clear voids in the adjacent connective tissue, which also contained hematoidin in some cases. Occasional voids were surrounded by macrophages and overall had the appearance of fat necrosis. In one instance, the voids were present in scar-like tissue and were not associated with hematoidin or other inflammatory cells. In another case, the synovial-like lining was associated with a prominent acute and chronic inflammatory infiltrate as well as fibrin deposition. In a third case, there were similar findings with less inflammation.
The scanning electron microscope images of the acetabular and femoral components showed no significant difference in the measurements of bone ingrowth (p = 0.045) and percent bone density (p = 0.34) among the control, high-surface vitamin-E, and uniform vitamin-E groups (Table I). Histologically, the bone-implant composite sections showed reactive woven bone within the porous layer, reaching the full depth in some areas. There were also areas of fibrous tissue ingrowth with no evidence of macrophage infiltration or active bone resorption.
Osteolysis caused by ultra-high molecular weight polyethylene wear particles is a continuing challenge to the long-term success of total joint replacements5-8. While radiation-cross-linking of ultra-high molecular weight polyethylene has led to reduced wear12-14, it introduces the possibility of oxidative degradation of the mechanical properties of the ultra-high molecular weight polyethylene15-17. To prevent the oxidation of highly cross-linked ultra-high molecular weight polyethylene, the antioxidant vitamin E can be incorporated to stabilize the free radicals that initiate the oxidative cascade. A clinical concern related to the incorporation of vitamin E into ultra-high molecular weight polyethylene components is the possible elution of vitamin E out of the components into the joint space. This study was conducted to determine if pure vitamin E, solubilized vitamin E, and vitamin-E-doped ultra-high molecular weight polyethylene implants introduced into the joint space in relevant animal models caused a negative local tissue reaction or inhibited bone ingrowth. We achieved these aims, determining that pure vitamin E caused a general inflammatory reaction, while solubilized vitamin-E injections and vitamin-E-doped ultra-high molecular weight polyethylene implants showed no discernable differences from control groups in qualitative histological results or quantitative bone-ingrowth measurements.
Prior to these in vivo experiments, in vitro elution tests were conducted to characterize the release of vitamin E from doped ultra-high molecular weight polyethylene bearing components used in total joint replacements27. On the basis of the assumption that the entire weight loss of test liners from a hip simulator study in the presence of third-body particles was due to elution of vitamin E, 17 µg/day would be released27 (approximately 25 IU/day28). This daily dose is much lower than prolonged daily doses of 400 IU that have caused an increase in mortality rates due to all causes in previous studies29,30, leading us to conclude that vitamin-E elution should pose no systemic threat. Intra-articular injections of 10 mg of solubilized vitamin E were used to represent a realistic worst-case scenario. The nonuniform vitamin-E-doped liners and vitamin-E-doped plugs contained similar levels of vitamin E as those in the previous hip simulator study27.
In the first set of experiments, injections of pure vitamin E showed a general inflammatory reaction consistent with a biological response to oil-like substances31-35. Since vitamin E is stabilized in the body by binding to lipoproteins34, a more relevant biological model was intra-articular injections of vitamin E solubilized with Tween 80 and ethanol at a concentration commonly used in drug formulations35,36. No unusual local tissue reaction was seen when the solubilized vitamin E was introduced directly into the joint space. As far as we know, this is the first study investigating the direct effect of intra-articular injection of vitamin E. Subcutaneous plugs showed an inflammatory response associated with the surgical procedure at two weeks, but after twelve weeks both control and vitamin-E-doped ultra-high molecular weight polyethylene plugs showed stable encapsulation with a synovium-like lining and no inflammatory response. This is similar to a previously reported animal study investigating subcutaneously implanted vitamin-E-doped ultra-high molecular weight polyethylene26. These two small-animal studies suggested that the vitamin E eluted from the polyethylene is not likely to cause an inflammatory effect on the surrounding tissue in the joint space.
The canine study in which vitamin-E-doped ultra-high molecular weight polyethylene was used in its intended application of total hip replacement showed no differences in local tissue response and bone ingrowth between control and vitamin-E-doped ultra-high molecular weight polyethylene implants after twelve weeks. Little potential polyethylene wear was observed; thus, any influence of polyethylene wear particles on the local tissue and osseous ingrowth responses was discounted. It is reasonable to assume that some elution occurred from the liners on the basis of the elution seen in the subcutaneous plugs in this study and the elution from unloaded vitamin-E-doped ultra-high molecular weight polyethylene blocks in water (unpublished data). The lack of a qualitative difference in local tissue response between the two vitamin-E-doped liner groups is notable because the nonuniform liners had a higher surface concentration compared with the vitamin-E-doped, radiation cross-linked ultra-high molecular weight polyethylene used clinically. Variations in gross anatomy and histological observations appeared to represent normal variations in the healing response to prosthesis insertion. Such normal variations included a limited range of reactive changes such as a small amount of additional reactive fibrous tissue or fibrin deposition. While the origin of structures in the papillary pseudocapsules is unknown, uniform vitamin-E liners, which would be used clinically, showed a similar frequency of this architecture as the control liners.
This study has several limitations. Larger sample sizes of total hip replacements would be required to provide stronger evidence as to whether the rates of papillary morphology differ between the study groups. Thus, we cannot rule out the possibility that there could be differences in this outcome that were not detected because of the small sample sizes. It is also reasonable to note that a follow-up period of twelve weeks does not represent a long-term biocompatibility study, but bone ingrowth and soft-tissue reactions were not negatively affected during this important initial healing period.
Overall, our findings of similar gross appearance, similar histological appearance, and no significant difference in bone ingrowth between the control and vitamin-E-doped liner groups indicate that the vitamin-E-doped, highly cross-linked polyethylene acetabular components were well tolerated in the canine model. In conclusion, in this study, the presence of vitamin E in highly cross-linked ultra-high molecular weight polyethylene components did not affect the local tissue response or ingrowth of the surrounding bone into the porous implants.