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Identification of titanium in human tissues: probable role in pathologic processes.

Six cases of titanium dioxide exposure involving lung, skin, and synovium are described, with a review of the literature. The patients, four men and two women, were between the ages of 22 and 65 years. The pulmonary changes were characterized by fibrosis and numerous macrophages with abundant deposition of a black pigment. Adjacent areas of bronchopneumonia were also observed. In the skin a severe necrotizing lesion involving the subcutaneous tissue with extension to the muscle was observed in one case and a nonspecific inflammatory response was observed in another; both cases showed abundant black pigment deposition. Electron microscopy and energy dispersive x-ray analysis demonstrated the presence of large quantities of titanium in the pigment granules. There may be a combination of black pigment deposition and fibrosis, necrosis, or a xanthomatous or granulomatous reaction, that, together with negative results on special staining and culture studies for organisms, should raise the suspicion of titanium-associated injury and prompt the study of the affected tissues by x-ray analysis for positive identification.

Adult↗

Porcelain bond to laser-welded titanium surfaces.

OBJECTIVES: The purpose of this investigation was to determine if laser-welding titanium had an effect on the bond strength of porcelain to metal. This is an important consideration since the metal copings for many multi-unit porcelain restorations are fabricated as single units and then either soldered or welded. METHODS: The bond strength of porcelain to laser-welded titanium was measured with a four-point bending test and the interface was examined using SEM/EDX analysis. RESULTS: The result showed no statistically significant differences (p<0.05) in bond strengths between laser-welded surfaces and mechanically machined surfaces and neither were there any alterations in composition identified after the welding. The use of a special bonding agent did not improve the bond strength significantly. SIGNIFICANCE: Fusing porcelain to laser-welded areas in titanium fixed restorations implies no deterioration of bond strength.

Barium↗

Accelerated oxide growth on titanium implants during autoclaving caused by fluorine contamination.

Titanium implants were occasionally found to be strongly discoloured after autoclaving. The discolouration is shown to be due to an accelerated growth of the surface oxide that covers the implants. Oxide thicknesses up to 650 A have been observed, i.e. more than ten times thicker than on normal implants. By applying surface sensitive spectroscopies (SIMS and XPS or ESCA) it is also shown that these oxide films contain considerable amounts of fluorine, alkali metals and silicon. Screening tests with alkali-halide solutions identify fluorine as the impurity responsible for the accelerated oxide growth. Discolouration after autoclaving can be observed for fluorine contaminations down to the ppm level. In those cases where discolouration was observed in the clinical situation, the source of fluorine was the textile cloths in which the titanium implant storage box had been wrapped during the autoclaving procedure. The cloths contained residual Na2SiF6 which had been used as an additive to the rinsing water used in the last step of the cloth laundry procedure. Since the biocompatibility of titanium implants is closely related to their surface oxides it is advisable to avoid all sources of fluorine in the implant preparation procedures.

Color↗

Interface analysis of titanium and zirconium bone implants.

A thin layer of titanium or zirconium was evaporated onto the surface of a plastic implant which was then inserted in the rabbit tibial metaphysis for six months. The implants and surrounding bone were cut out en bloc and sectioned for phase contrast microscopy, scanning- and transmission-electron microscopy. The intact bone-to-metal interface in the case of titanium revealed a fibrous tissue-free boundary zone with a 200-400 A thick proteoglycan coat immediately adjacent to the titanium oxide. Thereafter collagen filaments were seen and, at approximately 1000 A from the interface, collagen bundles. The tissues surrounding the zirconium-coated implant consisted of a 300-500 A thick proteoglycan layer, followed by a zone with collagen filaments and collagen bundles, not closer to the zirconium oxide than a few thousand A.

Animals↗

Wear of ion-implanted pure titanium against UHMWPE.

Six specimens were manufactured from commercially pure titanium (grade IV) to resemble femoral head prostheses, and five of them ion implanted to increase the wear properties. Together with three cobalt-chrome controls they were run for one million cycles on a 10-station joint simulator. For the first time both the polymer and metallic wear were quantified in the same study. The purpose of the investigation was to estimate the potential for using commercially pure titanium as a bearing surface against ultrahigh-molecular-weight polyethylene for total joint application. It was concluded that the wear properties of titanium were improved by ion implantation, and that these positive effects could probably be enhanced with development of a better polishing technique, and by finding methods of extending the penetration depth of the nitrogen ions.

Biocompatible Materials↗

Qualitative interfacial study between bone and tantalum, niobium or commercially pure titanium.

Tantalum (Ta), niobium (Nb) and commercially pure titanium (c.p. Ti) were sputtered on to the surfaces of polycarbonate plastic implants. After 3 month of insertion, in the tibial metaphysis of rabbits, the implants were removed with a surrounding bone collar and processed for light (LM) and electron microscopy (EM). By EM a zone of ground substance tens of nanometers wide without collagen filaments was noticed surrounding the Ta implants. Multinucleated macrophages could occasionally be recognized in the interface zone. Foreign body reactions were more striking at the Nb interface while no multinucleated macrophages were observed in the c.p. Ti interface. The ground substance layer had a thickness in the range of 40-60 nm for the Nb implants, whereas in c.p. Ti sections the collagen filaments were noticed 20-40 nm from the metal surface. There are more subtle differences between tantalum and c.p. titanium than between c.p. titanium and niobium which seems to be less well tolerated when implanted in bone.

Animals↗

Surface analysis of titanium implants.

Medical grade titanium samples were examined using X-ray photoelectron spectroscopy before and after immersion in various proteins. Additionally, an implant removed from a patient following clinical failure was examined using scanning ion and electron microscopy. The surface of the as-received samples was found to be mainly TiO2, with contaminants of H2O/OH-, calcium and nitrogen which remained after autoclaving. The immersed proteins adhered to the titanium surface, possibly via a Ca-O link. The failed clinical sample was found to be partially fibrously encapsulated with evidence of calcification. Small amounts of TiOOH were detected at the fibrous periphery, supporting the theory of Tengvall and co-workers that in vivo titanium implants are covered in a gel of this material.

Bone and Bones↗

Tissue response to titanium implants in experimental antigen-induced arthritis.

The healing of threaded, non-alloyed titanium implants in bone was studied in an experimental model of monoarticular arthritis in New Zealand white rabbits. Immunization with bovine serum albumin (BSA) and repeated intra-articular injections with BSA elicited an immune response and clinical signs of inflammation. Implants were inserted and 6 wk after surgery, with full weight-bearing, the rabbits were killed by perfusion fixation. Light microscopic morphometry showed that the cartilage was thinner and the subchondral bone had a lower density in the arthritic joints compared to the control side. The titanium implants in the arthritic joints had a lesser degree of mineralized bone-implant contact and surrounding bone than the implants inserted in control joints. The present study shows that the healing of titanium implants in the rabbit knee joint is impaired in experimental immunologic arthritis. This model may be useful for the study of biomaterial-tissue interactions under pathological conditions.

Animals↗

Titanium with different oxides: in vitro studies of protein adsorption and contact activation.

Adsorption of albumin (HSA) and fibrinogen (Fib) from human blood plasma onto titanium surfaces with varying oxide properties was studied with an enzyme-linked immunosorbent assay. The intrinsic activation of blood coagulation (contact activation) was studied in vitro using a kallikrein-sensitive substrate. The sample surfaces were characterized with Fourier transform Raman spectroscopy. Auger electron spectroscopy and atomic force microscopy. Low Fib and high HSA adsorption was observed for all titanium samples except for the radio frequency plasma-treated and water-incubated samples, which adsorbed significantly lower amounts of both. Oxide thickness and carbon contamination showed no influence on protein adsorption or contact activation. Smooth samples with a surface roughness (Rrms) < 1 nm showed some correlation between surface wettability and adsorption of Fib and HSA, whereas rough surfaces (Rrms > 5 nm) did not. To varying degrees, all titanium surfaces indicated activation of the intrinsic pathway of coagulation as determined by their kallikrein formation in plasma.

Adsorption↗

Uptake and biodistribution of 99mtechnetium methylene-[32P] diphosphonate during endosteal healing around titanium, stainless steel and hydroxyapatite implants in rat tibial bone.

Early evaluation of intraosseous implant success and failure is critical, but, until now, there have been no reliable systems of measurement. The present study assessed whether the use of 99mtechnetium methylene-[32P]diphosphonate (99mTcMD32P), a marker for both bone formation and mineralization, can indicate if an implant is bone-bonding or non-bonding. Moreover, this study examined how bone-bonding (titanium and hydroxyapatite) and non-bonding (stainless steel) implants affected the normal healing of bone after marrow ablation, as measured by uptake of 99mTc and 32P. Titanium, hydroxyapatite and stainless steel implants were placed in the right tibiae of Sabra strain rats following ablation of the marrow, and 99mTcMD32P was injected 18 h before harvest. AT 3, 6, 14, 21 and 42 d (and in some experiments, on days 28 and 35) post-injury, the treated and contralateral tibiae were removed and cleaned of soft tissue. The uptake of 99mTc and 32P was measured in the whole bone, as well as in its organic and inorganic phases. Effects of the implants were assessed by comparing the treated to the untreated tibia in each rat. The distribution of 99mTc and 32P varied with each implant. After the insertion of titanium, increased 99mTc uptake was seen in whole bone and in the inorganic and organic phases at days 6-14. 32P uptake in whole bone and in the inorganic phase increased only at day 6, and 32P uptake was decreased in the organic phase at that time. In tibiae implanted with hydroxyapatite, 99mTc and 32P uptake was seen in the whole bone at days 6 and 14. While 99mTc uptake was increased in both the organic and inorganic phases, 32P uptake into the organic phase was decreased at both day 6 and day 14. In tibiae implanted with stainless steel, effects were observed only on day 6. The increased 99mTc uptake in whole bone reflected increases in both the organic and mineral phases. Increased 32P uptake was observed in whole bone as well, due to an increase in the 32P uptake in the mineral phase only; incorporation of 32P in the organic phase was comparable to that found in the contralateral limb. The results of this study indicate that implants alter bone healing, as indicated by the uptake of 99mTc and 32P in the different bone compartments. Moreover, decreased 32P uptake by the organic phase in the presence of bone-bonding implants suggests that cleavage of 99mTcMD32P into its technetium and methylene diphosphonate moieties was inhibited, perhaps as a function of the onset of calcification in the newly synthesized osteoid. The effect of the implants on bone healing was observed on days 6-14, when active bone formation and mineralization were occurring, supporting the hypothesis that these materials events associated with initial calcification. Uptake of 99mTc varies as a function of time, and uptake of 32P varies with time and distribution in the mineral or organic phase of bone, suggesting that these parameters may be useful as indicators of bone-bonding.

Animals↗

Presence of multinucleated giant cells around machined, sandblasted and plasma-sprayed titanium implants: a histological and histochemical time-course study in rabbit.

A histological and histochemical evaluation was conducted in rabbit to study the presence of multinucleated giant cells (MGCs) at the interface with machined, sandblasted and plasma-sprayed titanium implants. No MGCs were observed, at any of the experimental times, around machined and sandblasted titanium surfaces. MGCs were, on the contrary, present at the interface with titanium plasma-sprayed implants at two weeks and at two months. At two weeks these cells were numerous, and in some areas, particularly around the spires, tended to line almost all the implant perimeter surface. MGCs were present in large numbers where bone was present at the interface, while, on the contrary, where there was no newly formed bone, they tended to be fewer in number and smaller in diameter. At four and eight weeks these cells tended to decrease in number. The histochemical staining for acid phosphatase (ACP) and alkaline phosphatase (ALP) showed that MGCs were negative to ACP, while many ALP-positive osteoblasts, actively secreting osteoid matrix, were in close and tight contact with the MGCs. In no case was an inflammatory infiltrate present in connection with the MGCs. The precise nature of MGCs is still not clear, but our histological and histochemical results could point to a priming effect on the activity of the osteoblasts in a similar way to the supposed role of the osteoclasts.

Animals↗

Influence of the surface structure of titanium materials on the adhesion of fibroblasts.

Of utmost importance for the successful use of an implant is a good adhesion of the surrounding tissue to the biomaterial. In addition to the surface composition of the implant, the surface topography also influences the properties of the adherent cells. The aim of this investigation was thus to study the influence of the surface structure of the substrate on the formation of focal contacts and on the orientation of cultivated gingival fibroblasts by means of fluorescence microscopy. A further goal was to determine the effect of the material composition on the cell shape, on the assumption that in each case a lengthening of the cells can be expected to provide a more favourable adhesion behaviour than a spherical cell shape. In order to describe the shape of the cell, a shape factor was defined which was calculated from the area covered by the cells and from their circumference. To determine the influence of the surface structure, substrate platelets of cp-titanium, TiAl6V4 and TiTa30 were ground. Onto these specimens human gingival fibroblasts of the 5th to 7th passages were cultivated. After a culture time of two days the cells were fixed and stained. The number of orientated cells was determined as a function of the surface roughness of the substrate. The number of orientated cells was shown to increase---independent of the material---with increasing roughness of the ground substrate. On a polished surface the number of orientated cells was 11% (average peak-to-valley height 0.04 microns); at a peak-to-valley height of 1.36 microns the number of orientated cells increased to 72%. It could be observed that the orientated cells had a higher density of focal contacts where they were in contact with the edges of the grinding grooves. In order to determine the effect of the surface composition, gingival fibroblasts were cultured for 14 d on polished substrate specimens of cp-titanium, TiAl6V4 and TiTa30 and examined for differences in shape. The cells grown on cp-titanium and on TiTa30 had shape factors of 1.76 and 1.58 respectively, whereas those grown on TiAl6V4 had a shape factor of 0.93. The unfavourable spherical shape of the fibroblasts (resulting in a poor adhesion) grown on TiAl6V4 after a culture period of 14 d may be the result of a locally increased vanadium concentration in the substrate, with an accompanying increase in the release of toxic vanadium ions.

Alloys↗

Mutagenicity testing of condensates of smoke from titanium dioxide/hexachloroethane and zinc/hexachloroethane pyrotechnic mixtures.

Condensates of smoke from titanium dioxide/hexachloroethane and zinc/hexachloroethane pyrotechnic mixtures were investigated for their potential to produce genetic damage in the tester strains TA98, TA100, TA1535 and TA1537 of Salmonella typhimurium and in the mouse bone marrow micronucleus assay. Both smoke condensates contained several chlorinated hydrocarbons among which tetrachloroethylene, hexachloroethane, hexachlorobutadiene and hexachlorobenzene were identified by GC/MS. Condensate of smoke from titanium dioxide/hexachloroethane showed a dose-related positive response in the Salmonella assay with strains TA98 and TA100 in the absence of metabolic activation from rat liver S9 fraction. Both smoke condensates were negative in the micronucleus assay but produced a small but significant depression of erythropoietic activity. The results indicate that smoke condensate from titanium dioxide/hexachloroethane mixtures contains unidentified compound(s) that may be considered mutagenic in the Salmonella assay.

Animals↗

Titanium mesh (TiMesh) osteosynthesis: a fast and adaptable method of semi-rigid fixation.

Titanium mesh has been used in the USA for the fixation of fractures of the facial skeleton since the Vietnam war. Despite the increasing use of titanium mesh osteosynthesis for trauma, orthognathic and reconstructive surgery in the USA, it is only in recent years that it has gained acceptance in Europe. This paper appraises the original titanium mesh osteosynthesis system (TiMesh) in a wide range of surgical contexts in the maxillofacial region. It has been found to be quick and reliable in placement, highly adaptable and to have considerably reduced the operating time. Its further potential advantages in reducing stress-shielding and improving functional bone healing due to its semi-rigid nature are discussed.

Bone Screws↗

Physico-chemical considerations of titanium as a biomaterial.

Physico-chemical properties of titanium are discussed. Special attention is paid to those of amorphous TiO 2 that contact tissues in vivo. In aqueous environments TiO 2. (aq) has low ion-formation tendency and low reactivity with macromolecules. This is accompanied by low toxicity. Titanium does not facilitate reactive oxygen radical generation during inflammatory conditions as observed in in-vitro experiments. The outermost layers of the oxide are in the Ti(IV) oxidation state, although using electron spin resonance (ESR) techniques, formation of Ti(III) is observed at atmospheric conditions. The impact of similarities between water and TiO 2 is speculated upon, and the physico-chemical properties of titanium are tentatively linked to some in-vivo consequences.

Biocompatible Materials↗

Comparative study of hydroxyapatite and titanium dental implants in dogs.

This study compares the clinical performances and histologic response in dogs to a cylindrical implant with a surface consisting of dense hydroxyapatite (HA) and a threaded titanium implant in functionally loaded and unloaded conditions. Implantation was performed in five dogs, which were killed at 2 or 4 months postfunctional condition (4 or 6 months after implantation). Clinical evaluation showed that neither implant demonstrated significant movement, and assessment of gingival inflammation and sulcus depth showed no significant differences between them. After axial sectioning, the titanium implants were easily removed from the bone, whereas the HA-coated implants were adherent to the bone. Histologically, both implants showed osteogenic ingrowth to the surface in functional and nonfunctional conditions. High-magnification scanning electron micrographs of plastic sections showed that a portion of the interface between the HA-coated implant and the bone showed no gap, whereas gaps were observed at all interfaces with the titanium implant. Histomorphometric analysis by light microscopy indicated that there was no significant difference in the percent bone contact length. Clinically, the two implants behaved similarly.

Alveolar Process↗

Effect of hydroxyapatite on bone formation around exposed heads of titanium implants in rabbits.

Dense hydroxyapatite (HA)--collagen was placed around the protruding heads of titanium and titanium alloy implants in the femurs of 38 rabbits. After 6 months, bone apposition was evaluated by gross examination and scanning electron microscopy. Although bone was observed in direct contact with the implant heads, the extremities of the implant heads were surrounded by connective tissue. Compared with the control animals, packing dense HA-collagen around the implant heads did not increase the area of osteogenesis. When the implants penetrated into bone through previously placed HA-collagen blocks, there was a decrease in the amount of bone attached to the body of the implants compared with the controls. The results of this study suggest that the use of dense HA does not increase the amount of bone tissue formed around titanium implants.

Alloys↗

Properties of a titanium nitride coating for dental instruments.

Adhesion of tooth-coloured restorative materials to the instruments used to place them is a clinical problem. This paper examines the low-stick properties and the durability of a 5 micron coating of titanium nitride on stainless steel when used with two composites (a hybrid and a microfilled) and a glass polyalkenoate (ionomer) cement. Titanium nitride-coated dies were compared to polished stainless steel for adhesion to the unset restorative material before and after a period of wear, and also for properties of surface hardness, contact angle with unfilled resin and frictional coefficient. The results demonstrated that, while the coated instruments were significantly harder and showed a lower coefficient of friction and a higher contact angle with resin, they were slightly 'stickier' than highly polished stainless steel, and this difference persisted even after wear. However, the material is very hard, resistant to damage, and appears to have little potential to discolour the restorative materials with which it is used. It is concluded that a titanium nitride coating confers no additional advantage as regards low-stick properties, over clean, polished stainless steel used for dental instruments.

Adhesiveness↗