One-year performance of thin-strut cobalt chromium sirolimus-eluting stent versus thicker strut stainless steel biolimus-eluting coronary stent: a propensity-matched analysis of two international all-comers registries.

OBJECTIVES: Recent improvements in coronary stent design have focussed on thinner struts, different alloys and architecture, more biocompatible polymers, and shorter drug absorption times. This study evaluates safety and efficacy of a newer generation thin-strut cobalt chromium sirolimus-eluting coronary stent (SES, Ultimaster) in comparison with a second-generation thicker strut stainless steel biolimus-eluting stent (BES, Nobori) in percutaneous coronary intervention (PCI) practice. METHODS: A propensity score analysis was performed to adjust for differences in baseline characteristics of 8137 SES patients and 2738 BES patients of two PCI registries (e-Ultimaster and NOBORI 2). An independent clinical event committee adjudicated all endpoint-related adverse events. RESULTS: The use of SES, as compared with BES was associated with a significantly lower rate of myocardial infarction (MI) (1.2% vs 2.2%; P = 0.0006) and target vessel-related MI (1.1% vs 1.8%; P = 0.002) at 1 year. One-year composite endpoints of all predefined endpoints were lower in patients undergoing SES implantation (target lesion failure: 3.2% vs 4.1%; P = 0.03, target vessel failure: 3.7% vs 5.0%; P = 0.003, patient-oriented composite endpoint 5.7% vs 6.8%; P = 0.03). No significant differences between SES and BES were observed in all-cause death (2.0% vs 1.6%; P = 0.19), cardiac death (1.2% vs 1.2%; P = 0.76) or stent thrombosis (0.6% vs 0.8%; P = 0.43). CONCLUSIONS: These findings suggest an improved clinical safety and efficacy of a newer generation thin-strut SES as compared with a second-generation thicker strut BES.

One-Year Clinical Outcome of Inspiron Stent in All-Comers Population (Analysis from 790 Consecutive Patients).

AIMS: The goal of this study was to evaluate the performance of the InspironTM coronary stent (Scitech Medical™, Goiás, Brazil). The InspironTM sirolimus-eluting stent uses an ultrathin L-605 cobalt-chromium alloy with a 75 µm strut thickness platform coated with an abluminal biodegradable polymer. The polymer is eliminated from the body through the tricarboxylic acid cycle in 6-9 months, releasing 80% of the drug within 30 days after its deployment. METHODS: It was a prospective, single-center registry. To represent clinical practice, all patients undergoing percutaneous coronary intervention were included in this registry. There were no exclusion criteria. Clinical follow-ups were performed at twelve months. The endpoints were the occurrence of all-cause death, definite stent thrombosis, and new revascularization. RESULTS: Between November 2017 and May 2019, 790 patients were included (1067 lesions). The mean age was 60.42 ± 14.94 years, and 74.7% presented with acute coronary syndrome. Diabetes mellitus was present in 43.9% of patients, and previous myocardial infarction and previous percutaneous coronary intervention were present in 17.9% and 11.3%, respectively. Angiographic success was achieved in 99.1%. The incidence of all-cause death was 11.5% (6.2% in-hospital and 5.3% in the follow-up) and definitive stent thrombosis was 0.2%. New revascularization was performed in only 5.8% (target lesion revascularization: 2.2%; progression of disease in another lesion: 3.6%). Based on the multivariate regression analysis, only chronic renal failure was an independent predictor of adverse events (OR: 3.3; 95% CI: 1.22-8.92). CONCLUSION: The result of this single-center registry demonstrates the safety and excellent performance of the InspironTM stent in daily clinical practice with a low rate of adverse cardiac events.

Electrochemically reduced graphene oxide on CoCr biomedical alloy: Characterization, macrophage biocompatibility and hemocompatibility in rats with graphene and graphene oxide.

Electrochemically reduced graphene oxide (ErGO) films on a biomedical grade CoCr alloy have been generated and characterized in order to study their possible application for use on joint prostheses. The electrodeposition process was performed by cyclic voltammetry. The characterization of the ErGO films on CoCr alloys by XPS revealed sp2 bonding and the presence of CO and CO residual groups in the graphene network. Biocompatibility studies were performed with mouse macrophages J774A.1 cell cultures measured by the ratio between lactate dehydrogenase and mitochondrial activities. An enhancement in the biocompatibility of the CoCr with the ErGO films was obtained, a result that became more evident as exposure time increased. Macrophages on the CoCr with the ErGO were well-distributed and conserved the characteristic cell shape. In addition, vimentin expression was unaltered in comparison with the control, results that indicated an improvement in the CoCr biocompatibility with the ErGO on the material surface. The in vivo response of graphene and graphene oxide was assessed by intraperitoneal injection in wistar rats. Red blood cells are one of the primary interaction sites so hemocompatibility tests were carried out. Rats inoculated with graphene and graphene oxide showed red blood cells of smaller size with a high content in hemoglobin.

Local Biological Reactions and Pseudotumor-Like Tissue Formation in relation to Metal Wear in a Murine In Vivo Model.

Metal wear debris and released ions (CoCrMo), which are widely generated in metal-on-metal bearings of hip implants, are also found in patients with metal-on-polyethylene bearings due to the mechanically assisted crevice corrosion of modular taper junctions, including head-neck and neck-stem taper interfaces. The resulting adverse reactions to metal debris and metal ions frequently lead to early arthroplasty revision surgery. National guidelines have since been published where the blood metal ion concentration of patients must consistently be monitored after joint replacement to prevent serious complications from developing after surgery. However, to date, the effect of metal particles and metal ions on local biological reactions is complex and still not understood in detail; the present study sought to elucidate the complex mechanism of metal wear-associated inflammation reactions. The knee joints in 4 groups each consisting of 10 female BALB/c mice received injections with cobalt chrome ions, cobalt chrome particles, and ultra-high-molecular-weight polyethylene (UHMWPE) particles or PBS (control). Seven days after injection, the synovial microcirculation and knee joint diameter were assessed via intravital fluorescence microscopy followed by histological evaluation of the synovial layer. Enlarged knee diameter, enhanced leukocyte to endothelial cell interactions, and an increase in functional capillary density within cobalt chrome particle-treated animals were significantly greater than those in the other treatment groups. Subsequently, pseudotumor-like tissue formations were observed only in the synovial tissue layer of the cobalt chrome particle-treated animals. Therefore, these findings strongly suggest that the cobalt chrome particles and not metal ions are the cause for in vivo postsurgery implantation inflammation.

Mitigation of monocyte driven thrombosis on cobalt chrome surfaces in contact with whole blood by thin film polar/hydrophobic/ionic polyurethane coatings.

Monocytes are active at the crossroads between inflammation and coagulation processes since they can secrete pro-inflammatory cytokines and express tissue factor (TF), a major initiator of coagulation. Cobalt-chrome (CoCr), a metal alloy, used as a biomaterial for vascular stents, has been shown to be potentially pro-thrombotic and pro-inflammatory. Research work with a polymer from a family of degradable-polar hydrophobic ionic polyurethanes (D-PHI), called HHHI, has been shown to exhibit anti-inflammatory responses from human monocytes. We have generated multifunctional polyurethane thin films (MPTF) based on the HHHI chemistry, as a thin coating for CoCr and have evaluated the reactivity of blood with MPTF-coated CoCr. The results showed that the coating of CoCr with MPTF derived from HHHI prevents thrombin generation, reduces coagulation activation, and suppresses fibrin formation in whole blood. Activation of monocytes was also suppressed at the surface of MPTF-coated CoCr and specifically the decrease in thrombin generation was accompanied by a significant decrease in TF and pro-inflammatory cytokine levels. Mass spectroscopy of the adsorbed proteins showed lower levels of fibrinogen, fibronectin and complement C3, C4, and C8 when compared to CoCr. We can conclude that MPTFs reduce the pro-thrombotic and pro-inflammatory phenotype of monocytes and macrophages on CoCr, and prevent clotting in whole blood.

Assessment of corrosion in retrieved spine implants.

Recently the use of dissimilar metals in spine instrumentation has increased, especially in the case of adult deformities, where rods made from Cobalt Chrome alloys (CoCr) are used with Titanium (Ti) screws. The use of dissimilar metals increases the risk of galvanic corrosion and patients have required revision spine surgery due to severe metallosis that may have been caused by corrosion. We aimed to assess the presence of corrosion in spine implant retrievals from constructs with two types of material combinations: similar (Ti/Ti) and dissimilar (CoCr/Ti). First, we devised a grading score for corrosion of the rod-fixture junctions. Then, we applied this score to a collection of retrieved spine implants. Our proposed corrosion grading score was proven reliable (kappa > 0.7). We found no significant difference in the scores between 4 CoCr and 11 Ti rods (p = 0.0642). There was no indication that time of implantation had an effect on the corrosion score (p = 0.9361). We recommend surgeons avoid using implants designs with dissimilar metals to reduce the risk of corrosion whilst a larger scale study of retrieved spine implants is conducted. Future studies can now use our scoring system for spine implant corrosion. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 106B: 632-638, 2018.

The induction of CXCR4 expression in human osteoblast-like cells (MG63) by CoCr particles is regulated by the PLC-DAG-PKC pathway.

BACKGROUND: Osteolysis which leads to aseptic loosening of implants is a fundamental problem in joint replacement surgery (arthroplasty) and the leading cause for implant failure and revision surgery. Metal (CoCr) particles separated from implants by wear cause osteolysis and the failure of orthopedic implants, but the molecular mechanism is not clear. The chemokine receptor CXCR4 has been shown to play a pivotal role in periprosthetic osteolysis. The aim of this study was to determine which signal transduction pathway (PLC-DAG-PKC or MAPK/ERK) induces CXCR4 expression in osteoblast-like cells (MG63) cells. METHODS: MG63 and Jurkat cells were stimulated with different amounts of particles (107 , 106 , and 105 ) for different time periods (30 min to 24 h), in the presence and absence of specific inhibitors (chelerythrine for the PLC-DAG-PKC pathway and PD98059 for the MAPK/ERK pathway). The expression of CXCR4-specific mRNA was determined by real-time polymerase chain reaction (PCR), and the PKC activity was measured by Western Blot using an antibody specific for PKC-related phosphorylation. RESULTS: Real-time PCR data showed that CXCR4 mRNA expression in MG63 cells induced by CoCr particles was significantly diminished by the PKC-specific inhibitor chelerythrine. This effect was not observed with the MAPK/ERK inhibitor PD98059. The involvement of PKC was also confirmed by an intensified phosphorylation pattern after stimulation with CoCr particles. In Jurkat cells, none of the inhibitors exhibited any effect. CONCLUSION: The induction of CXCR4-specific mRNA expression in MG63 cells after stimulation with CoCr particles is regulated by the PLC-DAG-PKC pathway and not by the MAPK/ERK pathway. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 105B: 2326-2332, 2017.

Biological responses of preosteoblasts to particulate and ion forms of Co-Cr alloy.

This study compared the particulate and ion forms of a cobalt-chrome (Co-Cr) alloy on the differentiation/activation of preosteoblasts. Mouse preosteoblasts (MC3T3-E1) were cultured in an osteoblast-induction medium in the presence of particulate and ion forms of a Co-Cr alloy, followed by cell proliferation and cytotoxicity evaluations. The maturation and function of osteoblasts were assessed by alkaline phosphatase (ALP) assay and related gene expressions. Both particulate and ion forms of the metals significantly reduced the proliferation of MC3T3-E1 cells in a dose-dependent manner. Similarly, cells challenged with high concentrations of particles and ions exhibited a marked cytotoxic effect and diminished expression of ALP. Real-time (RT) polymerase chain reaction (PCR) data have suggested that cells with Co-Cr particles dramatically promoted over-expression of monocyte chemo-attractant protein-1 (MCP-1), tumor necrosis factor-α (TNF-α), and interleukin-6 (IL-6), whereas Co(2+) ions treatment predominately up-regulated expressions of receptor activator of nuclear factor kappa-B ligand (RANKL), nuclear factor of activated T-cells cytoplasmic 1 (NFATc1), and down-regulated expression of osteoprotegerin (OPG) and Osterix (Osx). Overall, this study provides evidence that both Co-Cr alloy particles and metal ions interfered with the MC3T3-E1 cells for their growth, maturation, and functions. Further, Co-Cr particles exhibited stronger effects on inflammatory mediators, while metal ions showed more influence on inhibition of osteoblast differentiation and promotion of osteoclastogenesis.

Bacterial and osteoblast behavior on titanium, cobalt-chromium alloy and stainless steel treated with alkali and heat: a comparative study for potential orthopedic applications.

HYPOTHESIS: Anatase-modified titanium (Ti) substrates have been found to possess antibacterial properties in the absence of ultraviolet irradiation, but the mechanism is not known. We hypothesize that this is due to the bactericidal effects of reactive oxygen species (ROS) generated by the surface anatase. EXPERIMENTS: Alkali and heat treatment was used to form anatase on Ti surface. The generation of ROS, and the behavior of bacteria and osteoblasts on the anatase-modified Ti were investigated. Cobalt-chrome (Co-Cr) alloys and stainless steel (SS) were similarly treated with alkali and heat, and their surface properties and effects on bacteria and osteoblasts were compared with the results obtained with Ti. FINDINGS: The anatase-functionalized Ti substrates demonstrated significant bactericidal effects and promoted apoptosis in osteoblasts, likely a result of ROS generated by the anatase. The alkali and heat-treated Co-Cr and SS substrates also reduced bacterial adhesion but were not bactericidal. This effect is likely due to an increase in hydrophilicity of the surfaces, and no significant ROS were generated by the alkali and heat-treated Co-Cr and SS substrates. The treated Co-Cr and SS substrates did not induce significant apoptosis in osteoblasts, and thus with these properties, they may be promising for orthopedic applications.

Effects of Ti, PMMA, UHMWPE, and Co-Cr wear particles on differentiation and functions of bone marrow stromal cells.

This study investigates the roles of orthopedic biomaterial particles [Ti-alloy, poly(methyl methacrylate) (PMMA), ultrahigh-molecular-weight polyethylene (UHMWPE), Co-Cr alloy] on the differentiation and functions of bone marrow stromal cells (BMSCs). Cells were isolated from femurs of BALB/c mice and cultured in complete osteoblast-induction medium in presence of micron-sized biomaterial particles at various doses. 3-(4,5)-Dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide assay and lactate dehydrogenase assay were performed for cell proliferation and cytotoxicity. Differentiation and function of osteoblasts were evaluated by alkaline phosphatase (ALP), osteocalcin, RANKL, OSX, and Runx2 expressions. Murine interleukin-1 (IL-1), IL-6, and tumor necrosis factor-α in culture media were determined by enzyme-linked immunosorbent assay. Challenge with low doses of Ti, UHMWPE, or Co-Cr particles markedly promoted the bone marrow cell proliferation while high dose of Co-Cr significantly inhibited cell growth (p < 0.05). Cells challenged with low dose of PMMA or UHMWPE particles (0.63 mg/mL) exhibited strong ALP activity, whereas Ti and Co-Cr groups showed minimal effects (p < 0.05). UHMWPE and Ti particles also promoted higher expression of proinflammatory cytokines. Real-time polymerase chain reaction data suggested that cells treated with low dose (0.5 mg/mL) particles resulted in distinctly diminished RANKL expression compared to those exposed to high concentrated (3 mg/mL) particles. In conclusion, various types of wear debris particles behaved differently in the differentiation, maturation, and functions of osteogenic cells; and the particulate debris-interacted BMSCs may play an important role in the pathogenesis and process of the debris-associated aseptic prosthetic loosening.

Biocompatibility effects of indirect exposure of base-metal dental casting alloys to a human-derived three-dimensional oral mucosal model.

OBJECTIVES: The study employed a three-dimensional (3D) human-derived oral mucosal model to assess the biocompatibility of base-metal dental casting alloys ubiquitous in fixed prosthodontic and orthodontic dentistry. METHODS: Oral mucosal models were generated using primary human oral keratinocyte and gingival fibroblast cells seeded onto human de-epidermidised dermal scaffolds. Nickel-chromium (Ni-Cr) and cobalt-chromium (Co-Cr) base-metal alloy immersion solutions were exposed to oral mucosal models for increasing time periods (2-72h). Analysis methodologies (histology, viable cell counts, oxidative stress, cytokine expression and toxicity) were performed following exposure. RESULTS: Ni-based alloy immersion solutions elicited significantly decreased cell viability (P<0.0004) with increased oxidative stress (P<0.0053), inflammatory cytokine expression (P<0.0077) and cellular toxicity levels (P<0.0001) compared with the controls. However, the Ni-free Co-Cr-based alloy immersion solutions did not elicit adverse oxidative stress (P>0.4755) or cellular toxicity (P<0.2339) responses compared with controls. CONCLUSIONS: Although the multiple analyses highlighted Ni-Cr base-metal alloy immersion solutions elicited significantly detrimental effects to the oral mucosal models, it was possible to distinguish between Ni-Cr alloys using the approach employed. The study employed a 3D human-derived full-thickness differentiated oral mucosal model suitable for biocompatibility assessment of base-metal dental casting alloys through discriminatory experimental parameters. CLINICAL SIGNIFICANCE: Increasing incidences of Ni hypersensitivity in the general population warrants serious consideration from dental practitioners and patients alike where fixed prosthodontic/orthodontic dental treatments are the treatment modality involved. The novel and analytical oral mucosal model has the potential to significantly contribute to the advancement of reproducible dental medical device and dental material appraisals.

The concentrations of IL-8 and IL-6 in gingival crevicular fluid during nickel-chromium alloy porcelain crown restoration.

We explored gum irritation and cytotoxicity caused by nickel-chromium (Ni-Cr) alloy porcelain by interleukin-8 (IL-8), interleukin-6 (IL-6) and gingival crevicular fluid (GCF) volumes at different time points peri-crown restoration. This prospective study was conducted in 60 young adults. The total amount and concentrations of IL-8 and IL-6 per site, GCF volumes, and blood neutrophil counts were performed prior to and at 1 week, 3 months, and 6 months after Ni-Cr alloy-porcelain crown restoration. Thirty male and 30 female subjects, aged 20-35 years old were enrolled. The total amount and concentrations of IL-8 and IL-6 per site, GCF volumes increased after nickel-chromium (Ni-Cr) alloy-porcelain crown restoration, and reached its peak at the third month as the GCF volume increased by 52.20 %, the total amount and concentrations of IL-8 increased by 112.11 and 22.75 %; the total amount and concentrations of IL-6 increased by 77.66 and 17.17 % when compared to baseline. In particular, the increase of IL-8 concentration was found in female patients at 3 months after restoration; while the neutrophil count of the peripheral blood did not change significantly. The increase in the total amount and the concentrations of IL-8 and IL-6 and GCF volume may be related to the cytotoxicity induced by Ni-Cr alloy. The significant increase of IL-8 concentration in females indicates that more attention should be given to women during Ni-Cr alloy porcelain crown restoration.

Osteoblastic potency of bone marrow cells cultivated on functionalized biometals with cyclic RGD-peptide.

The fixation of cementless endoprostheses requires excellent fixation at the bone implant interface. Although the surface structures of these implants are designed to promote osteoblastic differentiation, poor bone quality may prevent or delay osseointegration. There is evidence that RGD peptides known as recognition motifs for various integrins, promote cellular adhesion, influence cellular proliferation, and differentiation of local cells. In this study, five different metal surfaces were analyzed: Sandblasted (TiSa) and polished (TiPol) Ti6Al4V, porocoated (CCPor) and polished (CCPol) cobalt chrome and polished stainless steel (SS) were coated by ethanol amine and poly(ethylene glycol) to attach covalently RGD peptides. Human mesenchymal stromal cells of healthy donors were cultivated onto prior functionalized metal surfaces for 14 days without osteogenic stimulation. Cell proliferation and differentiation were quantitatively evaluated for native (I), NaOH pre-activated (II), NaOH pre-activated, and PEG-coated (III) as well as for RGD (IV) coated surfaces. The RGD immobilization efficiency was analyzed by epi-fluorescence spectroscopy, cell morphology was documented by light and scanning electron microscopy. The RGD-binding efficiency was TiSa > TiPol > SS > CCPor > CCPol. RGD coated surfaces showed the highest average cell proliferation on CCPol > SS > CCPor > TiSa ≥ TiPol, whereas cellular differentiation mostly correlated with the observed proliferation results, such as CCPol > TiSa > SS > CCPor > TiPol. Considering statistical analyses (significance level of α = 0.05), the RGD-coating of all biometals in comparison and in respect of their particular controls showed no significant improvement in cellular proliferation and osteoblastic differentiation.

Development of a discriminatory biocompatibility testing model for non-precious dental casting alloys.

OBJECTIVES: To develop an enhanced, reproducible and discriminatory biocompatibility testing model for non-precious dental casting alloys, prepared to a clinically relevant surface finishing condition, using TR146 oral keratinocyte cells. METHODS: Comparative biocompatibility was determined following direct and indirect exposure of TR146 cells to two nickel-chromium (Ni-Cr) and a cobalt-chromium (Co-Cr) alloy-discs. The surface roughness of the discs was determined using a contact stylus profilometer and the elemental ion release by inductively coupled plasma mass spectrometry (ICP-MS). Subsequent biocompatibility analysis included cell morphology, cell density measurements with Trypan blue exclusion assay, inflammatory cytokine expression with ELISAs, cellular metabolic activity using XTT and cellular toxicity using lactate dehydrogenase (LDH) release assay. RESULTS: TR146 cell morphology was altered following direct and indirect exposure to the Ni-Cr alloys but not the Co-Cr alloy. Significant reductions (all P<0.001) in viable cell density measurements, cellular metabolic activity, significant increases inflammatory cytokine expression and cellular toxicity were observed when TR146 cells were exposed to the Ni-Cr alloys. Significant decreases in cell density measurements, cellular metabolic activity, significant increases inflammatory cytokine expression and cellular toxicity for the Ni-Cr d.Sign(®)15 alloy compared with d.Sign(®)10 alloy were identifiable (all P<0.001). Cellular toxicity was attributed to nickel ion release levels in solution detected by ICP-MS analysis. DISCUSSION: Nickel ions from the Ni-Cr alloys permeated the epithelial cells and activated a proinflammatory response, namely IL-1a, IL-8 and PGE2 expression. Further evidence of nickel ioninduced cell death was supported by the decreased biocompatibility of the highest nickel ion releasing alloy (d.Sign(®)15 compared with d.Sign(®)10) and the increased biocompatibility of the Co-Cr (d.Sign(®)30) alloy where nickel ions were absent.

Five-year comparison of oxidized zirconium and cobalt-chromium femoral components in total knee arthroplasty: a randomized controlled trial.

BACKGROUND: In vitro analysis has shown that oxidized zirconium on ultra-high molecular weight polyethylene has better wear properties than cobalt-chromium on ultra-high molecular weight polyethylene. The purpose of this study was to determine if oxidized zirconium femoral components performed better than cobalt-chromium in vivo and if the use of oxidized zirconium components had clinical adverse effects. METHODS: Forty consecutive patients (eighty knees) underwent simultaneous bilateral cruciate-retaining total knee arthroplasty for primary osteoarthritis from January 2002 to December 2003. For each patient, the knees were randomized to receive the oxidized zirconium femoral component, with the contralateral knee receiving the cobalt-chromium component. Outcome measures included the Western Ontario and McMaster Universities Osteoarthritis Index, Knee Injury and Osteoarthritis Outcome Score, Knee Society score, and British Orthopaedic Association patient satisfaction scale. Radiographic outcomes include the Knee Society total knee arthroplasty roentgenographic evaluation and scoring system and measurement of radiographic wear. Patients and assessors were blinded to the treatment groups and results. RESULTS: There were no significant differences in clinical, subjective, and radiographic outcomes between the two implants at five days, six weeks, and one, two, or five years postoperatively. At five years following surgery, 38% of the patients preferred the cobalt-chromium knee compared with 18% who preferred the oxidized zirconium knee (p = 0.02) and 44% had no preference. CONCLUSIONS: Five-year outcomes after total knee arthroplasty with oxidized zirconium and cobalt-chromium femoral components showed no significant differences in clinical, subjective, and radiographic outcomes. Patients had no preference or preferred the cobalt-chromium prosthesis to the oxidized zirconium prosthesis at the time of the five-year follow-up. There were no adverse effects associated with the use of oxidized zirconium femoral implants.

Cellular responses to cobalt-chrome and CP titanium--an in vitro comparison of frameworks for implant-retained oral prostheses.

The responses of cell types in peri-implant tissues to cobalt-chrome and titanium were studied in vitro. Cylinders were made from both a cobalt-chrome alloy and commercially pure titanium (length 6 mm, diameter 7.9 mm). Plastic tubes were placed over the cylinders to create cell culture wells, in which human epithelial cells or mouse fibroblasts were cultivated. Cell viability was studied using the Alamar Blue method. The surface structure of two samples of each material was analyzed with optical interferometry. The morphology of cells grown on cylinders of each material was studied with scanning electronic microscopy. Epithelial cells and fibroblasts in the titanium group were more viable than those in the cobalt-chrome group (p = 0.001 and p = 0.000, respectively). The titanium surfaces had a greater height deviation (S(a), p = 0.027) but were less dense (S(ds), p = 0.044) than the cobalt-chrome group. The scanning electronic microscopy revealed no major deviations from normal cell morphology. Within the limitations of the present study, the findings indicate that epithelial cells as well as fibroblasts have a stronger negative response to cobalt-chrome alloy than to titanium. We suggest that these differences can be explained only bythe material per se and not by the minor differences in surface structure. Further and clinical studies are needed to confirm the significance of these findings.

Intravascular ultrasound assessment of cobalt chromium versus stainless steel drug-eluting stent expansion.

It is not clear whether the thin struts and different alloy of a cobalt chromium stent will cause greater acute stent recoil compared to conventional stainless steel stents. We used postintervention intravascular ultrasound (IVUS) examinations to study 99 patients with 116 stented lesions: 61 Xience/Promus stents (cobalt chromium stent group) and 27 Taxus Liberté and 28 Cypher stents (stainless steel stent group). The IVUS images were obtained before and immediately after stent implantation with only the stent-delivery balloon. The ratio of the IVUS-measured to manufacturer-predicted stent diameter and area was the measure of acute stent recoil and expansion. The baseline patient characteristics, lesion morphology, and procedural details were comparable between the 2 groups. The ratio of the IVUS-measured to manufacturer-predicted stent diameter and area was 0.74 versus 0.73 (p = 0.57) and 0.63 versus 0.63 (p = 0.69), respectively, for the cobalt chromium and stainless steel stents. In conclusion, the acute performance of Xience/Promus was similar to that of previous stainless steel stents, and the thinner cobalt chromium metallic platform did not compromise the radial strength of the stent.

Low dose metal particles can induce monocyte/macrophage survival.

Aseptic loosening results in pain, loss of function, and ultimately prosthetic joint failure and revision surgery. The generation of wear particles from the prosthesis is a major factor in local osteolysis. We investigated the effects of such wear particles on the survival of monocytes and macrophages, populations implicated in wear particle-driven pathology. Particles from titanium aluminum vanadium (TiAlV) and cobalt chromium (CoCr) alloys were generated in-house and were equivalent in size (0.5-3 microm) to those seen in patients. Human CD14(+) monocytes and murine bone marrow-derived macrophages (BMM) were treated with TiAlV and CoCr particles in vitro, and cell survival was assayed. Both particles increased monocyte and macrophage survival in a dose-dependent manner, with an optimal concentration of around 10(7) particles/mL. Conditioned media from particle-treated BMM also increased macrophage survival. Studies with antibody blockade and gene-deficient mice suggest that particle-induced BMM survival is independent of endogenous CSF-1 (M-CSF), GM-CSF, and TNFalpha. These data indicate that wear particles can promote monocyte/macrophage survival in vitro possibly via an endogenous mediator. If this phenomenon occurs in vivo, it could mean that increased numbers of macrophages (and osteoclasts) would be found at a site of joint implant failure, which could contribute to the local inflammatory reaction and osteolysis.

The effect of UV-photofunctionalization on the time-related bioactivity of titanium and chromium-cobalt alloys.

This study examined the possible changes in the bioactivity of titanium surfaces during their aging and investigated the effect of ultraviolet (UV) light treatment during the age-related change of titanium bioactivity. Rat bone marrow-derived osteoblastic cells were cultured on new titanium disks (immediately after either acid-etching, machining, or sandblasting), 4-week-old disks (stored after processing for 4 weeks in dark ambient conditions), and 4-week-old disks treated with UVA (peak wavelength of 365 nm) or UVC (peak wavelength of 250 nm). During incubation for 24 h, only 50% of the cells were attached to the 4-week-old surfaces as compared to the new surface. UVC treatment of the aged surface increased its cell attachment capacity to a level 50% higher than the new surfaces, whereas UVA treatment had no effect. Proliferation, alkaline phosphatase activity, and mineralization of cells were substantially lower on the 4-week-old surfaces than on the new surfaces, while they were higher on the UVC-treated 4-week-old surfaces as compared to the new surfaces. The age-related impaired bioactivity was found on all titanium topographies as well as on a chromium-cobalt alloy, and was associated with an increased percentage of surface carbon. Although both UVA and UVC treatment converted the 4-week-old titanium surfaces from hydrophobic to superhydrophilic, only UVC treatment effectively reduced the surface carbon to a level equivalent to the new surface. Thus, this study uncovered a time-dependent biological degradation of titanium and chromium-cobalt alloy, and its restoration enabled by UVC phototreatment, which surmounts the innate bioactivity of new surfaces, which is more closely linked to hydrocarbon removal than the induced superhydrophilicity.

Macrophages detoxify the genotoxic and cytotoxic effects of surgical cobalt chrome alloy particles but not quartz particles on human cells in vitro.

Particles of surgical cobalt chrome alloy are cytotoxic and genotoxic to human fibroblasts in vitro. In vivo orthopaedic patients are exposed to cobalt chrome particles as a result of wear of a joint replacement. Many of the wear debris particles that are produced are phagocytosed by macrophages that accumulate at the site of the worn implant and are disseminated to local and distant lymph nodes the liver and the spleen. In this study we have tested whether this process of phagocytosis could have altered the cytotoxic and genotoxic properties of the cobalt chrome particles. Quartz particles have been investigated as a control. Micron-sized particles of cobalt chrome alloy were internalised by either white cells of peripheral blood or by THP-1 monocytes for 1 week and 1 day, respectively. The particles were then extracted and presented at different doses to fibroblasts for 1 day. There was a reduction of the cytotoxicity and genotoxicity of the cobalt chrome particles after phagocytosis by white cells or THP-1 cells. Cobalt chrome particles that were internalised by fibroblasts also showed a reduction of their cytotoxicity but not their genotoxicity. In contrast the cytotoxicity and genotoxicity of quartz particles was increased after internalisation by THP-1 cells. The surface morphology of the cobalt chrome particles but not the quartz particles was changed after phagocytosis by THP-1 cells. This study suggests that the genotoxic and cytotoxic properties of particles that fall within the size range for phagocytosis may be highly complex in vivo and depend on the combination of material type and previous phagocytosis. These results may have relevance for particle exposure from orthopaedic implants and from environmental or industrial pollution.