Mechanical Properties and Porosity of Acrylic Cement Bone Loaded with Alendronate Powder.

Aseptic loosening is the most common complication of joint replacement. Previous studies showed that acrylic bone cement loaded with a commercially-available alendronate powder (APAC) had good promise against wear debris-mediated osteolysis for prevention of aseptic loosening. The purpose of the present study was to investigate the effect of adding alendronate powder to an acrylic bone cement on quasi-static mechanical properties (namely, compressive strength, compressive modulus, tensile strength, and flexural strength), fatigue life, porosity, and microstructure of the cement. The results showed that adding up to 1 wt./wt.% alendronate powder exerted no detrimental effect on any of the quasi-static mechanical properties. However, the fatigue life of APAC decreased by between ~17% and ~27 % and its porosity increased by between ~ 5-7 times compared with corresponding values for the control cement (no alendronate powder added). Fatigue life was negatively and significantly correlated with porosity. Considering that fatigue life of the cement plays a significant role in joint replacement survival, clinical use of APAC cannot be recommended.

Effect of Low-Frequency Pulsed Ultrasound on Drug Delivery, Antibacterial Efficacy, and Bone Cement Degradation in Vancomycin-Loaded Calcium Phosphate Cement.

BACKGROUND Calcium phosphate cement (CPC) has been applied as a biodegradable antibiotic carrier in osteomyelitis. However, the drug delivery, antibacterial efficacy, and degradation rate of CPC are insufficient and require further improvement in clinical application. MATERIAL AND METHODS Vancomycin-loaded CPC columns were prepared, and eluted in simulated body fluid. The drug delivery was assessed in the ultrasound group and control group by fluorescence polarization immunoassay. The antibacterial efficacy of vancomycin in the ultrasound group and control groups was investigated by standard plate count method. Low-frequency pulsed ultrasound (46.5 kHz, 900 mW/cm²) was used to produce a sinusoidal wave in the ultrasound groups. The percentage of residual weight was evaluated to assess the degradation of CPC. RESULTS The concentration and cumulatively released percentage of vancomycin in the ultrasound group were higher than that in the control group at each time point (p<0.05). The duration of vancomycin concentration over the level of minimum inhibitory concentration was significantly prolonged in the ultrasound group (p<0.05). Antibacterial efficacy of vancomycin in the ultrasound group was significantly greater than that in the control group with same concentration of vancomycin (p<0.05). The percentage of residual weight in the ultrasound group was significantly less than that in the control group (p<0.05). CONCLUSIONS Low-frequency pulsed ultrasound can enhance vancomycin release, prolong the duration of vancomycin concentration at high levels, and accelerate the degradation rate of vancomycin-loaded CPC.

Cementless Porous Tantalum Monoblock Tibia vs Cemented Modular Tibia in Primary Total Knee Arthroplasty: A Meta-Analysis.

BACKGROUND: With the introduction of new fixation systems and designs, there has been a recent reemergence of interest in cementless fixation of the tibial component in total knee arthroplasty. However, little is known regarding the clinical features and survivorship of the cementless porous tantalum monoblock tibial component compared to the conventional cemented modular tibial component. METHODS: We conducted a literature search of multiple databases for comparative studies published before June 2015 that investigated the outcomes of cementless porous tantalum monoblock tibia vs conventional cemented modular tibia. A pooled analysis was performed. The outcomes of interest were postoperative functional score, range of motion, Western Ontario and McMaster University Osteoarthritis Index, total complications, reoperation, radiolucent lines, loosening of the tibial component, and length of operation. RESULTS: Six studies involving 977 patients were eligible for the meta-analysis. The use of a cementless porous tantalum monoblock tibial component may associate with a slightly higher functional score, fewer radiolucent lines, and shorter operation. No significant difference was seen in regard to the range of motion, Western Ontario and McMaster University Osteoarthritis Index, total complications, reoperation, and loosening of the component between the 2 groups. CONCLUSION: However, due to variation among the included studies, the use of cementless porous tantalum monoblock tibia seems to achieve no substantial superiority over that of the conventional cemented modular tibia at 5-year follow-up. Data concerning the long-term prognosis of this novel implant should continue to be collected and analyzed.

In vitro and in vivo evaluation of antibacterial activity of polyhexamethylene guanidine (PHMG)-loaded TiO2 nanotubes.

Artificial joint replacement is an effective surgical method for treating end-stage degenerative joint diseases, but peripheral bacterial infection of prosthesis can compromise the effect of the surgery. Herein, antibacterial effects of titanium dioxide nanotubes (TNTs) coated with polyhexamethylene guanidine (PHMG) were examined via in vitro and in vivo experiments. TNTs with a pore diameter 46.4 ± 5.9 nm and length of 300-500 nm for the slice and 650-800 nm for the rod were fabricated by anodization. Then, 3.46 ± 0.40 mg and 1.27 ± 0.28 mg of PHMG were coated onto the TNT slice and rod, respectively. In vitro studies of the release of PHMG showed that the antibacterial agent was released in two stages: initial burst release and relatively slow release. In vitro and in vivo antibacterial studies showed that the PHMG-loaded TNTs (PHMG-TNTs) had excellent antibacterial abilities to prevent bacterial infections. Clinical pathological analysis of rabbit femurs indicated that the implanted PHMG-TNTs had no apparent pathological changes. Real-time quantitative reverse transcription polymerase chain reaction analysis of the femur tissues around the implants showed that the expression of osteogenic-related genes, including runt-related transcription factor 2, osteocalcin, alkaline phosphatase, bone sialoprotein, bone morphogenetic protein 2 and vascular endothelial growth factor A, was significantly upregulated in the PHMG-TNT implanted group as compared to the other groups. Overall, these findings provide a promising approach for the fabrication of antibacterial and bone biocompatible titanium-based implants in orthopedics.

[Biomechanical strength of bone cement impregnated with diphosphonate].

OBJECTIVE: To investigate the biomechanical strength of diphosphonate impregnated bone cement (DIBC). METHODS: DIBC specimens were manufactured and randomly assigned to the control groups and the DIBC groups. According to the corresponding ASTM/ISO standards, the static biomechanical strength and the fatigue limit were tested systematically. The particle size distribution of diphosphonate powder was analyzed with the laser light scattering method. The fatigue test results, given as number of cycles-to-failure, were analyzed using the linearized format of the two-parameter Weibull function. RESULTS: With the drug load increased, there was a slight increase in static biomechanical strength and a moderate decrease in fatigue limit, both with statistical significance. When immersed in PBS before the tests, the DIBC specimens presented an overall significant decrease of static biomechanical strength and fatigue limit. The profile of drug particle sizes presented a normal distribution. CONCLUSIONS: The adopted diphosphonate is a much homogeneous powder which contains particles with a low range of sizes. The impregnation of diphosphonate exerted no or less negative effect on the biomechanical strength of the acrylic bone cement, of which the static strength of DIBC is maintained high above the ASTM/ISO standards.

Low-intensity pulsed ultrasound enhances antibiotic release of gentamicin-loaded, self-setting calcium phosphate cement.

Objective This study aimed to investigate the effect of low-intensity pulsed ultrasound on antibiotic release from gentamicin-loaded, self-setting calcium phosphate cement. Methods A gentamicin-loaded calcium phosphate cement cylinder was eluted in stimulated body fluid. Low-intensity pulsed ultrasound (46.5 kHz, 200 mW/cm2) was used to produce a sinusoidal wave in the experimental group. Non-gentamicin calcium phosphate cement was used in the control group. Results The transient concentration and cumulatively released percentage of gentamicin in the ultrasound group were higher than those in control group at every time point. The duration of gentamicin concentrations over the level of the minimum inhibitory concentration was significantly prolonged in the ultrasound group compared with the control group. Antibacterial efficacy of gentamicin in the ultrasound group was significantly better than that in the control group with the same concentration of gentamicin. Conclusion Low-intensity pulsed ultrasound enhances antibiotic release, providing sustained antibiotic release at high concentrations. This increases the antibacterial effect of gentamicin.

Comparison of tourniquet application only during cementation and long-duration tourniquet application in total knee arthroplasty: a meta-analysis.

BACKGROUND: Tourniquet is widely used by orthopedic surgeons in total knee arthroplasty (TKA). However, there are still controversies on the optimal timing of tourniquet application. The aim of this meta-analysis was to compare the effect and safety of tourniquet application only during cementation with long-duration tourniquet application in TKA. METHODS: An electronic literature search of PubMed, the Cochrane library, Embase, and Web of Science was conducted in July 2017. All randomized controlled trials (RCTs) comparing tourniquet application only during cementation with long-duration tourniquet application in TKA were included. RevMan 5.3 software was selected to perform the meta-analysis. RESULTS: Seven studies involving 440 TKAs were included for meta-analysis. The results suggested that although significant less intraoperative and total blood loss were observed with long-duration tourniquet application, tourniquet application only during cementation would not increase the number of transfusion and operation time. Tourniquet application only during cementation results in less knee pain on post-operative day 1 (POD 1), less time needed to achieve straight-leg raise, and less minor complications following TKA. CONCLUSIONS: Tourniquet application only during cementation might reduce the rate of minor complications and have faster functional recovery during the early rehabilitation period following TKA, but it could not limit intraoperative and total blood loss. No definitive conclusions can be drawn based on the current evidences. Further, large well-designed RCTs with extensive follow-up are still needed to validate this research.

Osteochondral repair using the combination of fibroblast growth factor and amorphous calcium phosphate/poly(L-lactic acid) hybrid materials.

A novel amorphous calcium phosphate (ACP)/poly(L-lactic acid) (PLLA) material, which can experience morphological variations in the microstructure is supposed to be a suitable candidate as scaffold for cartilage tissue-engineering. The purpose of this study was to evaluate the efficacy of this scaffold combined with basic fibroblast growth factor (bFGF) to repair articular cartilage defects in a rabbit model. Forty-two osteochondral defects created in the femoral condyles were (a) left untreated, (b) treated by PLLA combined with bFGF, or (c) ACP/PLLA loaded with bFGF. The treatment of PLLA incorporated with bFGF improved defect filling compared with that left untreated, while the regenerated tissue was mainly fibrocartilage and showed little bone formation with only a small amount of collagen type II (Col II) and no aggrecan gene message measured. When implanted with ACP/PLLA and bFGF, most of the defects were filled with a well-established layer of cartilage tissue with abundance of cartilaginous extracellular matrix accumulation observed. Positive immunohistochemical staining of Col II was observed. High levels of Col II and aggrecan message were also detected by RT-PCR. These results indicate the feasibility of using the combination of ACP/PLLA with bFGF for cartilage repair.

Continuous wave ultrasound enhances vancomycin release and antimicrobial efficacy of antibiotic-loaded acrylic bone cement in vitro and in vivo.

Although antibiotic-loaded bone cement (ALBC) is used as a drug delivery vehicle to decrease infection rates, the varied clinical effect of the antibiotic release remains controversial. The objective of this study is to investigate the enhancement of continuous wave ultrasound (CWU) on vancomycin release and antimicrobial efficacy of ALBC in vitro and in vivo. We measured vancomycin concentrations after a 0.5-h exposure of CWU. The results showed that CWU increased the drug elution by 2.57-27.44% when compared with the controls in vitro. Ultrasonic intensity and vancomycin load both had a significant effect on the cumulative drug elution at 10.5 h, with a significant interaction between each other. We also implanted ALBC specimens into hip joints of sixteen New Zealand White female rabbits after inoculations of Staphylococcus aureus around primary implants for 30 days. Vancomycin concentrations in the hip cavity and urinary elimination of vancomycin were both measured after intermittent exposures of CWU. The results showed that CWU increased local Tmax by 47.6 microg/mL and urinary elimination of vancomycin by 109.56 microg, but failed to prolong local T>MIC. On day 30 after the implantation, assessment in clinical performance, radiology, bacteriology, and histology all showed a tendency of decreased bacterial vitality and relieved inflammation in the infected hip treated by CWU. This study suggested that CWU could effectively enhance vancomycin release and antimicrobial efficacy of ALBC, which may be of clinical significance for treating prosthesis-related infections.

Low-intensity pulsed ultrasound (LIPUS) prevents periprosthetic inflammatory loosening through FBXL2-TRAF6 ubiquitination pathway.

Previous studies have shown that Low intensity pulsed ultrasound(LIPUS) prevents polyethylene-debris-induced periprosthetic loosening in vivo, but the details of the mechanism by which it does so remain unclear. In this article, we used polyethylene debris induced RAW 264.7 cells as the in vitro model, and tested the effect of LIPUS on this model. Changes in the level of inflammatory cytokines, cell proliferation, and apoptosis were assessed. Gene overexpression and siRNA technique were applied, and the levels of expression of FBXL2, TRAF6, ERK, and related inflammatory cytokines were also measured. Results indicated that FBXL2-mediated TRAF6 ubiquitination and degradation also plays an important role in aseptic periprosthetic loosening process, and LIPUS prevents such loosening by strengthening this pathway.

Three-dimensional printing akermanite porous scaffolds for load-bearing bone defect repair: An investigation of osteogenic capability and mechanical evolution.

Some Ca-Mg-silicate ceramics have been widely investigated to be highly bioactive and biodegradable, whereas their osteogenic potential and especially biomechanical response in the early stage in vivo are scarcely demonstrated. Herein, the osteogenesis capacity and mechanical evolution of the akermanite (Ca2MgSi2O7) porous materials manufactured by ceramic ink writing three-dimensional printing technique were investigated systematically in a critical size femur defect model, in comparison with the clinically available ß-tricalcium phosphate porous bioceramic. Such three-dimensional printed akermanite scaffolds possess fully interconnected pores of ∼280 × 280 µm in size and over 50% porosity with appreciable compressive strength (∼71 MPa), that is 7-fold higher than that of the ß-tricalcium phosphate porous bioceramics (∼10 MPa). After 6 weeks and 12 weeks of implantation, the percentage of newly formed bone and more new bone was observed in the akermanite group as compared with the ß-tricalcium phosphate group (p < 0.01). Moreover, significant higher mRNA expressions of osteogenic genes were detected in the akermanite group by PCR analysis (p < 0.01). The in vivo mechanical strength decreased during the process of implantation, but maintained a relative high level (∼14 MPa) which was still higher than that of the host cancellous bone (5-10 MPa) at 12 weeks post-implantation. On the contrary, the ß-tricalcium phosphate scaffold always exhibited a very low mechanical strength (∼8 MPa). These results suggest that the three-dimensional printed akermanite scaffolds are promising for the bone tissue regeneration and repair of load-bearing bone defects.

3D Printing Surgical Implants at the clinic: A Experimental Study on Anterior Cruciate Ligament Reconstruction.

Desktop three-dimensional (3D) printers (D3DPs) have become a popular tool for fabricating personalized consumer products, favored for low cost, easy operation, and other advantageous qualities. This study focused on the potential for using D3DPs to successfully, rapidly, and economically print customized implants at medical clinics. An experiment was conducted on a D3DP-printed anterior cruciate ligament surgical implant using a rabbit model. A well-defined, orthogonal, porous PLA screw-like scaffold was printed, then coated with hydroxyapatite (HA) to improve its osteoconductivity. As an internal fixation as well as an ideal cell delivery system, the osteogenic scaffold loaded with mesenchymal stem cells (MSCs) were evaluated through both in vitro and in vivo tests to observe bone-ligament healing via cell therapy. The MSCs suspended in Pluronic F-127 hydrogel on PLA/HA screw-like scaffold showed the highest cell proliferation and osteogenesis in vitro. In vivo assessment of rabbit anterior cruciate ligament models for 4 and 12 weeks showed that the PLA/HA screw-like scaffold loaded with MSCs suspended in Pluronic F-127 hydrogel exhibited significant bone ingrowth and bone-graft interface formation within the bone tunnel. Overall, the results of this study demonstrate that fabricating surgical implants at the clinic (fab@clinic) with D3DPs can be feasible, effective, and economical.

In vitro and in vivo evaluation of vancomycin-loaded PMMA cement in combination with ultrasound and microbubbles-mediated ultrasound.

Ultrasound (US) has been used to increase elution of antibiotic from an antibiotic-loaded poly(methyl methacrylate) (PMMA) bone cement (ALBC). We aimed to further investigate whether microbubbles-mediated US (US + MB) facilitate elution of vancomycin (VAN) from cylindrical specimens and enhance the activity of the eluted antibiotic against Staphylococcus aureus (S. aureus) in vitro. The study groups comprised cylindrical bone cement fabricated with VAN (VAN), ALBC using US (VAN + US), and ALBC using MB-mediated US (VAN + US + MB). We also carried out an in vivo study involving the activity of VAN from cylindrical cement implanted in tibiae of New Zealand white rabbits inoculated with S. aureus. We found that (1) in vitro, elution from VAN + US + MB cylinders was significantly higher than from either the VAN or VAN + US specimens; (2) the activity of the eluted VAN from the VAN + US + MB cylinders against planktonic S. aureus was significantly higher than from either the control or VAN or VAN + US specimens; and (3) in the rabbits, the activity of the eluted VAN from the VAN + US + MB cylinders against S. aureus was significantly higher than from either the control or VAN or VAN + US specimens. The present results suggest that VAN-loaded PMMA cement irradiated with MB-mediated US may have a role in controlling prosthetic joint infection.

Total hip arthroplasty with cementless cups and femoral head autografts for patients with hip dysplasia and osteoarthritis.

OBJECTIVE: To evaluate the outcome of total hip arthroplasty (THA) with cementless cups and femoral head autografts for patients with hip dysplasia and osteoarthritis. METHODS: Between 1995 and 2002, we implanted 23 cementless cups and femoral head autografts in 20 patients with hip dysplasia and osteoarthritis. In this study, a retrospective study was made on 21 hips in 20 patients (18 females and 2 males, aged 50 years on an average) with developmental hip dysplasia treated by THA with a cementless cup and femoral head autograft. The acetabular cup was placed at the level of the true acetabulum and all the patients required autogenous femoral head grafts due to acetabular deficiency. The average rate of the acetabular cup covered by the femoral head autograft was 31% (ranging from 10% to 45%). Eight hips had less than 25% cup coverage and thirteen between 25% and 50%. The average follow-up period was 4.7 years (range, 1-8 years). The replacing outcome was evaluated by modified Harris hip score. Preoperative and follow-up radiographs were made. RESULTS: All the autografts were united to the host bones. No autograft was collapsed or no component from the hip was loosed in all the patients. According to the modified Harris hip score, the average hip score increased from 46 before operation to 89 at the final review. Before operation, the leg-length discrepancy was greater than 2 cm in all the patients except one with bilateral hip dysplasia. After operation, only 2 out of 20 patients had a leg-length discrepancy greater than 1 cm. Three hips showed minor bone resorption in the lateral portion of the graft, which did not support the cup. Three hips developed Grade 1 Brooker heterotopic ossification and one developed Grade 2. CONCLUSIONS: THA with a cementless cup and a femoral head autograft for patients with osteoarthritis resulted from hip dysplasia can result in favorable outcomes. This method can provide reliable acetabular fixation and restore the acetabular bone stock in patients with developmental hip dysplasia when the cementless cup covered by the graft does not exceed 50%.

[Total hip arthroplasty with uncemented cup and femoral head autografts for coxarthrosis due to dysplasia].

OBJECTIVE: To evaluate the outcomes of total hip arthroplasty (THA) for coxarthrosis due to dysplasia with acetabular reconstruction of an uncemented cup in conjunction with a femoral head autograft. METHODS: A retrospective study was made on 21 hips in 20 patients (18 female and 2 male; average age, 50 years) with developmental hip dysplasia treated by THA with use of an uncemented cup. The acetabular cup was placed at the level of the true acetabulum; all patients required autogenous femoral head grafts due to acetabular deficiency. The average coverage of the acetabular cup by the femoral head autograft was 31% (range, 10% to 45%). Eight hips had less than 25% cup coverage and 13 between 25% and 50%. The average follow-up period was 4.7 years (range, 1-8 years). All patients were evaluated with the use of a modified Harris hip score. Radiographic evaluations were made by preoperative and follow-up. RESULTS: All autografts were seen to be united to host-bone. No collapse of the autograft and no hip had the evidence of loosening of component seen in all patients. According to the modified Harris hip score, the average hip score increased from 46 at preoperation to 89 at the final review. Preoperative leg-length discrepancy was greater than 2 cm seen in all except 1 patient with bilateral hip dysplasia. After surgery, only 2 of 20 patients still had a leg-length discrepancy greater than 1 cm. Three hips showed minor resorption in the lateral portion of the graft which was not supporting the cup. Three hips developed grade 1 Brooker heterotopic ossification and one had grade 2. CONCLUSIONS: THA with an uncemented cup in conjunction with a femoral head autograft for coxarthrosis due to dysplasia could obtain favorable results. This method could provide reliable acetabular fixation and appeared to restore acetabular bone stock in patients with developmental hip dysplasia when the coverage of the cementless cup by the graft does not exceed 50%.

Effects of cartilage oligomeric matrix protein on bone morphogenetic protein-2-induced differentiation of mesenchymal stem cells.

OBJECTIVE: To investigate the effect of overexpression of cartilage oligomeric matrix protein (COMP) on bone morphogenetic protein-2 (BMP-2) induced osteogenic and chondrogenic differentiation of mesenchymal stem cells (MSCs). In this study, we used liposomes to transfect MSCs with plasmid encoding COMP and then induced the transfected MSCs to differentiate in osteogenic and chondrogenic differentiation media containing BMP-2. METHODS: MSCs transfected with plasmid DNA encoding recombinant human COMP were induced to differentiate into osteocytes and chondrocytes by BMP-2. Real-time polymerase chain reaction (PCR) assays of osteogenesis-related markers (collagen type I alpha 1, runt-related transcription factor 2, osteopontin, bone gla protein) and chondrogenesis-related markers (collagen type II alpha 1, sry-related high-mobility group box 9, Aggrecan) was performed to evaluate the process of cell differentiation. Cell differentiation was evaluated by alkaline phosphatase (ALP) and Alizarin red S stains for osteogenic differentiation and alcian blue staining for chondrogenic differentiation. RESULTS: Real-time PCR assay showed significantly greater COMP expression by MSCs when COMP gene had been transfected into the cells (P < 0.01). Overexpression of COMP down-regulated expression of osteogenesis-related markers and up-regulated expression of chondrogenesis-related markers. ALP staining and Alizarin red S staining were weakened, whereas alcian blue staining was enhanced. CONCLUSION: Overexpression of COMP inhibits BMP-2-induced osteogenic differentiation and promotes BMP-2-induced chondrogenic differentiation. These findings may provide new insights for cartilage tissue engineering. The experiments in the present study were all in vitro, which has potential limitations. Further in vivo studies to investigate the effects of COMP in animal models are necessary, which will be the next step in our research.

Engineering scaffolds integrated with calcium sulfate and oyster shell for enhanced bone tissue regeneration.

Engineering scaffolds combinging natural biomineral and artificially synthesized material hold promising potential for bone tissue regeneration. In this study, novel bioactive calcium sulfate/oyster shell (CS/OS) composites were prepared. Comparing to CS scaffold, the CS/OS composites with a controllable degradation rate displayed enhanced mineral nodule formation, higher alkaline phosphate (ALP) activity and increased proliferation rate while treated osteocytes. In CS/OS composites group, elevated mRNA levels of key osteogenic genes including bone morphogenetic protein-2 (BMP-2), runt-related transcription factor 2 (Runx2), osterix (Osx), and osteocalcin (OCN) were observed. Furthermore, The up-regulation of BMP-2 and type I collagen (COL-I) was observed for CS/OS composites relative to a CS group. Scaffolds were implanted into critical-sized femur cavity defects in rabbits to investigate the osteogenic capacity of the composites in vivo. The CS/OS scaffolds with proper suitable times and mechanical strength strongly promoted osteogenic tissue regeneration relative to the regeneration capacity of CS scaffolds, as indicated by the results of histological staining. These results suggest that the OS-modified CS engineering scaffolds with improved mechanical properties and bioactivity would facilitate the development of a new strategy for clinic bone defect regeneration.

Low-intensity pulsed ultrasound (LIPUS) may prevent polyethylene induced periprosthetic osteolysis in vivo.

We investigated the effect of local low-intensity pulsed ultrasound (LIPUS) on polyethylene debris induced periprosthetic osteolysis. The periprosthetic osteolysis model was made by injecting endotoxin-free pure polyethylene particles into the distal part of the femur canal and inserting a stainless steel plug into this femur. The effects of polyethylene and LIPUS were assessed histologically and by the shear strength test and periprosthetic bone mineral density (BMD) test. Sixteen rabbits received a stainless steel plug on one side and both polyethylene and a stainless steel plug on the other side. Three months later, the side that received polyethylene showed periprosthetic osteolysis. Subsequently, another 16 rabbits received polyethylene plus local LIPUS (200 mW/cm(2) for 20 min daily) on one side and polyethylene alone on the other side. Three months later, LIPUS effectively prevented the periprosthetic osteolysis caused by polyethylene in this rabbit model.