Isolation of TiNbN wear particles from a coated metal-on-metal bearing: Morphological characterization and in vitro evaluation of cytotoxicity in human osteoblasts.

To improve the wear resistance of articulating metallic joint endoprostheses, the surfaces can be coated with titanium niobium nitride (TiNbN). Under poor tribological conditions or malalignment, wear can occur on these implant surfaces in situ. This study investigated the biological response of human osteoblasts to wear particles generated from TiNbN-coated hip implants. Abrasive particles were generated in a hip simulator according to ISO 14242-1/-2 and extracted with Proteinase K. Particle characteristics were evaluated by electron microscopy and energy dispersive x-ray spectroscopy (EDS), inductively coupled plasma mass spectrometry (ICP-MS) and dynamic light scattering (DLS) measurements. Human osteoblasts were exposed to different particle dilutions (1:20, 1:50, and 1:100), and cell viability and gene expression levels of osteogenic markers and inflammatory mediators were analyzed after 4 and 7 days. Using ICP-MS, EDS, and DLS measurements, ~70% of the particles were identified as TiNbN, ranging from 39 to 94 nm. The particles exhibited a flat and subangular morphology. Exposure to particles did not influence cell viability and osteoblastic differentiation capacity. Protein levels of collagen type 1, osteoprotegerin, and receptor activator of nuclear factor κB ligand were almost unaffected. Moreover, the pro-inflammatory response via interleukins 6 and 8 was minor induced after particle contact. A high number of TiNbN wear particles only slightly affected osteoblasts' differentiation ability and inflammatory response compared to metallic particles. Nevertheless, further studies should investigate the role of these particles in peri-implant bone tissue, especially concerning other cell types.

Cementing techniques for total knee arthroplasty in Norwegian hospitals; a questionnaire-based study.

BACKGROUND: Cementing technique in total knee arthroplasty (TKA) may influence implant survival. There is limited knowledge about the results with clinically used techniques. The aim of this study was to investigate cementing techniques for TKA in Norwegian hospitals, to compare widely used techniques to recommendations from the literature, and to investigate variation within hospitals. METHODS: A questionnaire requesting information about cementing techniques were distributed to all Norwegian orthopedic surgeons performing TKAs regularly in 2020. Data was analyzed using descriptive statistical methods. RESULTS: We acquired 121 responses out of 257 surgeons. They were from 45 out of 56 hospitals, and at least half of the TKA surgeons from 20 hospitals, constituting 79 surgeons. All responders used pulsatile lavage. Cement application to both the tibial plateau and stem (full cementation) was practiced by 61%. Application of cement to both implant and bone was done by 70% of surgeons. Techniques to improve cement penetration were used by 86%. Only 35% of surgeons aimed to get a cement mantle thickness between 3-5 mm. Flexing the knee joint to remove excess cement was done by 82%. We found that in 55% of 20 hospitals the surgeons did not agree on the use of common guidelines in their ward. CONCLUSIONS: The majority of the responders used recommended techniques from the literature when cementing TKA. At more than half of the eligible hospitals, surgeons disagreed about their hospitals' use of common guidelines. Focusing on developing evidence-based guidelines would be beneficial for TKA-quality.

Similarly low blood metal ion levels at 10-years follow-up of total hip arthroplasties with Oxinium, CoCrMo, and stainless steel femoral heads. Data from a randomized clinical trial.

The use of inert head materials such as ceramic heads has been proposed as a method of reducing wear and corrosion products from the articulating surfaces in total hip arthroplasty, as well as from the stem-head taper connection. The aim of the present study was to compare the blood metal ion levels in patients with Oxinium and CoCrMo modular femoral heads, as well as monoblock stainless steel Charnley prostheses at 10 years postoperatively. The 150 patients with osteoarthritis of the hip joint included in a randomized clinical trial were grouped according to femoral head material. One group (n = 30) had received the Charnley monoblock stainless steel stem (DePuy, UK). The other patients (n = 120) received a Spectron EF CoCrMo stem with either a 28 mm CoCrMo or Oxinium modular head (Smith & Nephew, USA). After 10 years, 38 patients had withdrawn, 19 deceased, 7 revised due to aseptic loosening and 5 revised due to infection. The 81 patients with median age of 79 years (70-91) were available for whole blood metal ion analysis. The levels of Co, Cr, Ni and Zr in the blood were generally low with all the head materials (medians <0.3 micrograms/L) and no statistical difference between the groups were found (p = .2-.8). Based on the low blood metal ion values in our study groups, no indication of severe trunnion corrosion in patients with CoCrMo heads was observed, neither was there any beneficial reduction in metal ion exposure with the Oxinium femoral heads.

Inflammatory tissue reactions around aseptically loose cemented hip prostheses: A retrieval study of the Spectron EF stem with Reflection All-Poly acetabular cup.

The cemented Spectron EF stem in combination with the cemented non-crosslinked Reflection All-Poly cup showed a high rate of mid-term aseptic loosening. However, the failure mechanisms are not fully known. We assessed the inflammatory tissue reactions and wear particles in periprosthetic tissues, implant wear and blood metal ion levels in 28 patients with failed implants. Histological analysis showed a macrophage pre-dominant pattern with randomly distributed lymphocytes, with various amounts of neutrophils and giant cells. The number of different cell types in the tissue samples from patients in the cup group and in the stem group was similar. Wear particles, mainly ZrO2 , CoCrMo, and polyethylene particles of different sizes and shapes, were associated with macrophages/giant cells, and total particle load/mm2 was higher in cases of stem loosening. The Spectron EF stems were heavily worn, abraded, and polished. Stem abrasion correlated with metal ion concentrations in blood. The median polyethylene wear rate of the Reflection cups was 0.23 mm/year. The high proximal roughness of the Spectron EF stem resulted in excessive cement wear during loosening. The resulting inflammatory tissue responses to the degradation products both from the cup and the stem led to massive osteolysis and subsequent implant loosening.

Metal ion levels in the blood of patients with metal-on-metal hip prostheses. / Metallionenivåer i blod fra pasienter med metall-mot-metall-hofteprotese.

BACKGROUND: A BHR (Birmingham hip resurfacing) prosthesis was implanted in 445 people in Norway. Adverse reactions can arise as a result of the release of metal ions from metal-on-metal joint surfaces made from cobalt-chromium alloy. The aim of the study was to analyse the release of metal ions during the first five years after surgery in patients with a BHR prosthesis and to investigate whether this was linked to clinical complications. MATERIAL AND METHOD: Forty-four male patients (median age 53 years) implanted with a BHR prosthesis at the Coastal Hospital at Hagevik in the period October 2009 to May 2013 were monitored by means of blood samples before implantation and three months, one year, three years and five years afterwards. Analyses of cobalt and chromium in whole blood were performed. Function scoring was used to clinically assess the prosthetic joint. RESULTS: Metal ion concentrations increased between the surgery date and one year later (p < 0.001), and subsequently remained stable. After five years, the median concentrations (min.- max.) of cobalt and chromium were 1.1 µg/L (0.4-6.3 µg/L) and 1.4 µg/L (0.4-11.7 µg/L) respectively for unilateral prostheses (n = 36), and 2.3 µg/L (1.6-28.5 µg/L) and 2.6 µg/L (1.7-14.1 µg/L) respectively for bilateral prostheses (n = 8). Five patients underwent revision surgery, while other patients had good hip function. INTERPRETATION: Patients with a BHR prosthesis had a significant increase in cobalt and chromium in their blood one to five years after surgery, but the median levels were still well below the threshold value of 7 µg/L, which indicates an increased risk of complications.

Corrosion and metal release from overlapping arterial stents under mechanical and electrochemical stress - An experimental study.

Intra-arterial stenosis due to atherosclerosis is often treated with endovascular balloon dilatation with a metal stent. Restenosis is common and is frequently treated with a new stent placed inside the existing one or the stents are placed with overlap to cover a larger area of the vessels. Observations of stent fractures, stent compression, accumulation of immunocompetent cells around stents have suggested the possibility of immunologic reactions to substances released from stents. An accelerated corrosion model was developed to study corrosion behaviour of commonly used surgical peripheral stents. Single nitinol stents (n = 6), connected stents of the same material (stent-in-stent, both nitinol, n = 7) and connected stents of dissimilar alloys (Nitinol with stainless steel stent inside, n = 7) were investigated. The stents were subjected to mechanical pulsatile radial strain (up to 8% strain at 1 Hz) and electrochemical stress (+112 mV vs. SCE). The release of nickel and titanium ions was compared. Scanning electron images were obtained. There was a higher release of nickel when combining two similar (range: 1382-8018 µg/L, p = 0.0012) and dissimilar (range: 170-2497 µg/L, p = 0.0023) stents compared to single stents (range: 0.4-216 µg/L). The concentration of titanium was low (range: 1.6-98.4 µg/L) with only a difference between the single and two similar stents (p = 0.0047). Deposits of corrosion products were clearly visible after fretting and pitting corrosion mainly on the Nitinol stents. Several mesh wires were fractured. The study demonstrated that mechanical strain combined with weak electric potential resulted in pronounced corrosion and fracture of stents, especially with overlapping stents. Single stents after pulsatile load released the lowest amount of ions. The combination of stents of the same material (Nitinol) had the highest release of metal ions.

Label-Free Monitoring of Uptake and Toxicity of Endoprosthetic Wear Particles in Human Cell Cultures.

The evaluation of the biological effects of endoprosthetic wear particles on cells in vitro relies on a variety of test assays. However, most of these methods are susceptible to particle-induced interferences; therefore, label-free testing approaches emerge as more reliable alternatives. In this study, impedance-based real-time monitoring of cellular viability and metabolic activity were performed following exposure to metallic and ceramic wear particles. Moreover, label-free imaging of particle-exposed cells was done by high-resolution darkfield microscopy (HR-ODM) and field emission scanning electron microscopy (FESEM). The isolated human fibroblasts were exposed to CoCr28Mo6 and alumina matrix composite (AMC) ceramic particles. HR-ODM and FESEM revealed ingested particles. For impedance measurements, cells were seeded on gold-plated microelectrodes. Cellular behavior was monitored over a period of 48 h. CoCr28Mo6 and AMC particle exposure affected cell viability in a concentration-dependent manner, i.e., 0.01 mg/mL particle solutions led to small changes in cell viability, while 0.05 mg/mL resulted in a significant reduction of viability. The effects were more pronounced after exposure to CoCr28Mo6 particles. The results were in line with light and darkfield microcopy observations indicating that the chosen methods are valuable tools to assess cytotoxicity and cellular behavior following exposure to endoprosthetic wear particles.

Novel Nanoparticulate and Ionic Titanium Antigens for Hypersensitivity Testing.

Titanium is used in a wide variety of materials ranging from medical devices to materials used in everyday life. Adverse biological reactions that could occur in patients, consumers, and workers should be monitored and prevented. There is a lack of available agents to test and predict titanium-related hypersensitivity. The aim of this study was to develop two bioavailable titanium substances in ionic and nanoparticulate form to serve as antigens for hypersensitivity testing in vitro. Peripheral blood mononuclear cells from 20 test subjects were stimulated with the antigens and secretion of monocytic and lymphatic cytokines and chemokines were measured by a multiplex bead assay. Lymphocyte stimulation indices were also determined in a subset of test subjects by measuring CD69 and HLA-DR expression by flow cytometry. Cytokine profiling revealed that both antigens increased production of typical monocyte and macrophage secreted cytokines after 24 h, with significant increases in IL-1ß, IL-7, IL-10, IL-12, IL-2R, IL-6, GM-CSF, TNF-α, IL-1RA, MIP-1α, MIP-1ß, IFN-α, and IL-15. Lymphatic cytokines and chemokines were not significantly induced by activation. After seven days of stimulation, ionic-Ti (2.5 µg/mL) caused proliferation (stimulation index > 2) of CD4+ cells and CD8+ cells in all persons tested (N = 6), while titanium dioxide nanoparticles (50 µg/mL) only caused significant proliferation of CD4+ cells. Our preliminary results show that the experimental titanium antigens, especially the ionic form, induce a general inflammatory response in vitro. A relevant cohort of test subjects is required to further elucidate their potential for predictive hypersensitivity testing.

Early aseptic loosening of a mobile-bearing total knee replacement.

Background and purpose - Registry-based studies have reported an increased risk of aseptic tibial loosening for the cemented Low Contact Stress (LCS) total knee replacement compared with other cemented designs; however, the reasons for this have not been established. We made a retrieval analysis with the aim of identifying the failure mechanism. Patients and methods - We collected implants, cement, tissue, blood, and radiographs from 32 failed LCS Complete cases. Damage to the tibial baseplate and insert was assessed. Exposure to wear products was quantified in 11 cases through analysis of periprosthetic tissue and blood. Implant alignment and bone cement thickness was compared with a control group of 43 non-revised cases. Results - Loosening of the tibial baseplate was the reason for revision in 25 retrievals, occurring at the implant-cement interface in 16 cases. Polishing was observed on the lower surface of the baseplate and correlated to the level of cobalt, chromium, and zirconium in the blood. No evidence of abnormally high polyethylene wear was present. For each 1 mm increase in cement thickness the odds of failure due to aseptic loosening decreased by 61%. Greater varus alignment was associated with a shorter time to failure. The roughness, Ra, of a new LCS baseplate's lower surface was 3.7 (SD 0.7) µm. Interpretation - Debonding of the tibial component at the implant-cement interface was the predominant cause of tibial aseptic loosening. A thin cement layer may partly explain the poor performance. Furthermore, the comparatively low tibial surface roughness and the lack of a keeled stem may have played a role in the failures observed.

The Impact of Metal Ion Exposure on the Cellular Behavior of Human Osteoblasts and PBMCs: In Vitro Analyses of Osteolytic Processes.

Osteolysis in the periprosthetic tissue can be caused by metallic wear particles and ions that can originate from implant surface corrosion. These products influence cellular behavior and stimulate the expression of proinflammatory cytokines. The purpose of this study was to evaluate the impact of CoCr29Mo6 ions on cell survival, differentiation, and cytokine expression in human osteoblasts and peripheral blood mononuclear cells (PBMCs). Thus, we exposed cells with a mixture of 200 µg/L ion solution and determined cell viability and apoptosis/necrosis. Gene expression analyses of osteoblastic and osteoclastic differentiation markers as well as pro-osteolytic mediators (IL-6, IL-8, TNF-α, MCP-1, MMP1, TIMP1) were performed. These markers were also investigated in mixed cultures of adherent and non-adherent PBMCs as well as in co-cultures of human osteoblasts and PBMCs. The ion solution induced necrosis in osteoblasts and PBMCs in single cultures. All examined mediators were highly expressed in the co-culture of osteoblasts and PBMCs whereas in the single cell cultures only IL-6, IL-8, and MMP1 were found to be stimulated. While the applied concentration of the CoCr29Mo6 ion solutions had only marginal effects on human osteoblasts and PBMCs alone, the co-culture may provide a comprehensive model to study osteolytic processes in response to Co and Cr ions.

Impact of Maternal Selenium Status on Infant Outcome during the First 6 Months of Life.

Pregnant women and infants are at risk for selenium deficiency, which is known to have negative effects on immune and brain function. We have investigated selenium levels in 158 healthy never-pregnant women and in 114 pregnant and lactating women and their infants at age 6 months and related this to clinical outcomes during the first 6 months of life. Neurodevelopment was assessed with the parental questionnaire Ages and Stages (ASQ) at 6 months. A maternal selenium level ≤0.90 µmol/L in pregnancy week 18 was negatively related to infant neurodevelopment at 6 months (B = -20, p = 0.01), whereas a selenium level ≤0.78 µmol/L in pregnancy week 36 was associated with an increased risk (odds ratio 4.8) of having an infant infection during the first 6 weeks of life. A low maternal selenium status in pregnancy was found to be associated with an increased risk of infant infection during the first 6 weeks of life and a lower psychomotor score at 6 months. We suggest a cutoff for maternal serum selenium deficiency of 0.90 µmol/L in pregnancy week 18 and 0.78 µmol/L in pregnancy week 36. This should be reevaluated in an intervention study.

Wear particles and ions from cemented and uncemented titanium-based hip prostheses-a histological and chemical analysis of retrieval material.

Wear debris-induced inflammation is considered to be the main cause for periprosthetic osteolysis in total hip replacements (THR). The objective of this retrieval study was to examine the tissue reactions and exposure to metal ions and wear particles in periprosthetic tissues and blood samples from patients with titanium (Ti)-based hip prostheses that were revised due to wear, osteolysis, and/or aseptic loosening. Semiquantitative, histological tissue evaluations in 30 THR-patients revealed numerous wear debris-loaded macrophages, inflammatory cells, and necrosis in both groups. Particle load was highest in tissues adjacent to loosened cemented Ti stems that contained mainly submicron zirconium (Zr) dioxide particles. Particles containing pure Ti and Ti alloy elements were most abundant in tissues near retrieved uncemented cups. Polyethylene particles were also detected, but accounted only for a small portion of the total particle number. The blood concentrations of Ti and Zr were highly elevated in cases with high abrasive wear and osteolysis. Our findings indicate that wear particles of different chemical composition induced similar inflammatory responses, which suggests that particle size and load might be more important than the wear particle composition in periprosthetic inflammation and osteolysis.

Coordinating retrieval and register studies improves postmarket surveillance.

BACKGROUND: The relative risk of revision of the Titan(®) femoral stem due to aseptic loosening increased after 2000; however, the reasons for this have not been established. A retrieval analysis was initiated with the aim of delineating the failure mechanism. QUESTIONS/PURPOSES: We asked whether aseptic loosening in stems after 2000 was associated with (1) appearance of osteolytic lesions, (2) wear particle exposure, (3) stem damage, or (4) changes to the implant or surgical instrumentation. METHODS: Femoral stems, cement, tissue, and radiographs were collected from 28 patients. We assessed the development of osteolytic lesions in 17 patients. Exposure to wear particles was quantified in 18 patients. Stem damage was assessed in 15 patients. We observed differences in the implants by examination of 24 retrieved stems. Information concerning changes to instrumentation was requested from the manufacturer. RESULTS: We found osteolysis in all patients receiving implants after 2000, which was associated with a median dose of cement and stem particles of 14,726/mm(2). Abrasion covered 59% of the surface of stems implanted from 1999. We identified geometric changes to the stem, the percent weight of aluminum in the stem's oxide layer decreased from 25% to 14% after 1997 and the rasp used to prepare the femoral cavity changed to a broach in 1999. CONCLUSIONS: Stems implanted from 2000 failed through osteolysis induced by particles released from the cement and implant. Changes to implant geometry, surface oxide layer, and surgical tools occurred in the same time frame as the reduction in survivorship.

Formation of potential titanium antigens based on protein binding to titanium dioxide nanoparticles.

Degradation products of titanium implants include free ions, organo-metallic complexes, and particles, ranging from nano to macro sizes. The biological effects, especially of nanoparticles, is yet unknown. The main objective of this study was to develop Ti-protein antigens in physiological solutions that can be used in testing of cellular responses. For this purpose, 0.1% TiO2 nanoparticles less than 100 nm were mixed with human serum albumin (HSA), 0.1% and 1%, in cell culture medium (DMEM, pH 7.2). The Ti concentrations in the resulting solutions were analyzed by inductively coupled plasma mass spectrometry. The stability of the nanoparticles in suspension was analyzed by UV-vis spectrophotometer and Dynamic Light Scattering. The concentration of Ti in suspension was dependent on the presence and concentration of HSA. Albumin prevented high aggregation rate of TiO2 nanoparticles in cell culture medium. It is shown that nano TiO2-protein stable aggregates can be produced under physiological conditions at high concentrations, and are candidates for use in cellular tests.

Should the galvanic combination of titanium and stainless steel surgical implants be avoided?

It is recommended that one should not combine different metals in orthopaedic devices. The least noble metal in such a galvanic coupling is more likely to corrode. However, some studies have failed to show increased corrosion when titanium and stainless steel are combined. The aim of this study was to determine the fretting corrosion of the contact areas between screws and plates made of these dissimilar metals used for internal fixation of bone fractures. The plates were fixed to a bone-simulating material and subjected to tensile and compressive forces in both human serum and Hank's solution. The outcome variables included in the analyses were weight loss, and release of Ti, Cr, Ni and Mo to the different media. Results from the multiple combinations were subjected to multivariate statistics. Principal component analysis visualised our findings and allowed classification of similar samples and separation of discrepant groups of samples. We found a significant effect of the test medium, but no dramatic effect due to mixing of metals. The titanium screws and plates corroded more in serum than in saline, while the opposite was true for stainless steel. Combination of dissimilar screws and plates did not cause higher weight loss or metal release than the single-material constructions, indicating comparable clinical safety.

Copper, zinc, and selenium in human blood and urine after injection of sodium 2,3-dimercaptopropane-1-sulfonate: a study on subjects with dental amalgam.

This study investigated the effects of a single dose of intravenously administered sodium 2,3-dimercaptopropane-1-sulfonate (DMPS) on the essential elements copper, zinc, and selenium in human blood and urine. The possible role of dental amalgam was also addressed. Eighty individuals, divided in four groups according to the presence or absence of dental amalgam fillings and symptoms self-related to such fillings, were given DMPS (2 mg/kg body wt) and 500 mL Ringer's acetate intravenously. Urine and blood were collected prior to the injection, and thereafter at intervals over a 24-h period. Cu, Zn, and Se concentrations were determined by atomic absorption spectrometry methods. A statistically significant increase in the concentrations of Cu and Zn in urine was observed 30 and 120 min after the DMPS injection compared to the preinjection concentrations. The concentrations of Se were not affected. The cumulated excretion over 24 h after DMPS injection constitutes only from 0.1% to 0.7% of the body content of these elements. There was no effect of different amalgam statuses on Cu and Zn excretion. We found a temporary decrease (4-7%) in the concentrations of Cu, Zn, and Se in blood 15 and 30 min after DMPS, but this seems to be the result of dilution factors. Administration of a single dose of DMPS does not affect the body stores of the essential elements Cu, Zn, and Se.

Dental amalgam affects urinary selenium excretion.

Selenium may have a protective effect against mercury toxicity. The aim of the present study was to investigate if selenium excretion in urine was affected in persons with dental amalgam fillings. The reason for this study is that dental amalgam is the most important source of inorganic mercury exposure in the general population, although the potential toxic effects of this exposure remain a subject for debate. The chelating agent 2,3 dimercaptopropane-1-sulfonate (DMPS) was injected intravenously (2 mg/kg) to provoke metal excretion. Urine samples were subsequently collected at intervals over a 24-h period. Selenium concentration was determined by hydride-generation atomic absorption spectrometry. The study was comprised of 20 persons who claimed symptoms from dental amalgam and 21 healthy persons with amalgam fillings. There were two control groups without amalgam. One control group had amalgam replaced because of concern about illness resulting from mercury release (n = 20), whereas the other control group never had amalgam (n = 19). Individuals with amalgam excreted less selenium (36.4 microg, median value) over 24 hours than those without amalgam (47.5 microg) (p = 0.016). There was no difference in selenium excretion between groups with (42.4 microg) and without (39.4 microg) amalgam-related symptoms (p = 0.15). The findings indicate that individuals exposed to low levels of elemental mercury from dental amalgam excrete less selenium to urine than unexposed individuals.