PURPOSE OF STUDY: Total joint replacements (TJR) have become the cornerstone of modern orthopedic surgery. A great majority of TJR employs ultrahigh molecular weight polyethylene (UHMWPE) liners. TJR manufacturers use many different types of UHMWPE, which are modified by various combinations of crosslinking, thermal treatment, sterilization and/or addition of biocompatible stabilizers. The UHMWPE modifications are expected to improve the polymer's resistance to oxidative degradation and wear (release of microparticles from the polymer surface). This manuscript provides an objective, non-commercial comparison of current UHMWPE formulations currently employed in total knee replacements. MATERIALS AND METHODS: UHMWPE liners from 21 total knee replacements (TKR) were collected which represent the most implanted liners in the Czech Republic in the period 2020-2021. The UHMWPEs were characterized using several methods: infrared microspectroscopy (IR), non-instrumented and instrumented microindentation hardness testing (MH and MHI), differential scanning calorimetry (DSC), thermogravimetric analysis (TGA), and solubility measurements. The above-listed methods yielded quite complete information about the structure and properties of each UHMWPE type, including its potential long-term oxidation resistance. RESULTS: For each UHMWPE liner, IR yielded information about immediate oxidative degradation (in the form of oxidation index, OI), level of crosslinking (trans-vinylene index, VI) and crystallinity (CI). The MH and MHI testing gave information about the impact of structure changes on mechanical properties. The remaining methods (DSC, TGA, and solubility measurements) provided additional information regarding the structure changes and resistance to long-term oxidative degradation. Statistical evaluation showed significant differences among the samples as well as interesting correlations among the UHMWPE modifications, structural changes, and mechanical performance. DISCUSSION: Surprisingly enough, UHMWPE materials from different manufacturers showed quite different properties, including the resistance against the long-term oxidative degradation, which is regarded as one of the main reasons of TJR failures. The most promising UHMWPE types were crosslinked materials with biocompatible stabilizers. CONCLUSIONS: Current UHMWPE liners from different manufactures used in total knee replacements exhibit significantly different structure and properties. From the point of view of clinical practice, the traditional UHMWPE types, which contained residual radicals from irradiation and/or gamma sterilization, showed inferior resistance to oxidative degradation and should be avoided. The best properties were observed in modern UHMWPE types, which combined crosslinking, biocompatible stabilizers, and sterilization by ethylenoxide or gas plasma. KEY WORDS: UHMWPE; knee replacements; oxidative degradation; infrared spectroscopy; microhardness.

• MeSH
• Biocompatible Materials chemistry   MeSH
• Calorimetry, Differential Scanning MeSH
• Humans MeSH
• Polyethylenes * chemistry   MeSH
• Prosthesis Design MeSH
• Knee Prosthesis * MeSH
• Thermogravimetry MeSH
• Materials Testing * methods   MeSH
• Arthroplasty, Replacement, Knee * instrumentation   methods   MeSH
• Check Tag
• Humans MeSH
• Publication type
• English Abstract MeSH
• Journal Article MeSH
• Comparative Study MeSH

PURPOSE OF THE STUDY In clinical practice UHMWPE is the most commonly used material for manufacturing articular components of joint replacements. The purpose of this study is to find out whether repeated ethylene oxide sterilization results in oxidative degradation of UHMWPE or not and also whether the oxidative degradation of various types of ethylene oxide-sterilized UHMWPE depends on storage time or not. MATERIAL AND METHODS The set included 12 samples of UHMWPE (three samples with different modifications (virgin PE, with E vitamin and cross-linked with thermal treatment) and different number of sterilizations (0×-3×)). The set also included 8 samples of commercial components of hip or knee replacements sterilized with ethylene oxide and stored for different storage periods. The oxidative degradation was assessed by infrared microspectroscopy, based on which the oxidation index (OI), transvinylene index (VI), crystallinity index (CI) and E vitamin index (EI) were calculated. Mechanical properties of UHMWPE were obtained through microhardness measurements. Statistical processing of the results was performed. RESULTS In all the samples, very low oxidative degradation values were reported (most OI values < 0.1). All radiation crosslinked UHMWPE samples showed an increased VI index and a slightly lower crystallinity index. All unmodified samples (irrespective of whether or not and how many times or how long ago the samples were sterilized with EtO) had almost zero value of VI. Changes in crystallinity were negligible (in the rage of 0.56-0.63), which required very accurate measurements of micromechanical properties. Yet, linear correlation was established between microhardness and crystallinity. DISCUSSION All the mentioned indices changed as anticipated: OIs were very low and slightly increased with time of storage, VIs of radiation crosslinked samples grew in proportion to the total gama radiation dose, CIs decreased in samples thermally treated by remelting, and EIs were very low due to negligible concentration of stabiliser (0.1%) in the samples of medical grade UHMWPE. CONCLUSIONS All samples showed zero or minimum oxidative degradation. This confirmed that neither ethylene oxide sterilization, nor multiple EtO sterilization or longer storage of polymer after ethylene oxide sterilization result in major oxidative degradation. Key words: UHMWPE, ethylene oxide, sterilization, oxidation, infrared spectroscopy, microhardness.

• MeSH
• Arthroplasty, Replacement * MeSH
• Ethylene Oxide * MeSH
• Humans MeSH
• Polyethylenes MeSH
• Sterilization methods   MeSH
• Vitamins MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH

• MeSH
• Anti-Infective Agents MeSH
• Microbiological Phenomena MeSH
• Sterilization MeSH

• Conspectus
• Veřejné zdraví a hygiena
• NML Fields
• hygiena
• NML Publication type
• kolektivní monografie

Bone defect is a noteworthy health problem and is the second most transplanted tissue after blood. Numerous bone grafts are designed and applied in clinics. Limitations, however, from different aspects still exist, including limited supply, mechanical strength, and bioactivity. In this study, two biomimetic peptides (P2 and P6) are incorporated into a composite bioactive xeno hybrid bone graft named SmartBonePep®, with the aim to increase the bioactivity of the bone graft. The results, which include cytotoxicity, proliferation rate, confocal microscopy, gene expression, and protein qualification, successfully prove that the SmartBonePep® has multi-modal biological effects on human mesenchymal stem cells from bone marrow. The effective physical entrapment of P6 into a composite xeno-hybrid bone graft, withstanding manufacturing processes including exposure to strong organic solvents and ethylene oxide sterilization, increases the osteogenic potential of the stem cells as well as cell attachment and proliferation. P2 and P6 both show a strong biological potential and may be future candidates for enhancing the clinical performance of bone grafts.

• Publication type
• Journal Article MeSH

Ethylene oxide (EO), a carcinogenic chemical used as an industrial intermediate and sterilant, forms covalent adducts with DNA and proteins. The adduct with N-terminal valine [N-(2-hydroxyethyl)-l-valine, HEV] in blood protein globin has been employed as a principal biomarker of cumulative exposures to EO. However, as sampling of blood is inconvenient in routine occupational health practice, a non-invasive alternative to globin analysis has been investigated. Following identification of N-(2-hydroxyethyl)-l-valyl-l-leucine (HEVL) as ultimate cleavage product of EO-adducted globin excreted in the rat urine, here we report for the first time on the presence of HEVL in the urine of humans. In 18 sterilization workers, urinary HEVL ranged from 0.67 to 11.98 μg/g creatinine (mean ± SD: 5.04 ± 3.14 μg/g creat) and correlated with HEV: HEVL (μg/g creat) = 0.833 HEV (nmol/g globin) + 1.19 (R2 = 0.45). As unexpectedly high levels of urinary HEVL were found also in controls (mean ± SD: 0.97 ± 0.37 μg/g creat, n = 32), HEVL is not proposed for the accurate assessment of sub-ppm exposures to EO. On the other hand, non-invasive sampling and facile work-up procedure predetermine HEVL for screening purposes to identify subjects approaching to or exceeding occupational exposure limit for EO (1.8 mg/m3) to be re-examined by the more sensitive reference analysis for HEV.

• MeSH
• Biomarkers urine   MeSH
• Biological Monitoring methods   MeSH
• Adult MeSH
• Ethylene Oxide urine   MeSH
• Carcinogens toxicity   MeSH
• Middle Aged MeSH
• Humans MeSH
• Occupational Exposure adverse effects   MeSH
• Valine urine   MeSH
• Check Tag
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Male MeSH
• Female MeSH
• Publication type
• Journal Article MeSH

PURPOSE OF THE STUDY For an orthopedic surgeon it is difficult or even impossible to estimate the real quality of ultrahigh molecular weight polyethylene (UHMWPE) liners that are used in the total joint replacements (TJR) just on the basis of information given by the manufacturers. At the same time, the quality of the UHMWPE liner can impact strongly on the total lifespan of the implanted TJR. This work aims at independent, objective comparison of properties of the UHMWPE liners for total hip replacements (THR), which are most frequently used in the Czech Republic. MATERIAL AND METHODS We analyzed seventeen most frequently implanted UHMWPE cups of different manufacturers implanted in the Czech Republic between 2014 and 2015 and four control samples prepared by standard industrial-scale procedures according to our instructions, whose modification (crosslinking, thermal treatment, stabilization and sterilization) was known in detail. The UHMWPE polymer was characterized by four independent microscale methods, suitable for relatively small and irregular specimens such as THR cups: infrared microspectroscopy (IR), differential scanning calorimetry (DSC), and thermogravimetric analysis (TGA). RESULTS The employed methods yielded quite complete information about the investigated UHMWPE materials. IR spectra enabled us to calculate oxidation indexes (OI, measure of oxidative damage), trans-vinylene indexes (VI, measure of absorbed radiation dose during crosslinking and/or sterilization) and crystallinity indexes (CI, amount of crystalline phase that strongly influences mechanical performance). DSC curves were employed in calculation of crystallinities (wc, proportional to CI) and melting points (Tm, proportional to the average thickness of crystalline lamellae). MH measurements confirmed that the observed structure changes showed a real impact on mechanical properties. TGA experiments gave rough estimate of stabilization and, consequently, possible long-term oxidation resistance. Significant correlations among oxidative damage (OI), crystallinity (CI, wc) and microhardness (Hv) were statistically proven. The highest oxidative degradation was usually observed in samples thermally treated by annealing and/or sterilized by gamma irradiation. DISCUSSION The results confirmed our expectations that the UHMWPE liners from various manufacturers can be significantly different as far as their molecular structure, supermolecular structure, and mechanical properties are concerned. The differences among the various UHMWPE can be expected to increase after the implantation during in vivo. CONCLUSIONS From the clinical practice point of view, the results showed the following facts: (i) In the field of THR, all manufactures prefer crosslinked types of UHMWPE due to their increased wear resistance; non-crosslinked UHMWPEs are regarded as obsolete. (ii) Most of the manufacturers prefer ethylene oxide or gas plasma sterilization to gamma sterilization because the gammasterilized UHMWPEs exhibit lower long-term oxidation resistance. (iii) Modern trend is the stabilization of UHMWPEs with vitamin E. Key words: UHMWPE, hip replacements, oxidative degradation, infrared spectroscopy, microhardness.

• MeSH
• Humans MeSH
• Arthroplasty, Replacement, Hip * MeSH
• Polyethylenes * MeSH
• Materials Testing MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH
• Geographicals
• Czech Republic MeSH

Ethylene oxide (EO), a genotoxic industrial chemical and sterilant, forms covalent adducts with DNA and also with nucleophilic amino acids in proteins. The adduct with N-terminal valine in globin [N-(2-hydroxyethyl)valine (HEV)] has been used in biomonitoring of cumulative exposures to EO. Here we studied in rats the fate of EO-adducted N-termini of globin after life termination of the erythrocytes. Rat erythrocytes were incubated with EO to produce the HEV levels in globin at 0.4-13.2 µmol/g as determined after acidic hydrolysis. Alternative hydrolysis of the isolated globin with enzyme pronase afforded N-(2-hydroxyethyl)-L-valyl-L-leucine (HEVL) and N-(2-hydroxyethyl)-L-valyl-L-histidine (HEVH), the EO-adducted N-terminal dipeptides of rat globin α- and β-chains, respectively. The ratio of HEVL/HEVH (1:3) reflected higher reactivity of EO with the β-chain. The EO-modified erythrocytes were then given intravenously to the recipient rats. HEVL and HEVH were found to be the ultimate cleavage products excreted in the rat urine. Finally, rats were dosed intraperitoneally with EO, 50 mg/kg. Herein, the initial level of globin-bound HEVL (11.7 ± 1.3 nmol/g) decreased almost linearly over 60 days corresponding to the life span of rat erythrocytes. Daily urinary excretion of HEVL was almost constant for 30-40 days, decreasing faster in the subsequent phase of elimination. Recoveries of the total urinary HEVL from its globin-bound form were 84 ± 6% and 101 ± 17% after administrations of EO and the EO-modified erythrocytes, respectively. In conclusion, urinary HEVL appears to be a promising novel non-invasive biomarker of human exposures to EO.

• MeSH
• Biomarkers urine   MeSH
• Dipeptides metabolism   urine   MeSH
• Erythrocytes MeSH
• Ethylene Oxide toxicity   MeSH
• Globins metabolism   MeSH
• Hydrolysis MeSH
• Rats MeSH
• Leucine MeSH
• Environmental Monitoring MeSH
• Hazardous Substances toxicity   MeSH
• Valine chemistry   MeSH
• Animals MeSH
• Check Tag
• Rats MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH

The study describes the detailed examination of the effect of ethylene oxide sterilization on electrospun scaffolds constructed from biodegradable polyesters. Different fibrous layers fabricated from polycaprolactone (PCL) and a copolymer consisting of polylactide and polycaprolactone (PLCL) were investigated for the determination of their mechanical properties, degradation rates and interaction with fibroblasts. It was discovered that the sterilization procedure influenced the mechanical properties of the electrospun PLCL copolymer scaffold to the greatest extent. No effect of ethylene oxide sterilization on degradation behavior was observed. However, a delayed fibroblast proliferation rate was noticed with concern to the ethylene oxide sterilized samples compared to the ethanol sterilization of the materials.

• MeSH
• Biocompatible Materials chemistry   metabolism   pharmacology   MeSH
• Cell Line MeSH
• Blood Vessel Prosthesis MeSH
• Ethylene Oxide chemistry   pharmacology   MeSH
• Microscopy, Electron, Scanning MeSH
• Elastic Modulus MeSH
• Mice MeSH
• Nanofibers chemistry   MeSH
• Tensile Strength MeSH
• Polyesters chemistry   metabolism   MeSH
• Sterilization MeSH
• Cell Survival drug effects   MeSH
• Animals MeSH
• Check Tag
• Mice MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH

Ethylene oxide (EO), an industrial intermediate and gaseous sterilant for medical devices, is carcinogenic to humans, which warrants minimization of exposure in the workplaces. The principal analytical strategy currently used in biomonitoring of exposure to EO consists in the conversion of N-(2-hydroxyethyl) adduct at the N-terminal valine (HEV) in globin to a specific thiohydantoin derivative accessible to GC-MS analysis (modified Edman degradation, MED). Though highly sensitive, the method is laborious and, at least in our hands, not sufficiently robust. Here we developed an alternative strategy of HEV determination based on acidic hydrolysis (AH) of globin followed directly by HPLC-ESI-MS2 analysis. Limit of quantitation is ca. 25 pmol HEV/g globin. Comparative analyses of globin samples from EO-exposed workers by both the AH-based and MED-based methods provided results that correlated well with each other (R2 > 0.95) but those obtained with AH were significantly more accurate (according to external quality control programme G-EQUAS) and repeatible (5% and 6% for intra-day and between-day analyses, respectively). In conclusion, the new AH-based method surpassed MED being similarly sensitive, much less laborious and more reliable, thus applicable as an effective tool for biomonitoring of EO in exposure control and risk assessment.

• MeSH
• Environmental Biomarkers MeSH
• Ethylene Oxide adverse effects   blood   MeSH
• Globins analysis   MeSH
• Spectrometry, Mass, Electrospray Ionization * MeSH
• Risk Assessment MeSH
• Hydrolysis MeSH
• Occupational Health * MeSH
• Inhalation Exposure * adverse effects   MeSH
• Acids chemistry   MeSH
• Humans MeSH
• Environmental Monitoring methods   MeSH
• Occupational Exposure * adverse effects   MeSH
• Reproducibility of Results MeSH
• Valine analogs & derivatives   blood   MeSH
• Chromatography, High Pressure Liquid * MeSH
• Check Tag
• Humans MeSH
• Male MeSH
• Publication type
• Journal Article MeSH

• MeSH
• Biocompatible Materials radiation effects   MeSH
• Ethylene Oxide MeSH
• Collagen MeSH
• Polyesters MeSH
• Sterilization methods   MeSH
• Materials Testing methods   MeSH
• Publication type
• Research Support, Non-U.S. Gov't MeSH