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Histologic evaluation of the osseous adaptation to titanium and hydroxyapatite-coated titanium implants.

The aim of this study was to obtain more information about the bone reaction to titanium and hydroxyapatite (HA)-coated titanium implants during the first 3 months after implantation. Therefore, uncoated and coated implants were inserted into the tibia of rabbits for various implantation periods. The histological results demonstrated that although there were no marked differences in bony reaction at the cortical level to the different implant materials, HA-coating appeared to induce more bone formation in the medullary cavity. It was also noted, that 3 months after insertion loss of coating thickness had occurred.

Animals↗

[Management of craniofacial bone defects with individually prefabricated titanium implants. Follow-up and evaluation of 78 patients with 78 titanium implants 1994-1998].

STUDY: From 1994 to 1998, 78 prefabricated titanium implants were used for the reconstruction of large and complex cranial and craniofacial defects in 76 patients at 19 European centres. After a mean follow-up of 8 months, a clinical and radiological examination was used to determine the results of the reconstruction and the patients' satisfaction. Using a standardized questionnaire patients were also able to comment, subjectively, on improvements or alterations after the insertion of the implant. RESULTS: Two implants were removed after an early infectious complication and in a another two cases the implants were removed in order to obtain a tissue sample for histological examination. All other patients showed constant good to excellent clinical and radiological findings with high patient satisfaction. DISCUSSION: The use of titanium fulfils the highest demands of biocompatibility while at the same time allowing the possibility of an oncological examination using suitable turbo-spinecho-sequences in MRI.

Adolescent↗

The biological response to titanium and titanium-aluminium-vanadium alloy particles. II. Long-term animal studies.

The long-term tissue reactions to particulate titanium and titanium-aluminium-vanadium alloy were investigated by the intra-articular injection of material into the knee joints of mice. The tissue response was studied over a period of 2 to 52 weeks. In general, both materials were well tolerated, there was no evidence of necrosis and only a slight thickening of the synovium occurred around particles. Multinucleated giant cells were only rarely seen and no palpable tumours formed in any animal at any site.

Alloys↗

Interaction between hydrogen peroxide and titanium: a possible role in the biocompatibility of titanium.

Hydroxyl radicals formed from hydrogen peroxide during an inflammatory response are potent agents for cellular deterioration. The behaviour of implanted material in terms of its ability to sustain or stop free radical formation may be therefore very important. In vitro studies of titanium which is known to be biocompatible and osseointegrates into human bone were carried out. In our model studies, the production of free radicals from H2O2 at Ti and TiO2 surfaces was measured by spin trapping techniques. Our findings suggest that there is no sustained hydroxyl radical production at a titanium (oxide) surface. We propose that this is due to the quenching of the Fenton reaction through both trapping and oxidation of superoxide radicals in a TiOOH adduct.

Biocompatible Materials↗

Cell damage in vitro following direct contact with fine particles of titanium, titanium alloy and cobalt-chrome-molybdenum alloy.

Fibroblastic cells in vitro were exposed to powders of titanium, titanium-aluminium-vanadium alloy and cobalt-chrome-molybdenum (Co-Cr-Mo) alloy, either in direct contact with the cells or separated from the cells by a microporous membrane. Fine particles of all the materials reduced cell growth when in direct contact with cells, but only the finest particles of Co-Cr-Mo alloy caused cell damage through the microporous membrane. This provides further evidence that there is a mechanism of cell damage in vitro which depends on a direct interaction between cells and particles and is largely independent of the chemical nature of the particle.

Alloys↗

Titanium lines: a manifestation of metallosis and tissue response to titanium alloy megaprostheses at the knee.

Titanium alloy, in its Ti-318 (Ti-A16-V4) format, is a widely used material for orthopaedic implants. However, it has frequently been reported as causing black staining of the periprosthetic tissues as a result of debris from metallic wear. This process of metallosis has been implicated in implant failure. We report three cases in which titanium alloy prostheses for primary bone tumours at the knee have caused the formation of fluid-filled cysts containing metallic debris. The cysts result in radiological appearances which may mimic soft tissue tumour recurrence and also contribute to post-operative failure of the extensor mechanism of the knee.

Adult↗

Response of MG63 osteoblast-like cells to titanium and titanium alloy is dependent on surface roughness and composition.

The success of an implant is determined by its integration into the tissue surrounding the biomaterial. Surface roughness and composition are considered to influence the properties of adherent cells. The aim of this study was to determine the effect of chemical composition and surface roughness of commercially pure titanium (Ti) and Ti-6A1-4V alloy (Ti-A) on MG63 osteoblast-like cells. Unalloyed and alloyed Ti disks were machined and either fine-polished or wet-ground, resulting in smooth (S) and rough (R) finishes, respectively. Standard tissue culture plastic was used as a control. Surface topography and profile were evaluated by cold field emission scanning electron microscopy and profilometry, while chemical composition was determined using Auger electron spectroscopy and Fourier transform infrared spectroscopy. The effect on the cells was evaluated 24 h postconfluence by measuring cell number, [3H]-thymidine incorporation into DNA, cell and cell layer alkaline phosphatase specific activity (ALPase), osteocalcin and collagen production, [35S]-sulfate incorporation into proteoglycan, and prostaglandin E2 (PGE2) and transforming growth factor-beta (TGF-beta) production. When compared to plastic, the number of cells was reduced on the pure Ti surfaces, while it was equivalent on the Ti-A surfaces; [3H]-thymidine incorporation was reduced on all surfaces. The stimulatory effect of surface roughness on ALPase in isolated cells and the cell layer was more pronounced on the rougher surfaces, with enzyme activity on Ti-R being greater than on Ti-A-R. Osteocalcin production was increased only on the Ti-R surface. Collagen production was decreased on Ti surfaces except Ti-R; [35S]-sulfate incorporation was reduced on all surfaces. Surface roughness affected local factor production (TGF-beta, PGE2). The stimulatory effect of the rougher surfaces on PGE2 and TGF-beta was greater on Ti than Ti-A. In summary, cell proliferation, differentiation, protein synthesis and local factor production were affected by surface roughness and composition. Enhanced differentiation of cells grown on rough vs. smooth surfaces for both Ti and Ti-A surfaces was indicated by decreased proliferation and increased ALPase and osteocalcin production. Local factor production was also enhanced on rough surfaces, supporting the contention that these cells are more differentiated. Surface composition also played a role in cell differentiation, since cells cultured on Ti-R surfaces produced more ALPase than those cultured on Ti-A-R. While it is still unknown which material properties induce which cellular responses, this study suggests that surface roughness and composition may play a major role and that the best design for an orthopaedic implant is a pure titanium surface with a rough microtopography.

Alkaline Phosphatase↗

Quantitative risk assessment for accidental release of titanium tetrachloride in a titanium sponge production plant.

This paper outlines the quantitative risk assessment for storage and purification section of a titanium sponge production facility. Based on qualitative HAZAN technique, which involves a detailed FETI and HAZOP study of the entire plant, the storage and the purification section were found to be the most hazardous sections. Titanium tetrachloride (TiCl(4)) is the major reactant used in this plant. TiCl(4) is a toxic, corrosive water reactive chemical and on spillage from containment creates a liquid pool that can either boil or evaporate leading to the evolution of toxic hydrogen chloride (HCl). Fault tree analysis technique has been used to identify the basic events responsible for the top event occurrence and calculate their probabilities. Consequence analysis of the probable scenarios has been carried out and the risk has been estimated in terms of fatality and injuries. These results form the basic inputs for the risk management decisions.

Accidents, Occupational↗

Mononuclear titanium(IV)-citrate complexes from aqueous solutions: pH-specific synthesis and structural and spectroscopic studies in relevance to aqueous titanium(IV)-citrate speciation.

Titanium is a metal frequently employed in a plethora of materials supporting medical applications. In an effort to comprehend the involvement of titanium in requisite biological interactions with physiological ligands, synthetic efforts were launched targeting aqueous soluble species of Ti(IV). To this end, aqueous reactions of TiCl(4) with citric acid afforded expediently, under pH-specific conditions, the colorless crystalline materials Na(6)[Ti(C(6)H(4.5)O(7))(2)(C(6)H(5)O(7))].16H(2)O (1) and Na(3)(NH(4))(3)[Ti(C(6)H(4.5)O(7))(2)(C(6)H(5)O(7))].9H(2)O (2). Complexes 1 and 2 were characterized by elemental analysis, FT-IR, (13)C-MAS solid state and solution NMR, cyclic voltammetry, and X-ray crystallography. 1 crystallizes in the triclinic space group P, with a = 15.511(9) A, b = 15.58(1) A, c = 9.848(5) A, alpha = 85.35(2) degrees, beta = 76.53(2) degrees, gamma = 61.97(2) degrees, V = 2042(2) A(3), and Z = 2. 2 crystallizes in the triclinic space group P, with a = 12.437(5) A, b = 12.440(5) A, c = 12.041(5) A, alpha = 83.08(2) degrees, beta = 81.43(2) degrees, gamma = 67.45(2) degrees, V = 1697(2) A(3), and Z = 2. The X-ray structures of 1 and 2 reveal the presence of a mononuclear complex, with Ti(IV) coordinated to three citrate ligands in a distorted octahedral geometry around Ti(IV). The citrates employ their central alkoxide and carboxylate groups to bind Ti(V), while the terminal carboxylates stay away from the Ti(IV)O(6) core. Worth noting in 1 and 2 is the similar mode of coordination but variable degree of protonation of the bound citrates, with the locus of (de)protonation being the noncoordinating terminal carboxylates. As a result, this work suggests the presence of a number of different Ti(IV)-citrate species of the same nuclearity and coordination geometry as a function of pH. This is consistent with the so far existing pool of mononuclear Ti(IV)-citrate species and provides a logical account of the aqueous speciation in the requisite binary system. Such information is vital in trying to delineate the interactions of soluble and bioavailable Ti(IV) forms promoting biological interactions in humans. To this end, chemical properties, structural attributes, and speciation links to potential ensuing biological effects are dwelled on.

Biological Availability↗

Molybdenum and copper catalysis of reductions by titanium(II) and titanium(III).

Reductions of vanadium(IV), benzoquinone, and tri-iodide, both by titanium(III) and by titanium(II), are catalyzed by molybdenum(VI). The VO(2+)-Ti(II) reaction is catalyzed by copper(II) as well. Reactions of Ti(II) with the oxidant in excess yield Ti(IV), as do reductions by Ti(III). Reactions proceed via competing uncatalyzed and catalyzed paths, with the latter components first order in catalyst. Kinetic patterns indicate that monomeric Mo(v) is the active species, but the dimeric Mo(v) species, [Mo(2)O(4)](2+), is without catalytic action. Catalytic constants pertaining to Ti(III) are remarkably similar to those for Ti(II), despite the 0.47 V difference in the standard potentials of the two reductants.

Benzoquinones↗

Acute biological effects of intratracheally instilled titanium dioxide whiskers compared with nonfibrous titanium dioxide and amosite in rats.

The dimensions of man-made mineral fiber whiskers are similar to those of some kinds of asbestos. Thus these mineral fibers raise the concern for potential health hazard for workers exposed in the occupational environments. This study was designed to define acute biological effects of intratracheally administered titanium dioxide whiskers (TO1) compared with nonfibrous titanium dioxide (TOP) and UICC amosite (Ams), and their relations to acute lung inflammation in rats. The observed geometric mean length (microm) and width (microm) and geometric standard deviation are: TO1(2.1[2.0], 0.14[1. 53]); Ams (4.3[3.3], 0.31[1.9]); and TOP (50 nm, 1-2 microm aggregates). Ten-week-old Wistar-Jcl male rats received a single tracheal injection of test materials at doses between 0.05 and 1.0 mg/rat. Control animals were injected with the same volume of saline. Lung tissue and bronchoalveolar lavage (BAL) fluid were collected from rats on days 1, 3, and 7 after administration. In the group injected with TO1, total protein, cytokine-induced neutrophil chemoattractant (CINC)/growth-regulated gene product (GRO), interleukin (IL) 1beta, and tumor necrosis factor (TNF) alpha increased on day 1. Subsequently, total elastolytic activity and fucose levels in BAL increased by day 3. All parameters, except for fucose in BAL, recovered to the normal levels. Animals in the Ams group showed increased total protein and CINC/GRO and decreased total elastolytic activity in a dose-dependent manner on day 1. The fucose level increased on day 3 in the Ams group. All parameters returned to their control levels on day 7. Animals in the TOP group did not show significant changes any of parameters during the experimental period. Gene expression of TNF-alpha and monocyte chemoattractant protein (MCP) 3 in the lung increased dose-dependently in the animals treated with the three materials. The mRNAs for eotaxin and MIP-1alpha were overexpressed in the lung of animals treated with Ams and TO1, while RANTES mRNA was overexpressed dose-dependently in the lung of animals treated with Ams on day 1. Onset of inflammatory response was more rapid in the Ams group than the TO1 group. Recovery of the fucose level in BAL was slower in the TO1 group than in the Ams group, though we observed similar histopathological changes in the lung of animals with TO1 or Ams. We conclude that whisker-induced acute biological effects in the lung may be related to the shape of the whiskers and not to their chemical composition or surface crystal structure, showing biological effects similar to those of UICC amosite.

Administration, Inhalation↗

Comparing apical preparations of root canals shaped by nickel-titanium rotary instruments and nickel-titanium hand instruments.

This study measured displacement of canal centers in extracted human teeth after preparation by Lightspeed and nickel-titanium K-files. The specimens were divided into two groups (n = 11), after radiographing the roots from the buccolingual and mesiodistal planes with pathfinding files in situ. More strongly and less strongly curved canals were, respectively, assigned to the Lightspeed and nickel-titanium K-file groups. Using a reassembly technique, cross-sections at 1.25 mm, 3.25 mm, and 5.25 mm from the apices were made of the experimental roots embedded in clear plastic. Stereomicroscopic 35-mm slides were taken of the uninstrumented sectioned canals. The sections were reassembled and then prepared to size 50 Master Apical Rotary and size 40 Master Apical Files, for the Lightspeed and K-file groups, respectively. Similar 35-mm slides of the instrumented canals were taken and electronically superimposed over their uninstrumented counterparts. Displacements of root canal centers after preparation and increases in cross-sectional areas of the prepared root canals were evaluated at specific levels. No significant differences in displacement of canal centers or between the mean cross-sectional areas of the instrumented root canals were recorded between the Lightspeed and K-file groups. Both types of instruments produced similar displacement of canal centers after preparation.

Anatomy, Cross-Sectional↗

Reliability of cranial flap fixation techniques: comparative experimental evaluation of suturing, titanium miniplates, and a new rivet-like titanium clamp (CranioFix): technical note.

OBJECTIVE: To ensure patients' safety, the mechanical strength of cranial flap refixation techniques and implants (sutures, titanium miniplates, and new rivet-like titanium clamps) had to be validated. METHODS: With craniotomied cadaver skulls for each refixation technique, load-bearing tests were performed by applying an external force until an impression depth of the cranial flap of 2 mm was reached and the results were compared. RESULTS: CranioFix (Aesculap AG, Tuttlingen, Germany) and miniplates were revealed to be the strongest fixation devices, although with miniplates, the plastic deformation started from the beginning of load application, whereas CranioFix additionally provided a better spring-elastic reserve and a higher reproducibility of fixation strength not dependent on bone thickness and consistency. Flaps fixed by sutures were dislocated from the start. CONCLUSION: Although CranioFix offers distinct advantages over miniplates, both proved to be definitely superior to suturing, which is still used in many centers. Therefore, whether suturing can still be regarded as a state-of-the-art technique must be reconsidered.

Bone Plates↗

Anterior surgery with insertion of titanium mesh cage and posterior instrumented fusion performed sequentially on the same day under one anesthesia for septic spondylitis of thoracolumbar spine: is the use of titanium mesh cages safe?

STUDY DESIGN: Retrospective study. OBJECTIVE: To evaluate the outcome on patients with pyogenic spondylitis of the thoracolumbar spine following combined anterior and posterior surgery. SUMMARY AND BACKGROUND DATA: Several methods of surgical treatment of pyogenic spondylitis have been reported. These include anterior approach, staged and simultaneous anterior decompression, and posterior stabilization. The use of anterior implants in the presence of an infection presents a challenge for spine surgeons. This study analyzes the clinical and radiologic outcome of surgical intervention on patients with pyogenic spondylitis of the thoracolumbar spine who were treated surgically for intractable pain, instability, and neurologic impairment. METHODS: Fourteen patients (6 women, 8 men) with thoracolumbar spondylitis were treated with anterior surgery with insertion of titanium mesh cage and posterior instrumented fusion performed sequentially on the same day under one anesthesia. The age (average, SD) of the patients at the time of surgery was 55 +/- 16 years (range, 29-83 years). Most patients had also systemic diseases as lung tuberculosis, hepatic cirrhosis, diabetes mellitus, or chronic renal failure. Patients were evaluated before and after surgery in terms of pain, neurologic level, sagittal spinal balance, and radiologic fusion. RESULTS: The average duration of the combined surgery was 4.5 hours. All patients were observed up for an average of 45 months (range, 37-116 months). The Visual Analog Scale score (average, range) improved from 7 (range, 4-10) before surgery to 2 (range, 0-5) after surgery. Correction (average, range) of segmental kyphotic deformity was 6 degrees (range, 0 degrees-11 degrees) without loss of correction at the final observation. Neither a postoperative change of the position of mesh cage nor any posterior instrumentation failure was recorded. Patients with incomplete neurologic impairment showed improvement after surgery at an average 1.4 Frankel's grade. There was one complication, an anterior wound abscess culminating in an abdominal hernia. CONCLUSIONS: This clinical study showed that patients with thoracolumbar osteomyelitis can successfully undergo anterior surgery with insertion of titanium mesh cage and posterior instrumented fusion performed sequentially on the same day under one anesthesia. The presence of the mesh cage anteriorly at the site of spondylitis had no negative influence on the course of infection healing, and additionally it stabilized the affected segment maintaining sufficient sagittal profile.

Adult↗

Oxidized titanium implants (Nobel Biocare TiUnite) compared with turned titanium implants (Nobel Biocare mark III) with respect to implant failure in a group of consecutive patients treated with early functional loading and two-stage protocol.

OBJECTIVES: The purpose of this study was to compare two implant types of similar shape but with different surfaces with respect to implant failure. MATERIAL AND METHODS: A total of 136 patients were treated with Nobel Biocare Implants between January 2001 and December 2002. Totally 394 implants were placed, of which 199 were oxidized titanium implants (Nobel Biocare TiUnite and 195 with turned titanium surface (Nobel Biocare Mark III. Sixty-three patients underwent a one-stage surgical protocol, of which 24 were objected to early functional loading. The remaining 73 patients were treated with a traditional two-stage surgical protocol. All patients were followed for a minimum of 5 months after loading of the implants. Implants were classified as survivals when clinically stable and fulfilling purported function without any discomfort to the patient, with no signs of infection or ongoing pathologic process. RESULTS: Seven implants were lost in five patients (two males and three females), six in the maxilla and one in the mandible. All failed implants were Mark III implants, inserted following the traditional two-stage protocol. The implant success rate was 98.2% for the whole-patient group, divided as a 100% success rate following the implants with oxidized surface (Nobel Biocare TiUnite compared with a success rate of 96.4% with implants with turned surface (Nobel Biocare Mark III).

Adult↗

Microvascular changes after placement of titanium implants: scanning electron microscopy observations of machined and titanium plasma-sprayed implants in dogs.

BACKGROUND: The purpose of this study was to clarify the osseointegration process of titanium implants through study of the vascular architecture and bone apposition. The smooth machined-surface implant is tightly fixed to the bone by its threads. The rough titanium plasma-sprayed (TPS) coated implants give a scaffold for new bone. METHODS: Twelve beagle dogs were used, and 2 surface types of implants were inserted in the mandible. Vascular injection was given 14, 30, and 120 days after surgery. The soft tissue was digested by proteinase solution, and specimens were examined by scanning electron microscope (SEM). RESULTS: Fourteen days after placement of machined implants, new vessels could be seen branching out from the vascular network of the bone marrow. In TPS implants, a vascular network was seen between the bone-implant interface. At 30 days, the vessels were arranged in a groove corresponding to the machined fixture. With TPS implants, new bone was visible along the surface of the fixture, and the vascular network was buried in the bone. At 120 days after placement of machined implants, bone had formed a smooth surface. A few blood vessels were arranged along the bone surface. With TPS implants, a rough bone surface and flat vessels were observed on its surface. CONCLUSIONS: Implants become osseointegrated in different ways, depending on their structures and the characteristics of their surfaces. From the microcirculation point of view, the vessels are an important factor for the remodeling of bone.

Alveolar Process↗

Tissue response to titanium implants in the rat maxilla: ultrastructural and histochemical observations of the bone-titanium interface.

BACKGROUND: The detailed mechanism of osseointegration, the most appropriate implant-bone interface, remains unclear in jaw tissues at the ultrastructural level in contrast to the many reports using long bones. The present study reports on tissue response to titanium-implantation on an animal model using rat maxilla. METHODS: Animals were sacrificed at 1 to 28 days post-implantation and prepared tissue specimens, freed from implants by a cryofracture technique, were processed for transmission electron microscopy and histochemistry for tartrate resistant acid phosphatase activity (TRAPase). RESULTS: Different patterns in bone formation were recognized between lateral and base areas of implant cavities. In the lateral area with narrow gaps, bone deposition took place from the pre-existing bone towards the implant after active bone resorption by osteoclasts reactive to TRAPase. However, no distinct bone formation appeared in the lateral area where the implant had been installed close to the osteotomy margin. On the other hand, new bone formation was found at the base area without any apparent bone resorption. Interestingly, mononuclear cells reactive to TRAPase, presumably preosteoclasts, frequently occurred near preosteoblasts. Osseointegration around the implants was obtained in this model by 28 days post-implantation except for the lateral area with complete contact with implants, where the thin layer remained in contact with the implant surface. CONCLUSIONS: These findings indicate that ossification proceeds at different modes around the titanium implant in rat maxilla, depending on the nature of the recipient bones and the dimension of the gap between the implant and osteotomy margin.

Animals↗

Myelointegration of titanium implants: B lymphopoiesis and hemopoietic cell proliferation in mouse bone marrow exposed to titanium implants.

Multinucleated giant cells have been observed at interfaces between bone marrow and titanium implants in mouse femurs. This raises concern that macrophage-derived factors might perturb local lymphohemopoiesis, possibly even predisposing to neoplasia in the B lymphocyte lineage. It has been found that an implant-marrow interface with associated giant cells persists for at least 1.5 years. Precursor B cells show early increases in number and proliferative activity. At later intervals, however, they do not differ significantly from controls, and there are no perturbations in spatial localization of either B lineage cells or DNA-synthesizing hemopoietic cells. The results of this investigation in mice demonstrate that, following initial marrow regeneration and fluctuating precursor B cell activity, and despite the presence of giant cells, titanium implants apparently become well-tolerated by directly apposed bone marrow cells in a lasting state of "myelointegration."

Analysis of Variance↗