Pierangiola Bracco

Vitamin E-stabilized UHMWPE for Total Joint Implants: A Review

BackgroundOsteolysis due to wear of UHMWPE limits the longevity of joint arthroplasty. Oxidative degradation of UHMWPE gamma-sterilized in air increases its wear while decreasing mechanical strength. Vitamin E stabilization of UHMWPE was proposed to improve oxidation resistance while maintaining wear resistance and fatigue strength.Questions/purposesWe reviewed the preclinical research on the development and testing of vitamin E-stabilized UHMWPE with the following questions in mind: (1) What is the rationale behind protecting irradiated UHMWPE against oxidation by vitamin E? (2) What are the effects of vitamin E on the microstructure, tribologic, and mechanical properties of irradiated UHMWPE? (3) Is vitamin E expected to affect the periprosthetic tissue negatively?MethodsWe performed searches in PubMed, Scopus, and Science Citation Index to review the development of vitamin E-stabilized UHMWPEs and their feasibility as clinical implants.ResultsThe rationale for using vitamin E in UHMWPE was twofold: improving oxidation resistance of irradiated UHMWPEs and fatigue strength of irradiated UHMWPEs with an alternative to postirradiation melting. Vitamin E-stabilized UHMWPE showed oxidation resistance superior to that of irradiated UHMWPEs with detectable residual free radicals. It showed equivalent wear and improved mechanical strength compared to irradiated and melted UHMWPE. The biocompatibility was confirmed by simulating elution, if any, of the antioxidant from implants.ConclusionsVitamin E-stabilized UHMWPE offers a joint arthroplasty technology with good mechanical, wear, and oxidation properties.Clinical RelevanceVitamin E-stabilized, irradiated UHMWPEs were recently introduced clinically. The rationale behind using vitamin E and in vitro tests comparing its performance to older materials are of great interest for improving longevity of joint arthroplasties.

UHMWPE for arthroplasty: past or future?

Wear debris related osteolysis is recognised as being the main cause of failure in joint replacements based on UHMWPE inserts. However, many solutions and “new” polyethylenes have been suggested in order to address this issue. This review discusses “historical” issues associated with UHMWPE, such as oxidation, sterilization method and storage, as well as “new” topics, such as crosslinking and stabilization. The final aim is to aid orthopaedic surgeons in their selection of polyethylene inserts and in the information given to the patients. The main problem for the polymer is degradative oxidation, which is caused by the combination of the irradiation used for sterilization and oxygen, and which leads to a decrease in wear resistance and mechanical properties. Irradiation and packaging in the absence of oxygen can only reduce the oxidation, while sterilization with gas (EtO or gas plasma) is the only method that effectively eliminates it. Manufacturing processes are of great relevance to the clinical duration and must be considered by surgeons. Crosslinked polyethylene has been developed for joint inserts due to its superior wear resistance compared to conventional UHMWPE; to prevent the oxidation, crosslinked polyethylene requires post-irradiation thermal treatment, which reduces its mechanical properties and which depends on the producer. Several good clinical results from the use of crosslinked acetabular cups have reported at mid-term, while early results for knee replacements are also encouraging. Recently, the use of the antioxidant vitamin E (alpha-tocopherol) has been introduced for joint prostheses in order to prevent the oxidation of both crosslinked and noncrosslinked UHMWPE.

Analysis of products diffused into UHMWPE prosthetic components in vivo.

Ten UHMWPE hip inserts, five ethylene oxide and five gamma-ray sterilised in air, were retrieved during surgical revision after aseptic failure. Time in situ varied from 6 to 23 years. First implant was carried out for degenerative arthritis in all cases. The retrieved inserts were cut into two parts perpendicular to the articulate surface and a series of 150 microm thick slices were obtained from the cross-section. These were studied by FTIR microscopy and the absorbed products were extracted with cyclohexane for identification by GC/MS and Py/GC/MS. All retrieved UHMWPE components, independent of the sterilisation method, showed species adsorbed on the surface, which were mainly synovial liquid protein components. In addition, species such as cholesterol, fatty esters of cholesterol and squalene, also originating from synovial liquid, were found in the bulk. The concentration of the different species varies depending on the individual patient.

Oxidation of orthopaedic UHMWPE

Retrieved EtO sterilised acetabular cups usually show much less degradation than gamma-ray sterilised cups. Some of our retrieved EtO sterilised cups did, however, reveal unexpected bulk oxidation. It was observed that this oxidation was always accompanied by whitening of the material. This whitening was found to be due to a break-up of the compression moulded material into its original particles. It was noticed that there was no oxidation in all parts, where the break-up and whitening appeared. The oxidation did, however, occur exclusively in the parts where there was a badly consolidated material. Upon examining shelf aged, unsterilised samples, it was found that the degradation was also present here. This shows that the observed phenomenon is not due to the service in vivo and that it must originate from the processing step. Just as for the retrieved samples, the shelf aged cups only showed oxidation in the bulk and not at the surface. It was concluded that the material used for the cups had been badly fused together during the compression moulding and that the machining had created a bad stress situation in the cups leading to a break-up of the particles. The mechanism that initiates the oxidation is not known, but it is believed that the distribution depends on how the internal stresses have acted to break up the structure. In the areas where the particles have been separated, there is probably a higher availability of oxygen than what is normally observed in UHMWPE.

Char formation in polyvinyl polymers I. Polyvinyl acetate

The study of thermal and thermal-oxidative degradation of polyvinyl acetate is reported. Solid residues of degradation were analysed by FTIR microscopy in the reflection-transmission mode. Aromatization and carbonisation of the solid residues are discussed.

In vitro wear performance of standard, crosslinked, and vitamin-E-blended UHMWPE

Crosslinked vitamin-E-stabilized polyethylene acetabular cups were compared with both commercially available conventional and custom-crosslinked polyethylene acetabular cups in terms of wear behavior, in a hip joint simulator for five millions cycles, using bovine calf serum as lubricant. We correlated the wear experiments results with the chemical characterization of the investigated materials: Fourier transformed infrared (FTIR) spectroscopic analyses, differential scanning calorimetry, and crosslink density measurements were used to assess the chemical characteristics of the pristine materials. In addition, further FTIR analyses and cyclohexane extraction were carried out after the simulator experiments. Lipids absorption was observed in all tested specimens and it has been shown to strongly affect the results of the wear test. Corrected gravimetric wear measurements showed that vitamin-E blended, crosslinked polyethylene wore more than the traditional crosslinked polyethylene but exhibited a much lower wear than conventional ultrahigh-molecular weight polyethylene. The chemical analyses showed that the addition of vitamin E reduced the crosslinking efficiency. Given the correlation between crosslink density and wear resistance, this gave an explanation for the observed wear performances.

Comparison of polypropylene and polyethylene terephthalate (Dacron) meshes for abdominal wall hernia repair: A chemical and morphological study

For the first time, by scanning electron microscopy (SEM), polypropylene (PP) excised meshes (ethylene oxide sterilized) for abdominal wall hernia repair have been shown to be greatly damaged physically, independently of the implantation time, while the polyethylene terephthalate (PET), or Dacron, ones (gamma radiation sterilized), did not undergo alterations due to the sterilization process and were not damaged, even after long implantation periods. Fourier-Transform Infrared Spectroscopy (FTIR) study of PP and PET excised meshes, as well as of their extracts with cyclohexane, has shown the presence of species, such as squalene, palmitic and stearic acid, in some cases, cholesterol, transferred from the surrounding tissues to the polymer during the implantation period. In the case of PP meshes, these small organic molecules would reduce physical and mechanical properties of the material. A hypothesis is presented to account for the better behavior (not in the clinical sense) of PET meshes.

In vitro evaluation of the inflammatory activity of ultra-high molecular weight polyethylene

To understand the inflammatory potential of oxidised ultra high molecular weight polyethylene (ox-UHMWPE) compared with the virgin one (UHMWPE), we analysed in vitro the predisposition of their interaction with plasma proteins and cells involved in the inflammatory response. The adsorption on the surface of the two materials of adhesion proteins (Fibronectin and Albumin), and pro-inflammatory proteins (IgG and IgA) have been studied. Moreover, we have evaluated the materials effect on complement activation and on macrophages and monocytes-neutrophils behaviour. The two UHMWPE chemical forms adsorbed all the proteins studied; the only difference was in complement activation. Enzyme immunoassay results evidenced higher levels of factor Bb and iC3b in plasma after the contact with the oxidised form. Physico-chemical properties of the oxidised UHMWPE affected the attachment of the cells as demonstrated by macrophages adhesion experiments. UHMWPE favoured only a limited peritoneal macrophages (PMs) spreading (round-shaped cells); the cell spreading and presence of microvilli on the cell membranes was evident in the case of the oxidised form, suggesting the activation of these cells on this chemical form. Ox-UHMWPE evidenced a statistically significative increase in chemiluminescence values respect to human unstimulated peripheral blood mononuclear cells, an index of increased cell release of reactive oxygen metabolites. In conclusion, UHMWPE oxidative degradation with its chemical modification induces monocytes-neutrophils chemiluminescence activation and PMs morphology changes correlated with macrophage activation, data consistent with the complement activation results obtained in this study; such modifications, along with changes in mechanical properties, are related to implant failure.

Ultra-High Molecular Weight Polyethylene: Influence of the Chemical, Physical and Mechanical Properties on the Wear Behavior. A Review

Ultra-high molecular weight polyethylene (UHMWPE) is the most common bearing material in total joint arthroplasty due to its unique combination of superior mechanical properties and wear resistance over other polymers. A great deal of research in recent decades has focused on further improving its performances, in order to provide durable implants in young and active patients. From “historical”, gamma-air sterilized polyethylenes, to the so-called first and second generation of highly crosslinked materials, a variety of different formulations have progressively appeared in the market. This paper reviews the structure–properties relationship of these materials, with a particular emphasis on the in vitro and in vivo wear performances, through an analysis of the existing literature.

The induction of MMP-9 release from granulocytes by Vitamin E in UHMWPE

Ultra-high molecular weight polyethylene (UHMWPE) is a biopolymer widely used in orthopaedic implants and its oxidation is considered as major responsible for inflammation and the prosthesis failure. We have studied the effect on the activation of resting human granulocytes of the addition of Vitamin E (Vit.E, alpha-tocopherol), a natural biological antioxidant and antiinflammatory agent, to UHMWPE. We have measured changes in granulocytes morphology and respiratory burst by flow cytometry using Dihydrorhodamine 123 and matrix metalloproteinase 9 (MMP-9, gelatinase B) release and activity in the growth medium using substrate zymography following contact (60 min at 37 degrees C) with cell grade polystyrene (PS), normal UHMWPE (PE) and Vit.E added UHMWPE (PE Vit.E). FTIR analyses showed that the surfaces of PE and PE-Vit.E were not significantly different. PS, PE and PE Vit.E did not alter granulocytes morphology and respiratory burst as showed by the mean fluorescence emitted (PS=12.0+/-0.1, PE=13.0+/-0.4, PE Vit.E=14.5+/-0.1). PE Vit.E was able to increase MMP-9 release compared to PS and normal PE (215+/-16% of the control, p<0.001). The PE Vit.E-induced MMP-9 release was abolished by okadaic acid (0.5 nM), suggesting a direct role of Vit.E in the phenomenon.