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New reconstructive technologies in skull base surgery: role of titanium mesh and porous polyethylene.

OBJECTIVE: To report on 8 years of experience with 156 titanium mesh and porous polyethylene implants used for craniofacial reconstruction after skull base surgery in 100 patients. DESIGN: Cohort study with a mean follow-up of 5 years. SETTING: Population based. PATIENTS: A consecutive sample of 100 patients treated for skull base tumors or craniofacial trauma who underwent reconstruction with 156 3-dimensional titanium mesh and/or porous polyethylene implants. A retrospective review of the Skull Base Program database, along with photographic and imaging documentation, was undertaken. MAIN OUTCOME MEASURES: Rate of complications as well as the degree of functional and esthetic reconstruction. INTERVENTION: The reconstructive technique focused primarily on the substitution of removed craniofacial skeleton for oncologic reasons or soft tissue defects. RESULTS: After completion of follow-up (mean, 5 years), all 100 patients remained healed except for 7 patients (7%) with 8 implants (5%). Overall, excellent craniofacial symmetry and stability were achieved with both types of implants. CONCLUSIONS: Immediate craniofacial skeletal reconstruction and soft tissue augmentation is feasible with 3-dimensional titanium mesh and porous polyethylene implants. The reviewed 8-year evolution in the use of these technologies (156 implants in 100 patients) highlights the excellent tolerance of these implants (5% implant complication rate) in 100 patients (7% complication rate). The few encountered complications were judged to be primarily related to the quality of the overlying soft tissue and not to the implants themselves. The advantages of using these implants for immediate 3-dimensional skeletal and soft tissue substitution, including availability, easy contouring, stability, primary healing, and tolerance of adjuvant therapy, translate to an improved function and esthetic appearance, with a better quality of life for patients.

Adolescent↗

Preliminary clinical experience with the titanium Greenfield vena caval filter.

Preliminary clinical experience in 40 patients from three institutions is reported for a new titanium model of the Greenfield vena caval filter. The titanium filter is slightly larger than the standard stainless steel filter and can be loaded into a 12 F diameter carrier system as opposed to the 24 F stainless steel filter. In patients ranging from 17 to 94 years of age, percutaneous insertions were made from the right femoral vein in 24 patients, the left femoral vein in 11 patients, and the right internal jugular in 2 patients. Operative access was obtained in 1 patient each from the right femoral, right jugular, and a lumbar vein at laparotomy. Insertion was completed in all cases but 1 and only 1 patient (3%) showed postoperative femoral vein thrombosis. Distal filter migration was seen in 3 cases (7.5%) without sequelae, and there was no proximal migration. The titanium Greenfield vena caval filter provides improved ease of insertion, and the sheath technique should prevent misplacement. Distal migration should be preventable by techniques to promote hook engagement at the time of insertion.

Adolescent↗

Bone-bonding behavior of plasma-sprayed coatings of BioglassR, AW-glass ceramic, and tricalcium phosphate on titanium alloy.

The bone-bonding behavior of three kinds of bioactive ceramics coated on titanium alloy by the plasma-spray technique was investigated. Titanium alloy (Ti-6A1-4V) coated with BioglassR (45S5), apatite-wollastonite containing glass ceramic (AW), or beta-tricalcium phosphate (TCP) was prepared, and rectangular specimens were implanted into the tibial bones of mature male rabbits, which were sacrificed 8 or 24 weeks after implantation. The tibiae containing the implants were dissected out and subjected to detachment tests to measure the failure load. The bone-implant interface was investigated by Giemsa surface staining, contact microradiography, and scanning electron microscopy-electron probe microanalysis (SEM-EPMA). Eight weeks after implantation, the failure loads for implants coated with BioglassR, AW, and TCP were 1.04 +/- 0.94, 2.03 +/- 1.17, and 3.91 +/- 1.51 kg, respectively, and 24 weeks after implantation, the respective failure loads were 2.72 +/- 1.33, 2.39 +/- 1.30, and 4.23 +/- 1.34 kg. Failure loads of AW- and TCP-coated implants did not increase significantly with time. After the detachment test, breakage of the coating layer was observed. Bioactive ceramics can act as stimulants that induce bonding between bone and metal implants. However, failure load of metal implants coated with the bioactive ceramics was lower than that of bulk AW or TCP. It appears impossible to obtain a higher failure load using a bioactive-ceramic coating on titanium alloy. Histologically, the coating layer was found to become detached from the metal implant and the bone tissue bonded to the coating layer. SEM-EPMA observation revealed breakage of the coating layer, although bonding between bone and the coating layer was evident. A Ca-P-rich layer was observed at the interface between bone and the AW coating, and a Ca-P-rich and a Si-rich layer were observed at the interface between bone and the BioglassR coating. For clinical application, it would seem better to use coated metal implants for short-term implantation. However, there is a possibility of breakage of the coating layer because of both dissolution of the bioactive ceramic and mechanical weakness at the interface between the coating layer and the metal implant.

Alloys↗

Types I and III collagen in the tissue capsules of titanium and stainless-steel implants.

Collagen plays an important role in wound healing and as such is present in connective tissue capsules around implanted materials. The proportion of type I collagen to type III collagen is lower during wound healing than that found in normal dermis, but the amount of type I collagen gradually increases and type III decreases as healing continues. The intent of this research was to investigate a possible correlation between implant metals and type I and type III collagen formation in the ensuing soft-tissue capsules. Smooth implants of grade 4 commercially pure titanium and 316L stainless steel were placed via injection needle into the subcutaneous tissue of 12 rats for 6 weeks. The soft-tissue capsule that formed around each implant was evaluated histologically and by immunofluorescence. Although the two metal implant types differ in many respects, they were chosen for their differences in surface conductivity. Titanium oxide is semiconducting, whereas the oxide of stainless steel is conducting. Impedance spectroscopy was used for conductivity analysis of the surface. No qualitative differences were found in amount of type I or type III collagen in the capsules of the two metals. However, the capsules around titanium stained for type I collagen were thicker than capsules around stainless steel. In addition, type I collagen showed evidence of a greater association with densely packed, highly orientated collagen fibers.

Animals↗

Bioactivity of titanium treated with hydrogen peroxide solutions containing metal chlorides.

Commercially available pure metallic titanium was chemically treated at 60 degrees C for 24 h with H2O2 solutions containing various metal chlorides to provide titanium with bioactivity, that is, to give it the ability to form a biologically active bone-like apatite layer on the surface. After the chemical treatment the titanium specimens were soaked in a simulated body fluid (the Kokubo solution). Apatite was found to deposit on the specimens treated with the H2O2/TaCl5 and H2O2/SnCl2 solutions. X-ray photoelectron spectroscopic (XPS) study of the specimens treated with those H2O2 solutions indicated that basic Ti-OH groups in titania hydrogel layers on their surfaces were responsible for apatite nucleation and growth.

Body Fluids↗

Biocompatibility of nickel-titanium shape memory metal and its corrosion behavior in human cell cultures.

Nickel-titanium alloy (Nitinol) is a metallic biomaterial that has a unique thermal shape memory, superelasticity, and high damping properties. Nitinol is potentially very useful in orthopedic surgery, for example. At present, there are not enough confirmative biocompatibility data available on Nitinol. The aim of our study was to clarify the primary cytotoxicity and corrosion rate of Nitinol in human cell cultures. Comparisons were made with stainless steel (Stst), titanium (Ti), composite material (C), and control cultures with no test discs. Human osteoblasts (OB) and fibroblasts (FB) were incubated for 10 days with test discs of equal size, 6 x 7 mm. The cultures were photographed and the cells counted. Samples from culture media were collected on days 2, 4, 6, and 8, and the analysis of metals in the media was done using flameless atomic absorption spectrophotometry. The proliferation of FB was 108% (Nitinol), 134% (Ti) (p < 0.02), 107% (Stst), and 48% (C)(p < 0.0001) compared to the control cultures. The proliferation of OB was 101% (Nitinol), 100% (Ti), 105% (Stst), and 54% (C) (p < 0.025) compared to the controls. Initially, Nitinol released more nickel (129-87 micrograms/L) into the cell culture media than Stst (7 micrograms/L), but after 2 days the concentrations were about equal (23-5 micrograms/L versus 11-1 micrograms/L). The titanium concentrations from both Nitinol and Ti samples were all < 20 micrograms/L. We conclude that Nitinol has good in vitro biocompatibility with human osteoblasts and fibroblasts. Despite the higher initial nickel dissolution, Nitinol induced no toxic effects, decrease in cell proliferation, or inhibition on the growth of cells in contact with the metal surface.

Biocompatible Materials↗

Effects of titanium substratum and grooved surface topography on metalloproteinase-2 expression in human fibroblasts.

The chemical and topographic effects of commercially pure titanium on cell morphology and the regulation of matrix metalloproteinase-2 (MMP-2) gene expression, synthesis, and activity were investigated in early passage human gingival fibroblasts. Scanning electron microscopy showed that on smooth titanium (Ti), fibroblasts remained well spread and randomly oriented throughout the culture period. In contrast, cells on V-shaped grooved titanium (VTi) were oriented along the grooves by 16 h and proliferated in this organization throughout the culture period. The effects of substratum surface chemistry on MMP-2 expression were found to be distinct from those of topography. Northern hybridization analysis of fibroblasts cultured on Ti revealed an MMP-2 mRNA time-course expression pattern parallel to that observed on the tissue culture plastic (TCP) dishes, but at significantly lower levels at each time-point. The Ti mRNA levels were decreased by 34% at 16 h, 55% at 40 h, and 45% at 90 h relative to TCP. In contrast, MMP-2 mRNA expression on VTi showed both an altered time-course expression pattern and altered levels compared to Ti and TCP. Relative to TCP, VTi MMP-2 mRNA levels were approximately 80% less at 16 h and approximately 50% less at 40 h, but not significantly different at 90 h. Relative to Ti, VTi MMP-2 mRNA levels were approximately 75% less at 16 h, but approximately 40% greater at 40 h and approximately 70% greater at 90 h. These differences may be explained in part by the observed changes in MMP-2 mRNA half-life which decreased by approximately 40% on Ti but increased by over fourfold on VTi relative to TCP. The smooth Ti also showed an approximate twofold increase of MMP-2 secretion in the late cultures over TCP controls. These results indicate that substratum surface chemistry and topography-induced changes in cell shape can alter MMP-2 expression in normal fibroblasts. The molecular approach to investigating the major molecules involved in tissue degradation may provide sensitive indicators of tissue remodeling at the tissue-biomaterial interface.

Biocompatible Materials↗

The effect on immunocytes of anodic oxide titanium after hydrothermal treatment.

All dental root implants come in contact with the oral epithelium, and many complex factors are found to arise in this region. In order to perform a successful dental root implantation, it is necessary to clarify the interaction of the dental root implant material with the host defense mechanisms involved in the specific and nonspecific immune responses to many antigens in oral bacteria and their components. Recently, focusing on developing the dental root implant, the Nikon Corporation improved the surface characteristics of pure titanium even further by developing a hydroxyapatite (HA) layer formed on an anodic titanium oxide film containing Ca and P via hydrothermal treatment (SA treatment). However, since little is known about the effect of SA-treated pure titanium (HA/Ti) on the defense mechanisms of the oral membrane epithelium, we investigated (1) the in vitro proliferation of murine splenic B lymphocytes on the surface of HA/Ti in the presence of three lipopolysaccharide (LPS) concentrations and (2) interleukin-1alpha (IL-1alpha) production by the reaction of human peripheral blood mononuclear cells (PBM cells) on the surface of HA/Ti under the same concentrations. After culture, murine splenic lymphocytes were measured by uptake of 3H-thymidine, and cytokine release (IL-1alpha) from PBM cells was measured by ELISA. Results showed that HA/Ti had hardly any effect on the LPS-induced proliferation of B lymphocytes and IL-1alpha production. In vitro investigations of the effects of HA/Ti on the LPS-induced proliferation of murine splenic B lymphocytes and IL-1alpha from PBM cells might be a useful way of elucidating the defense mechanism between implants and the oral epithelium.

Animals↗

Analysis of titanium dental implants after failure of osseointegration: combined histological, electron microscopy, and X-ray photoelectron spectroscopy approach.

A multitechnique approach has been used to characterize the surface of nonosseointegrated titanium implants and the surrounding biological tissues. Five pure titanium dental implants were used as reference, and 25 removed implants were studied. Surface and in-depth chemical compositions of the implants (from a total of 16 patients) were investigated by X-ray photoelectron spectroscopy (XPS). Histological slides of the surrounding tissues were examined by light microscopy, XPS, and electron microprobe analysis. None of the failed implants presented the regular surface composition and depth profile of the TiO2 overlayer; foreign elements (Ca, Na, P, Si, Cl, Zn, Pb, and Al) were observed on some implants. Fibrosis, lymphocytic and plasmocytic infiltrates, and granulomatous lesions were detected in the surrounding tissues. XPS and electron microprobe analysis indicated the presence of Zn, Fe, Sn, and Ti in the tissues. As a possible scenario for implant failure, we propose and discuss a oxidoreduction mechanism, leading to a partial dissolution or the complete dissociation of the protective titanium dioxide overlayer and to ion diffusion through the surrounding tissues.

Connective Tissue↗

Graded surface structure of bioactive titanium prepared by chemical treatment.

An NaOH treatment of pure titanium (Ti) forms a sodium titanate hydrogel surface layer with a smooth graded interface structure to the Ti metal substrate. Subsequent heat treatment at 600 degrees C of the NaOH-treated Ti forms an amorphous sodium titanate surface layer with a smooth graded interface structure similar to the Ti metal substrate. These treated Ti metals both form an apatite surface layer with a smooth graded interface structure to the Ti metal substrates in simulated body fluid (SBF). The smooth graded interface structures give a tight bond of the apatite layer to the substrates. Heat treatment at 800 degrees C of the NaOH-treated Ti forms crystalline sodium titanate and a rutile surface layer with a graded interface structure to the Ti metal substrate, which is intervened by a thick titanium oxide. This substrate forms an apatite layer with a graded interface structure to the Ti metal substrate, which is intervened by a thick titanium oxide in SBF. This irregular graded structure gives a less tight bond of the apatite layer to the substrate.

Apatites↗

The cytotoxic effect of titanium particles phagocytosed by osteoblasts.

The cytotoxic effect of different concentrations of titanium particles on osteoblasts was studied in vitro. It was found that the viability of the osteoblasts was inversely proportional to the particle concentration. Phagocytosis of particles by the osteoblasts was evident and was demonstrated to be responsible for cell necrosis. Moreover, during and after phagocytosis, the osteoblasts released products that were cytotoxic for other osteoblasts, as established with a conditioned medium assay. The titanium particles thus had both a direct and an indirect effect on osteoblast viability. It also was observed that the titanium particles induced a process of programmed cell death (apoptosis) when co-cultured with osteoblasts. The results of this study suggest that not only is the amount of wear debris generated important, but the local accumulation of the debris also may have a significant impact on bone cell function.

Analysis of Variance↗

Titanium substrata composition influences osteoblastic phenotype: In vitro study.

In spite of observed differences at the interface between boon and either commercially pure titanium [Ti(cpi)] or titanium alloy (Ti-6Al-4V), the mechanism of such a response is ill understood. This prompted further investigation of the influence of similar metals on human bone-derived cells (HBDCs). This study investigated the influence of Ti(cpi) and its alloy on osteoblastic proteins formed by HBDCs grown for 5, 7, 10, and 14 days on these metals and compared them to cells grown on tissue culture polystyrene plates. Messenger RNA and translated proteins that form an array of osteogenic parameters were determined: alkaline phosphatase (ALP), thrombospondin, osteopontin, osteocalcin (OC), osteonectin (ON/SPARC), type I collagen (Col I) and bone sialoprotein (BSP). At the four predetermined time points, cells grown on either Ti(cpi) or Ti-6Al-4V generally expressed similar mRNA levels, while levels of their respective proteins differed. Cells on Ti(cpi) had peak levels for most proteins at day 7, whereas those on Ti-6Al-4V peaked at either day 5 and/or day 7. At day 5 cells grown on Ti-6Al-4V had higher levels of ALP, Col I, ON/SPARC, OC, and BSP than those in Ti(cpi); this difference was not maintained at later time points in culture. The differential regulation of proteins occurring between cells from the same patient grown on titanium and its alloy implies that HBDCs respond to small differences in the surface chemistry and/or microcrystallinity.

Adolescent↗

Striated muscle microvascular response to silver implants: A comparative in vivo study with titanium and stainless steel.

Local microvascular perfusion is the primary line of defense of tissue against microorganisms and plays a considerable role in reparative processes. The impairment of the microcirculation by a biomaterial may therefore have profound consequences. Silver is known to have excellent antimicrobial activity and, although regional and systemic toxic effects have been described, silver is regularly discussed as an implant material in bone surgery. Because little is known about the influence of silver implants on the adjacent host tissue microvasculature, we studied in vivo nutritive perfusion and leukocytic response, and compared these results with those of the conventionally used materials titanium and stainless steel. Using the hamster dorsal skinfold chamber preparation and intravital microscopy, the implantation of a commercially pure silver sample led to a distinct and persistent activation of leukocytes combined with a marked disruption of the microvascular endothelial integrity, massive leukocyte extravasation, and considerable venular dilation. Whereas animals with stainless-steel implants showed a moderate increase in these parameters with a tendency to recuperate, titanium implants caused only a transient increase of leukocyte-endothelial cell interaction within the first 120 min and no significant change in macromolecular leakage, leukocyte extravasation and venular diameter. After 3 days, five of six preparations with silver samples showed severe inflammation and massive edema. Thus, the use of silver as an implant material should be critically judged despite its bactericidal properties. The implant material titanium seems to be well tolerated by the local vascular system and currently represents the golden standard.

Animals↗

Comparison of artifacts produced from carbon fiber and titanium alloy needles at 1.5 T MR imaging.

A novel coaxial carbon fiber-based biopsy needle set was investigated in phantom experiments and compared with a commercially available, magnetic resonance (MR)-compatible titanium alloy set using MR imaging at 1.5 T. Image artifacts observed with different MR sequences were assessed. It was found that the carbon fibers produced distinctly smaller image artifacts compared with the titanium needle. Depending on the type of MR sequence, the relative range of artifact size ratios between the carbon and titanium needles was between 0.7 (spin-echo sequence) and 0.4 (gradient-echo sequence) with the needles oriented perpendicular to the main magnetic field. Carbon fiber composites are promising materials for the design and construction of MR-compatible instruments.

Artifacts↗

An X-ray photoelectron spectroscopy study of the process of apatite formation on bioactive titanium metal.

Bioactive titanium metal, prepared by treatment with NaOH followed by an annealing stage to form a sodium titanate layer with a graded structure on its surface, forms a biologically active bone-like apatite layer on its surface in the body, and bonds to bone through this apatite layer. In this study, process of apatite formation on the bioactive titanium metal in a simulated body fluid was investigated using X-ray photoelectron spectroscopy. The bioactive titanium metal formed Ti-OH groups soon after soaking in the simulated body fluid, via the exchange of the Na(+) ions in the sodium titanate on its surface with H(3)O(+) ions in the fluid. The Ti-OH groups on the metal combined with the calcium ions in the fluid immediately to form a calcium titanate. After a long period, the calcium titanate on the metal took the phosphate ions as well as the calcium ions in the fluid to form the apatite nuclei. The apatite nuclei then proceeded to grow by consuming the calcium and phosphate ions in the fluid. These results indicate that the Ti-OH groups formed on the metal induce the apatite nucleation indirectly, by forming a calcium titanate. The initial formation mechanism of the calcium titanate may be attributable to the electrostatic interaction of the negatively charged Ti-OH groups with the positively charged calcium ions.

Apatites↗

Proteomic analysis of human skin fibroblasts grown on titanium: novel approach to study molecular biocompatibility.

Despite the growing use of titanium as an implant material, there is a lack of consensus on what constitutes the molecular basis of its biocompatibility. In the present study we compared the response of skin fibroblasts to two different growth supporting surfaces: commercially pure titanium (cpTi) and tissue culture polystyrene (TCPS). Proteins from extracts of whole cells and adsorbed serum were separated and identified by 2-dimensional gel electrophoresis. In all, 40 proteins (46 spots) were identified by matrix-assisted laser desorption/ionization and mass spectrometry, database searching, immunoblotting, running a standard, or a combination of these techniques. Many of the proteins collected from the two surfaces were found to derive from the serum used in the culture medium. The surface properties of titanium appeared to promote the formation of a more concentrated carpet of serum proteins. Several proteins from bovine or human serum, such as albumin, alpha2-HS-glycoprotein, alpha-fetoprotein, plasminogen, thrombospondin 1, and serotransferrin, along with a few unidentified serum components, were found to adsorb onto cpTi in comparatively high concentrations. The adsorption of serum proteins did not appear to be selective on either substrate. We found that among the major cellular proteins, fibronectin and a cytoskeletal protein (non-muscle myosin heavy chain type A) were expressed at lower levels by fibroblasts grown on cpTi compared to TCPS. By analyzing the changes in the entire proteome of cells in response to different growth substrates, we may gain a better understanding of the molecular basis of biocompatibility.

Animals↗

Titanium-based molecular squares and rectangles: syntheses by self-assembly reactions of titanocene fragments and aromatic N-heterocycles.

This paper reports on the potential of titanium compounds as building blocks for supramolecular polygons. Self-assembly reactions of low-valent titanocene units and N-heterocyclic bridging ligands lead to novel titanium-based supramolecular squares. Pyrazine (3), 4,4'-bipyridine (4), and tetrazine (5) were used as bridging ligands, and the acetylene complexes [Cp2Ti{eta2-C2(SiMe3)2}] (1) and [(tBuCp)2Ti{eta2-C2(SiMe3)2}] (2) as sources of titanocene fragments. Molecular rectangles can be synthesized by stepwise reduction of the titanocene dichlorides [Cp(2)TiCl2] and [(tBuCp)2TiCl2] and consecutive coordination of two different bridging ligands. The resulting complexes are the first examples of molecular rectangles containing bent metallocene corner units. Single-crystal X-ray analyses of the tetranuclear compounds revealed the geometric properties of the molecular polygons in the solid state. Comparison of bond lengths and angles in coordinated and free ligands reveals the reduced state of the bridging ligand in the low-valent titanium compounds. The syntheses and properties of these novel, highly air- and moisture-sensitive compounds are discussed.

Crystallography, X-Ray↗

Efficient charge injection from the S2 photoexcited state of special-pair mimic porphyrin assemblies anchored on a titanium-modified ITO anode.

A novel surface fabrication methodology has been accomplished, aimed at efficient anodic photocurrent generation by a photoexcited porphyrin on an ITO (indium-tin oxide) electrode. The ITO electrode was submitted to a surface sol-gel process with titanium n-butoxide in order to deposit a titanium monolayer. Subsequently, porphyrins were assembled as monolayers on the titanium-treated ITO surface via phosphonate, isophthalate, and thiolate groups. Slipped-cofacial porphyrin dimers, the so-called artificial special pair at the photoreaction center, were organized through imidazolyl-to-zinc complementary coordination of imidazolylporphyrinatozinc(II) units, which were covalently immobilized by ring-closing olefin metathesis of allyl side chains. The modified surfaces were analyzed by means of X-ray photoelectron spectroscopy. Photoirradiation of the porphyrin dimer generated a large anodic photocurrent in aqueous electrolyte solution containing hydroquinone as an electron sacrificer, due to the small reorganization energy of the dimer. The use of different linker groups led to significant differences in the efficiencies of anodic photocurrent generation. The apparent flat-band potentials evaluated from the photocurrent properties at various pH values and under biased conditions imply that the band structure of the ITO electrode is modified by the anchoring species. The quantum yield for the anodic photocurrent generation by photoexcitation at the Soret band is increased to 15 %, a surprisingly high value without a redox cascade structure on the ITO electrode surface, while excitation at the Q band is not so significant. Extensive exploration of the photocurrent properties has revealed that hot injection of the photoexcited electron from the S2 level into the conduction band of the ITO electrode takes place before internal conversion to the S1* state, through the strong electronic communication of the phosphonyl anchor with the sol-gel-modified ITO surface.

Dimerization↗