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Anti-inflammatory properties of micropatterned titanium coatings.

Prolonged inflammation and reactive oxygen species (ROS) generated around an implanted biosensor are the primary causes of the foreign body response, including encapsulation of biosensor membranes. We have previously demonstrated that TiO2 surfaces reduce ROS. Here we investigated the potential of using the anti-inflammatory properties of TiO2 in the design of biosensor membranes with improved long-term in vivo transport properties. Micropatterned Ti films were sputtered onto quartz surfaces in a series of hexagonally distributed dots with identical coverage area of 23% and dot size ranging from 5 to 100 microm. The antioxidant effect of the surfaces was investigated using a cell-free peroxynitrite donor assay and assays of superoxide released from stimulated surface-adhering neutrophils and macrophages. In all three assays, the amount of ROS was monitored using luminol-amplified chemiluminescence. Patterned surfaces in all experimental models significantly decreased ROS compared to the etched surfaces. In the cell-free experiment, the ROS reduction was only dependent on fractional surface coverage. In the cell experiments, however, a dot-size-dependent ROS reduction was seen, with the largest reduction at the smallest dot-size surfaces. These results indicate that micropatterned surfaces with small dots covering only 23% of the surface area exhibit similar antioxidative effect as fully covered surfaces.

Animals↗

Mussel adhesive protein mimetic polymers for the preparation of nonfouling surfaces.

A new biomimetic strategy for modification of biomaterial surfaces with poly(ethylene glycol) (PEG) was developed. The strategy exploits the adhesive characteristics of 3,4-dihydroxyphenylalanine (DOPA), an important component of mussel adhesive proteins, to anchor PEG onto surfaces, rendering the surfaces resistant to cell attachment. Linear monomethoxy-terminated PEGs were conjugated either to a single DOPA residue (mPEG-DOPA) or to the N-terminus of Ala-Lys-Pro-Ser-Tyr-Hyp-Hyp-Thr-DOPA-Lys (mPEG-MAPD), a decapeptide analogue of a protein found in Mytilus edulis adhesive plaques. Gold and titanium surfaces were modified by adsorption of mPEG-DOPA and mPEG-MAPD from solution, after which surface analysis by X-ray photoelectron spectroscopy and time-of-flight secondary ion mass spectroscopy confirmed the presence of immobilized PEG on the surface. The ability of modified surfaces to resist cell attachment was examined by culturing 3T3 fibroblasts on the surfaces for up to 14 days. Quantitative image analysis revealed that cell adhesion to mPEG-DOPA and mPEG-MAPD modified surfaces decreased by as much as 98% compared to control surfaces. Modified Ti surfaces exhibited low cell adhesion for up to 2 weeks in culture, indicating that the nonfouling properties of mPEG-DOPA and mPEG-MAPD treated surfaces persist for extended periods of time. This strategy paradoxically exploits the strong fouling characteristics of MAP analogues for antifouling purposes and may be broadly applied to medical implants and diagnostics, as well as numerous nonmedical applications in which the minimization of surface fouling is desired.

3T3 Cells↗

Expression of cell adhesion complexes in epithelial cells seeded on biomaterial surfaces.

Clinical studies indicate that soft tissue responses around dental implants vary, depending on the material used. It is therefore also possible that there are differences in how epithelial cells attach to various biomaterial surfaces. We studied the adhesion of cultured epithelial cells to five different dental material surfaces and to glass. The efficacy of adhesion was evaluated by using scanning electron microscopy (SEM) and immunofluorescence microscopy (IF) with antibodies to vinculin and alpha(6)beta(4) integrin, two cell surface molecules that are functional in epithelial cell adhesion. Our results indicate that epithelial cells adhere and spread more avidly on metallic surfaces (titanium, Ti(6)Al(4)V titanium alloy, dental gold alloy) than on ceramic surfaces (dental porcelain, aluminum oxide). As revealed by SEM, cells on metallic surfaces had a flattened morphology and formed multicellular islands. On porcelain and aluminum oxide most cells were round and adhesion occurred as single cells. Surface coverage was over twofold on metallic surfaces as compared to ceramic surfaces. IF of cells grown on metallic surfaces revealed vinculin in well-organized focal contacts and alpha(6)beta(4) integrin in punctate patterns typical of prehemidesmosomes. On porcelain and aluminum oxide surfaces the cells were mostly round and showed less well-organized adhesion complexes. Our results indicate that smooth metallic biomaterial surfaces are optimal for epithelial cell adhesion and spreading. These findings may have clinical implications in the design of transgingival implant structures.

Alloys↗

Electrochemical studies on the influence of proteins on the corrosion of implant alloys.

The effect of proteins on corrosion rates of 316L stainless steel, commercially pure titanium and titanium 6-aluminium 4-vanadium was studied in the static and fretting modes. The static mode was studied using cylindrical specimens as per ASTM F-746, and static fracture fixation plates. The fretting mode was studied using a two-hole plate fretting machine which caused a cyclic rocking motion between the plate and the screws, as per ASTM F-897. Electrochemical techniques of polarization resistance and Tafel slope measurements were used to study effects of proteins on the anodic and cathodic corrosion reactions. It was found that proteins increased the corrosion rate of the stainless steel and C.P. titanium cylindrical specimens, but did not have an effect on the Ti-6AI-4V cylinders. In the fretting mode proteins decreased the corrosion rate of the stainless steel plates, but did not have an appreciable effect on either of the titanium alloys. The presence of proteins appeared to cause an increase in the anodic Tafel constant and a decrease in the cathodic Tafel constant of stainless steel specimens. Significant differences in the shapes of the cathodic Tafel slopes were also seen with cylinders with different surface conditions, and static versus fretting plates.

Alloys↗

The economic impact of failures in total hip replacement surgery: 28,997 cases from the Norwegian Arthroplasty Register, 1987-1993.

The Norwegian Arthroplasty Register was established in 1987. Until January 1994, approximately 200 different implant combinations had been used in total hip replacements (THR) in Norway. About 5,500 THR were performed each year in this period with a total cost of 70 million USD per year. We analyzed the economic consequences related to the use of some inferior primary hip arthroplasties in this period. As the reference arthroplasty, we chose the most commonly used prosthesis in Norway, i.e., the Charnley prosthesis fixed with high viscosity cement containing antibiotic and with systemic antibiotic prophylaxis (n 4,970). We compared this reference group to all other primary THR registered in the same time period (n 24,027), and to the following sub-groups of primary THR: 1) uncemented Ti-Fit/ Bio-Fit (acetabulum/femur) combination (n 173), 2) uncemented Coxa/Femora combination (n 153), 3) THR with low-viscosity cement (n 1,807) and 4) THR with Boneloc cement (n 1,250). We estimated the number of additional revisions compared to the reference arthroplasty after a follow-up of 3-5 years in the different groups, with adjustment for age, sex and diagnosis. The direct extra revision costs were calculated. Compared to the reference arthroplasty, the group of all other primary THR gave an extra revision cost estimated at about 1.7 million USD per year. About 1,000 uncemented Bio-Fit femoral prostheses have been applied in Norway, including those implanted before the registration started (1985-1987). The extra revision costs the first postoperative years for these 1,000 prostheses amount to about 0.7 million USD per year. Corresponding figures in the Coxa/ Femora group were 0.08 million USD, in the group with low-viscosity cement, 0.3 million USD and in the Boneloc group, 0.4 million USD per year.

Aged↗

Characteristics of metal and ceramic total hip bearing surfaces and their effect on long-term ultra high molecular weight polyethylene wear.

The micromechanics of ultra high molecular weight polyethylene (UHMWPE) wear in total hip replacement are very complex. Polyethylene wear from the metal head and debris formation are two common types of wear. There are additional wear-related processes occurring at the metal-bearing surfaces that are not well-known, however. This study outlines these processes, including (1) surface wettability changes, (2) oxidative wear of metal surfaces, (3) microabrasion of metal surfaces from oxide film damage, and (4) surface abrasion from three-body polymethylmethacrylate and bone debris. These processes can contribute to metal ion release and a gradual increase in the roughness of the metal surfaces. This can lead to increased long-term UHMWPE wear. Of the metal alloys currently used in total hip replacements, Co-Cr-Mo alloy is significantly more resistant to roughening processes. Hard, stable, oxide: ceramic surfaces articulating against UHMWPE are essentially immune to these surface-roughening processes, however. In addition, they provide a more wettable surface, further minimizing polyethylene wear relative to metal surfaces. By analyzing metal release rates from metal-polyethylene wear tests, it is shown here that Co-Cr-Mo is gradually removed at a rate of about 0.1 micron per year (10(6) cycles), whereas 316L stainless steel is removed on the order of 0.2 microns per year and Ti-6Al-4V on the order of 1 micron per year. The wear rate of Co-Cr-Mo articulating against itself is reported to be still greater, at about 2-4 microns per year after an initial wear-in period. Because metal is gradually removed with articulation time, surface-hardening methods such as nitrogen ion implantation can be expected to provide only temporary resistance to these metal removal and surface-roughening processes. Hard, stable ceramic surfaces such as Al2O3 and ZrO2, however, can be expected to maintain their initial surface finish and thus minimize UHMWPE wear in the long term.

Alloys↗

[Influence of the implant surface on the early phase of osteogenesis in vitro].

The specific structure of a dental implant's surface is often used as an argument for a better overall performance and durability. Nonetheless, it is not yet fully clear to what extent an implant's material or surface structure improves its performance. For a better understanding of the early integration-related processes, growth and initiation of mineralization of human MG-63 osteoblasts grown on glass slides or on polished (MS: machine-surfaced) or structured (SB: deep-structured) titanium surfaces were monitored. Cells were cultured under non-confluent conditions in absence and presence of osteogenic medium (OS). The 3D-architecture of growing cells was documented by confocal laser scanning microscopy (CLSM) upon fluorescently labeling for collagen I. Collagen I distribution was found comparable under all conditions. In control cultures on glass, MS and SB, cells had grown as multilayered but not yet confluent networks, which additionally comprised dome-like structures on the two Ti-surfaces. While on glass and SB cells essentially maintained this architecture also in presence of OS, three-dimensional structures on MS were--if at all--only barely visible. This was reflected also in the protein content of the cultures that was significantly lower under OS in the case of MS only. The activity of the early mineralization marker alkaline phosphatase (ALP) was higher in the controls on glass than on MS or SB. In presence of OS it was significantly higher on MS and SB than in the controls, yet not on glass. Obviously both, the surface material and the surface structure contribute--possibly synergistically--to early processes of implant integration, such as matrix formation and mineralization. The impact of such effects is discussed, in relation to implant loading and implant durability.

Alkaline Phosphatase↗

The resorption rate of atheroma lipids in situ and implanted subcutaneously.

Resorption rates have been investigated in the rabbit for atheroma-lipids and cholesterol injected subcutaneously, atheroma lipids in situ in the mildly atheromatous aorta and lipid in the degenerating peripheral nerve. Atheroma lipids injected subcutaneously resorb relatively rapidly, subcutaneous cholesterol and lipid in Wallerian degeneration are intermediate in this respect, whereas only the group with an initially low blood cholesterol (small than approximately equal to 100 mg/100 ml) showed even a suggestion of lipid resorption from their mild or trivial atheromatous lesions. Ti is not clear whether or not atheroma resorbed at all in the groups with initial blood cholesteroles above 100 mg//00 ml. The relative inertia of the arthromatous lesion is mainly attributed to the relative absence of reticuloendothelial phagocytes in it.

Animals↗

Corrosion behavior of titanium nitride coated Ni-Ti shape memory surgical alloy.

Nickel-titanium (NiTi, nitinol) shape memory alloy was nitrided using an original powder immersion reaction assisted coating (PIRAC) method in order to modify its surface properties. PIRAC nitriding method is based on annealing the samples in the atmosphere of highly reactive nitrogen supplied by decomposition of unstable nitride powders or, alternatively, by selective diffusion of the atmospheric nitrogen to the sample surface. Being a non-line-of-sight process, PIRAC nitriding allows uniform treatment of complex shape surgical implants. Hard two-layer titanium nitride (TiN)/Ti2, Ni coatings were obtained on NiTi surface after PIRAC anneals at 900 and 1000 degrees C. PIRAC coating procedure was found to considerably improve the corrosion behavior of NiTi alloy in Ringer's solution. In contrast to untreated nitinol, no pitting was observed in the samples PIRAC nitrided at 1000 degrees C, 1 h up to 1.1 V. The coated samples were also characterized by very low anodic currents in the passive region and by an exceedingly low metal ion release rate. The research results suggest that PIRAC nitriding procedure could improve the in vivo performance of NiTi alloys implanted into the human body.

Alloys↗

Adsorption/desorption phenomena on pure and Teflon AF-coated titania surfaces studied by dynamic contact angle analysis.

As a result of inflammatory processes, plaque formation on dental titanium implants often leads to clinically pathogenic situations. This special biofilm formation on (bio)materials in contact with saliva is initiated by ionic and protein interactions. In this interfacial process, albumin becomes a main constituent of dental pellicle. Interfacial reactions change the surface characteristics. They determine the following steps of macromolecular adsorption and bacterial adhesion. This work focuses on the dynamic contact angle analysis (DCA), which is a tool for online measurements of dynamic changes of wettability without disturbing the interface during detection. Repeatability of the DCA method has been assessed according to the Bland and Altman method. The kinetics and equilibrium data of shifts in the wetting tension hysteresis indicate ionic influences at the titanium/bovine serum albumin (BSA) interface: the Ca-mediated increase of the BSA adsorption on titanium and the adsorption maximum at the isoelectric point (IEP) of BSA. Ti was surface modified by Teflon AF polymeric coatings. The result of the assessment gives reason to consider Teflon AF as a reference material for DCA repeatability studies. This surface modification caused drastic changes in the dynamic interfacial reactions. Shifts in the wetting tensions during DCA adsorption-desorption experiments clearly demonstrated the partially irreversible adsorption of BSA on Teflon AF. In contrast, reversible adsorption behavior was detected on pure Ti surfaces. These findings strengthen the hypothesis that the analysis of dynamic changes in wetting tension and wetting tension hysteresis is a sensitive analytical method for the detection of dynamic interfacial changes at biomaterial/biosystem interfaces during the initial steps of biofilm formation.

Adsorption↗

Alloying of hydroxyapatite onto Ti6Al-4V by high power laser irradiation.

In the biomedical field, the synthetic hydroxyapatite [Ca(10)(PO)(4)(OH)(2)], with similarity to the inorganic component of bone but brittle, has been considered as the appropriate coating on stronger implant materials, such as metallic implants, for presenting a surface which is conductive to bone formation. Many industrial and laboratory techniques were developed to apply hydroxyapatite onto metallic substrates, such as electrophoretic deposition, ion sputtering, hot isostatic pressing, pulsed laser deposition and the only widely used method commercially available: plasma spraying. This work presents a new approach on how to bind calcium phosphate (CaP) to the Ti alloy with a well-known technique in the metallurgical field: laser surface alloying, in order to overcome the drawbacks of plasma spraying. The analysis of the results obtained and the description of the phenomena that take place in the coating process will complete this explorative study.

Journal Article↗

Metallic wear in failed titanium-alloy total hip replacements. A histological and quantitative analysis.

We conducted extensive histological examination of the tissues that were adjacent to the prosthesis in nine hips that had a failed total arthroplasty. The prostheses were composed of titanium alloy (Ti-6Al-4V) and ultra-high molecular weight polyethylene. The average time that the prosthesis had been in place in the tissue was 33.5 months (range, eleven to fifty-seven months). Seven arthroplasties were revised because of aseptic loosening and two, for infection. In eight hips cement had been used and in one (that had a porous-coated implant for fifty-two months) no cement had been utilized. Intense histiocytic and plasma-cell reaction was noted in the pseudocapsular tissue. There was copious metallic staining of the lining cells. Polyethylene debris and particles of cement with concomitant giant-cell reaction were present in five hips. Atomic absorption spectrophotometry revealed values for titanium of fifty-sic to 3700 micrograms per gram of dry tissue (average, 1047 micrograms per gram; normal, zero microgram per gram), for aluminum of 2.1 to 396 micrograms per gram (average, 115 micrograms per gram; normal, zero micrograms per gram), and for vanadium of 2.9 to 220 micrograms per gram (average, sixty-seven micrograms per gram; normal, 1.2 micrograms per gram). The highest values were found in the hip in which surgical revision was performed at fifty-seven months. The concentrations of the three elements in the soft tissues were similar to those in the metal of the prostheses. The factors to which failure was attributed were: vertical orientation of the acetabular component (five hips), poor cementing technique on the femoral side (three hips), infection (two hips), and separation of a sintered pad made of pure titanium (one hip). A femoral component that is made of titanium alloy can undergo severe wear of the surface and on the stem, where it is loose, with liberation of potentially toxic local concentrations of metal debris into the surrounding tissues. It may contribute to infection and loosening.

Adolescent↗

Structural analysis of hydroxyapatite coatings on titanium.

Hydroxyapatite from two sources was electrophoretically deposited onto flat titanium plate material. Depending upon the deposition conditions various changes in the structure of the ceramic were identified. A well-adhering Ti-P compound was present at the interface. Hydroxyapatite oxygenated to various degrees and tetracalcium phosphate were reproducibly formed in the coating.

Biocompatible Materials↗

Tricuspid valve replacement after cardiac transplantation.

BACKGROUND: Tricuspid valve insufficiency (TI) is common after orthotopic heart transplantation. However, tricuspid valve replacement or repair (TVR) is rare. The aim of this study is to evaluate our experience with TVR in cardiac transplant recipients. METHODS: The Utah Transplantation Affiliated Hospitals (UTAH) Cardiac Transplant Program database was queried for TVR in all adult and pediatric heart transplant recipients. Pre-operative parameters and cardiac hemodynamics were compared with post-operative findings. RESULTS: Since 1985, we identified in our database 17 patients who had 16 TVR, and 2 tricuspid valve repair procedures. Thirty-four heart transplant recipients from the same period were used as controls. The indication for TVR was symptomatic right heart failure (RHF) in 89% of cases, and there was no significant difference between the control group and the surgery group in the average number of biopsies. A flail leaflet was found in 16 cases (89%). One patient died post-operatively due to cardiogenic shock, and 1 patient died 8 months after TVR due to progressive RHF. Improvement in heart failure symptoms was seen in 12 cases. The central venous pressure (CVP) decreased from 17.8 +/- 4.1 mm Hg to 11.0 +/- 7.3 mm Hg (p = 0.013). There was no significant change in cardiac output or renal function. However, the furosemide dose decreased significantly from 47.69 +/- 56.44 mg/day to 26.54 +/- 46.43 mg/day (p = 0.009). CONCLUSIONS: After orthotopic heart transplantation, TVR is a safe and effective procedure to alleviate RHF symptoms. Flail leaflets are the most common operative finding, suggesting that biopsy-induced trauma is the likely cause of severe TI in these patients.

Adult↗

Cell adhesion to biomaterials: correlations between surface charge, surface roughness, adsorbed protein, and cell morphology.

Adhesion of cells to a biomaterial surface can be a major factor mediating its biocompatibility. In this investigation, jet impingement techniques were used to quantify strength of cellular adhesion to various material surfaces. The metals tested: HS25 (a cobalt-based alloy similar to F75), 316L stainless steel, Ti-6Al-4V, and commercially pure tantalum, exhibited nearly a fivefold increase in adhesion strength above that characteristic of the polymeric materials tested (PTFE, silicone rubber, and HDPE). The present study examines physical and biological factors that might influence fibroblast adhesion to the biomaterial surface. The relation between surface charge and cellular adhesion was investigated in a controlled manner by measuring adhesion strength over a range of charge densities. The cells showed charge and electrical potential-dependent adhesion maxima, suggesting that surface alloying for optimum adherence may be possible. In a preliminary series of experiments adsorbed serum protein layers on a series of materials of differing adherence were investigated using gel electrophoresis to assess protein composition. Analysis of adsorbed proteins revealed little difference in relative abundance or total adsorption quantity. SEM micrographs of cells on Ti-6Al-4V and silicone rubber (high and low adhesion materials, respectively) demonstrated differences in cell morphology and cell density.

Biocompatible Materials↗

Bone formation in calcium-phosphate-coated titanium mesh.

The osteogenic activity of porous titanium fiber mesh and calcium phosphate (Ca-P)-coated titanium fiber mesh loaded with cultured syngeneic osteogenic cells was compared in a syngeneic rat ectopic assay model. In 30 syngeneic rats, (Ca-P)-coated and non-coated porous titanium implants were subcutaneously placed either without or loaded with cultured rat bone marrow (RBM) cells. Fluorochrome bone markers were injected at 2, 4, and 6 weeks. The rats were sacrificed, and the implants were retrieved at 2, 4, and 8 weeks post-operatively. Histological analysis demonstrated that none of the (Ca-P)-coated and non-coated meshes alone supported bone formation at any time period. In RBM-loaded implants, bone formation started at 2 weeks. At 4 weeks, bone formation increased. However, at 8 weeks bone formation was absent in the non-coated titanium implants, while it had remained in the (Ca-P)-coated titanium implants. Also, in (Ca-P)-coated implants more bone was formed than in non-coated samples. In general, osteogenesis was characterized by the occurrence of multiple spheres in the porosity of the mesh. The accumulation sequence of the fluorochrome markers showed that the newly formed bone was deposited in a centrifugal manner starting at the center of a pore. Our results show that the combination of Ti-mesh with RBM cells can indeed generate bone formation. Further, our results confirm that a thin Ca-P coating can have a beneficial effect on the bone-generating properties of a scaffold material.

Animals↗

Silicone-specific imaging using an inversion-recovery-prepared fast three-point Dixon technique.

PURPOSE: To demonstrate a new hybrid magnetic resonance imaging (MRI) technique capable of simultaneously generating water-specific and silicone-specific images in a single acquisition. MATERIALS AND METHODS: This technique combines short TI inversion-recovery (STIR) technique for robust fat suppression with an efficient fast spin-echo-based three-point Dixon technique for robust separation of remaining water and silicone in the presence of field inhomogeneities. Images demonstrating the feasibility of the technique were acquired with a 1.5-Tesla scanner in a phantom and in a volunteer with both saline and silicone implants in vivo. RESULTS: The new technique provided water-specific and silicone-specific images of diagnostic quality. Separation of the water and silicone chemical species was complete and satisfactory. Compared with a chemical shift-selective technique, the new technique does not rely heavily on field homogeneity and requires the same or even less scan time to acquire images with similar scan parameters, resolution, and signal-to-noise ratio (SNR). CONCLUSION: The feasibility and potential application of the new technique were demonstrated via imaging a phantom and a silicone breast prosthesis in vivo, and it may be used for more consistent imaging of the silicone implants without compromising the image quality or overall scan time.

Adipose Tissue↗

Determination of metallic ion transfer from an implanted prosthesis by the PIXE method.

Prostheses can release some metallic elements to the surrounding tissues, particularly when they are not covered with a biomaterial layer and when an unsealing process happens. We try to measure major and trace elements in these tissues with an experimentally sensitive method. Proton-induced X-ray emission is used to detect about 10 elements in tissue. Tissues are calcinated and deposited in a thin layer before irradiation. Results are obtained in a standard and samples from three patients. We observe contamination by Ti, Cr, Ni, and Zn in the tissues. Correlations are to be studied between these atomic transfers and prosthesis in the patient.

Hip Prosthesis↗