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In the field of orthopedics, defects in large bones have proven challenging to resolve. The aim of the present study was to address this problem through the combination of tantalum metal (pTa) with exosomes derived from bone marrow mesenchymal stem cells (BMSCs), which have the potential to enhance regeneration of full thickness femoral bone defects in rats. Cell culture results demonstrated that exosomes improved the proliferation and differentiation of BMSCs. Following establishment of a supracondylar femoral bone defect, exosomes and pTa were implanted into the defect area. Results demonstrated that pTa acts as a core scaffold for cell adhesion and exhibits good biocompatibility. Moreover, micro‑CT scan results as well as histological examination demonstrated that pTa had a significant effect on osteogenesis, with the addition of exosomes further promoting bone tissue regeneration and repair. In conclusion, this novel composite scaffold can effectively promote bone regeneration in large bone defect areas, providing a new approach for the treatment of large bone defects.

To obtain fiber materials with pronounced chemical-biological protection, metal (Zn or Ta) nanoparticles were jointly applied with polyelectrolyte complexes of enzymes and polypeptides being their stabilizers. Computer modeling revealed the preferences between certain polyelectrolyte partners for N -acyl-homoserine lactone acylase and hexahistidine-tagged organophosphorus hydrolase (His 6 -OPH) possessing the quorum quenching (QQ) behavior with bacterial cells. The combinations of metal nanoparticles and enzymes appeared to function better as compared to the combinations of the same QQ-enzymes with antibiotics (polymyxins), making it possible to decrease the applied quantities by orders of magnitude while giving the same effect. The elimination of Gram-positive and Gram-negative bacterial cells from doubly modified fiber materials notably increased (up to 2.9-fold), whereas His 6 -OPH retained its hydrolytic activity in reaction with organophosphorus compounds (up to 74% of initially applied activity). Materials with the certain enzyme and Zn nanoparticles were more efficient against Bacillus subtilis cells (up to 2.1-fold), and Ta nanoparticles acted preferentially against E scherichia coli (up to 1.5-fold). Some materials were proved to be more suitable for combined modification by metal nanoparticles and His 6 -OPH complexes as antimicrobial protectants.

Despite the brilliant bioactive performance of tantalum as an orthopedic biomaterial verified through laboratory researches and clinical practice in the past decades, scarce evidences about the essential mechanisms of how tantalum contributes to osteogenesis were systematically discussed. Up to now, a few studies have uncovered preliminarily the biological mechanism of tantalum in osteogenic differentiation and osteogenesis; it is of great necessity to map out the panorama through which tantalum contributes to new bone formation. This minireview summarized current advances to demonstrate the probable signaling pathways and underlying molecular cascades through which tantalum orchestrates osteogenesis, which mainly contain Wnt/ β -catenin signaling pathway, BMP signaling pathway, TGF- β signaling pathway, and integrin signaling pathway. Limits of subsistent studies and further work are also discussed, providing a novel vision for the study and application of tantalum., Competing Interests: The authors have no competing interests., (Copyright © 2020 Hu Qian et al.)

Porous tantalum metal with low elastic modulus is similar to cancellous bone. Reticulated vitreous carbon (RVC) can provide three-dimensional pore structure and serves as the ideal scaffold of tantalum coating. In this study, the biocompatibility of domestic porous tantalum was first successfully tested with bone marrow stromal stem cells (BMSCs) in vitro and for bone tissue repair in vivo. We evaluated cytotoxicity of RVC scaffold and tantalum coating using BMSCs. The morphology, adhesion, and proliferation of BMSCs were observed via laser scanning confocal microscope and scanning electron microscopy. In addition, porous tantalum rods with or without autologous BMSCs were implanted on hind legs in dogs, respectively. The osteogenic potential was observed by hard tissue slice examination. At three weeks and six weeks following implantation, new osteoblasts and new bone were observed at the tantalum-host bone interface and pores. At 12 weeks postporous tantalum with autologous BMSCs implantation, regenerated trabecular equivalent to mature bone was found in the pore of tantalum rods. Our results suggested that domestic porous tantalum had excellent biocompatibility and could promote new bone formation in vivo. Meanwhile, the osteogenesis of porous tantalum associated with autologous BMSCs was more excellent than only tantalum implantation. Future clinical studies are warranted to verify the clinical efficacy of combined implantation of this domestic porous tantalum associated with autologous BMSCs implantation and compare their efficacy with conventional autologous bone grafting carrying blood vessel in patients needing bone repairing., (© 2016 by the Society for Experimental Biology and Medicine.)

Osteogenic responses of human mesenchymal stromal cells (hMSCs) were compared on square-patterned, inverse square-patterned, and planar titanium, chromium, diamond-like carbon (DLC), and tantalum; hypothesis was that both the materials and patterns affect osteogenesis. Samples were produced using photolithography and physical vapor deposition. Early-marker alkaline phosphatase (ALP) and mid-markers, small body size and mothers against decapentaplegic-related protein-1 (SMAD1), runt-related transcription factor-2 (RUNX2), and osteopontin were studied using quantitative real-time polymerase chain reaction. ALP and hydroxyapatite, were colorimetrically studied. ALP reached highest values on both patterned titanium samples, but mid-markers disclosed that it was already lagging behind planar and inverse patterned tantalum. Hydroxyapatite formation disclosed that osteo-induced hMSCs passed all the differentiation stages (except on planar chromium). Presence of hydroxyapatite disclosed that both types of patterning promoted (p < 0.001) osteogenesis compared to planar samples. Results suggest that the osseocompatibility/integration of implants could be improved by changing the monotonous and featureless implant-host interface into micro-patterned interface to provide physical differentiation cues.

Nowadays, titanium is a very commonly used biomaterial for the preparation of orthopedic and dental implants. Its excellent mechanical and biochemical bulk properties are nevertheless counterbalanced by its propensity to long term degradation in physiological conditions and its weak osseointegrative capacities. In this context, surface modifications can significantly hinder titanium weaknesses. The approach considered in this work relies on the preparation of thin composite coatings based on tantalum oxide and carbon nanotubes by sol-gel process. Tantalum is particularly interesting for its high biocompatibility and bioactivity, as well as its strong resistance to bio-corrosion. Carbon nanotubes are exploited to reinforce the compactness and homogeneity of the coatings, and can act as a favorable factor to strengthen the interaction with bone components by biomimicry. The composite layers are further modified with specific organophosphonic acid molecular films, able to chemically bind the tantalum oxide surface and improve the hydroxyapatite formation process. The characteristics and the qualities of these hybrid inorganic/organic coatings are evaluated by XPS, SEM, TEM, peeling tests, contact angle measurements, and electrochemical characterizations (free potential, polarization curves)., (Copyright © 2012 Elsevier Inc. All rights reserved.)

We recently determined the crystal structure of the functional core of human U1 snRNP, consisting of nine proteins and one RNA, based on a 5.5 A resolution electron density map. At 5-7 A resolution, alpha helices and beta sheets appear as rods and slabs, respectively, hence it is not possible to determine protein fold de novo. Using inverse beam geometry, accurate anomalous signals were obtained from weakly diffracting and radiation sensitive P1 crystals. We were able to locate anomalous scatterers with positional errors below 2 A. This enabled us not only to place protein domains of known structure accurately into the map but also to trace an extended polypeptide chain, of previously undetermined structure, using selenomethionine derivatives of single methionine mutants spaced along the sequence. This method of Se-Met scanning, in combination with structure prediction, is a powerful tool for building a protein of unknown fold into a low resolution electron density map.

Conventional porous-coated joint prostheses used in hip and knee reconstruction have demonstrated good clinical results, however, these implants possess some inherent shortcomings such as low volumetric porosity, suboptimal frictional characteristics, and higher modulus of elasticity relative to that of bone. Porous tantalum, a novel porous biomaterial was developed to address these limitations. Extensive laboratory studies have revealed that porous tantalum has physical, mechanical and tissue in growth properties that makes it a potentially improved biomaterial particularly in complex joint reconstructions. Porous tantalum is a highly porous biomaterial with good biocompatibility, excellent corrosion resistance, and high coefficient of friction. The short term clinical results of porous tantalum in primary hip, revision hip, and knee reconstructive surgery are encouraging but further studies will be needed to determine whether the theoretical advantages of porous tantalum can provide long term biological fixation and stability. This review presents the biomaterial properties and clinical results of porous tantalum devices in hip and knee reconstructive surgeries.

The quartz crystal microbalance with dissipation (QCM-D) (Q-Sense AB, Sweden) has been established as a useful tool for evaluating interactions between various biological and non-biological systems, and there has been increasing interest in using the QCM-D technique for cell monitoring applications. This study investigated the potential of the QCM-D to characterise the initial adhesion and spreading of cells in contact with protein precoated biocompatible surfaces. The QCM-D technique is attractive for monitoring cell adhesion and spreading as it allows in situ real-time measurements. The adhesion of NIH3T3 (EGFP) fibroblasts to tantalum (Ta) and oxidised polystyrene (PS(ox)) surfaces precoated with serum proteins was examined using the QCM-D for a period of either 2 or 4 h. Time-lapse photography was performed at 30 min intervals to visually examine cell adhesion and spreading in order to relate cell morphology to the QCM-D response. Following adsorption of albumin, fibronectin or newborn calf serum onto the surfaces, QCM-D measurements showed that cells adhered and spread on the fibronectin and serum coated surfaces, while few cells adhered to the albumin coated surfaces. Cells adhered to albumin coated surfaces had a rounded morphology. The responses to fibronectin and serum precoated surfaces were quite different for each of the underlying substrates indicating that the process of cell adhesion and spreading elicits different responses depending on both the protein coating composition and the influence of the underlying substrate. The different response may be due to extracellular matrix remodelling as well as cytoskeletal changes. Frequency (f) and dissipation (D) changes associated with cell adhesion were less than would be expected from the Sauerbrey relation due to the viscoelastic properties of the cells.

Magnetic AC mode (MACmode) atomic force microscopy (AFM) was used to study murine (mouse) MC3T3-E1 preosteoblastic cells attached to biocompatible tantalum substrates. Cell volumes of attached cells derived from AFM images were compared to volumes of detached cells in suspension measured by the Coulter sizing technique. An increase of approximately 50% in cell volume was observed when the cells attached to planar tantalum substrates and developed a flattened structure including lamellipodia. We address thoroughly the issues general to the AFM determination of absolute cell volumes, and compare our magnetic AC mode AFM measurements to hitherto reported cell volume determinations by contact mode AFM.

A tight fixation between bone and implant materials is of great importance for a successful outcome of procedures such as total knee arthroplasty (TKA) and total hip arthroplasty (THA). Surface modification of titanium metal and titanium alloy is one of the attractive methods to improve the biological affinity of orthopedic prostheses. Recent studies reported that titanium substrates were provided with bone-bonding ability, that is, osteoconductivity, through a chemical treatment with hydrogen peroxide solution containing tantalum chloride. The present study investigated the histological and mechanical effects of such treatment of the surface of titanium fiber mesh. Titanium alloy rods of 7.6 x 7.6 x 20 mm that had a titanium fiber mesh of 250 microm were implanted bilaterally into the distal aspect of the femur of adult beagle dogs. At 3, 5, and 8 weeks after implantation, the rods were removed to examine their bonding strength and histological compatibility with bone. Bonding strength was evaluated by the pull-out test. The bonding strength of the treated specimen with bone increased with time, and was faster than that of untreated specimens. At 8 weeks postoperative, the bonding strength of both the treated and untreated specimens became almost equal. The amount of newly formed bone on and in the titanium fiber mesh was significantly increased by the chemical treatment (p<0.05). The rate of bone formation in the fiber mesh was accelerated after chemical treatment. These results indicated that the surface treatment enhanced bone formation in the initial stage thank to the osteoconductive property of the titanium fiber mesh conferred by the chemical treatment so that faster bonding strength was achieved. Surface treatment providing titanium mesh with osteoconductivity has the advantages of the fast healing and tight bonding for prostheses in TKA and THA., (Copyright 2002 Wiley Periodicals, Inc.)

During the Persian Gulf War, soldiers were injured with depleted uranium (DU) fragments. To assess the potential health risks associated with chronic exposure to DU, Sprague Dawley rats were surgically implanted with DU pellets at 3 dose levels (low, medium and high). Biologically inert tantalum (Ta) pellets were used as controls. At 1 day and 6, 12, and 18 months after implantation, the rats were euthanized and tissue samples collected. Using kinetic phosphorimetry, uranium levels were measured. As early as 1 day after pellet implantation and at all subsequent sample times, the greatest concentrations of uranium were in the kidney and tibia. At all time points, uranium concentrations in kidney and bone (tibia and skull) were significantly greater in the high-dose rats than in the Ta-control group. By 18 months post-implantation, the uranium concentration in kidney and bone of low-dose animals was significantly different from that in the Ta controls. Significant concentrations of uranium were excreted in the urine throughout the 18 months of the study (224 +/- 32 ng U/ml urine in low-dose rats and 1010 +/- 87 ng U/ml urine in high-dose rats at 12 months). Many other tissues (muscle, spleen, liver, heart, lung, brain, lymph nodes, and testicles) contained significant concentrations of uranium in the implanted animals. From these results, we conclude that kidney and bone are the primary reservoirs for uranium redistributed from intramuscularly embedded fragments. The accumulations in brain, lymph nodes, and testicles suggest the potential for unanticipated physiological consequences of exposure to uranium through this route.

Self-propagating high temperature reaction waves, leading to the synthesis of advanced materials, are investigated in a variety of heterogeneous reaction systems by using a digital high-speed microscopic video recording technique. It is shown that, although on the macroscopic length and time scales, the reaction appears to move in a steady mode, on the microscopic level it has a complex character that is related to the reaction mechanism.

The title compound Ta6Br(2+)12 is of interest for the analysis of biological structures as a heavy-metal derivative with great potential for the structure determination of large protein systems. In macromolecular crystallography the phases of the measured structure factor amplitudes have to be determined. The most widely used method for novel structures is isomorphous replacement by introducing electron-rich compounds into the protein crystals. These compounds produce measurable changes of the diffraction intensities, which allow phase determination. We synthetized the Ta6Br(2+)12 cluster in high yields, crystallized it, and determined its crystal structure by X-ray diffraction analysis at atomic resolution. The cluster is a regular octahedron consisting of six metal atoms with 12 bridging bromine atoms along the 12 edges of the octahedron. The cluster is compact, of approximately spherical shape with about 4.3 A radius and highly symmetrical. One Ta6Br(2+)12 ion adds 856 electrons to a protein, a considerable contribution to the scattering power even of large proteins or multimeric systems. At low resolution all atoms of the cluster scatter in phase and act as a super heavy-atom, which is easy to locate in the difference Patterson map. We investigated its binding sites in the biologically significant high-resolution structures of an antibody V(L) domain, dimethyl sulfoxide reductase, GTP-cyclohydrolase I, and the proteasome. With the randomly oriented cluster, treated as a single site scatterer, phases could be used only up to 6 A resolution. In contrast, when the cluster is correctly oriented, phases calculated from its 18 atom sites can be used to high resolution. We present the atomic structure of the Ta6Br(2+)12, describe a method to determine its localization and orientation in the unit cell of protein crystals of two different proteins, and analyse its phasing power. We show that phases can be calculated to high resolution. The phase error is lower by more than 30 degrees compared to the single site approximation, using a resolution of 2.2 A. Furthermore, Ta6Br(2+)12 has two different strong anomalous scatterers tantalum and bromine to be used for phase determination.

This article is a review of recent developments of polymer-related stents mainly employed in the coronary arteries, including polymer-coated stents, biostable stents and biodegradable stents. Polymer paving is covered as well. The problems with the stents currently investigated and the development of new stents are discussed.

Roentgenographic demonstration of intraperitoneal organs and the retrosternal lymphatic system was obtained by insufflation of tantalum dust (particel size 1-5 mu) into the peritoneal cavity of 21 rats. No inflammatory reactions could be demonstrated. This contrastmedium remained over a considerably period of time in the peritoneal cavity and lymphnodes. This indicates the slow elimination of this metall.

We describe a chemical separation that may form the basis of a generator system for the short-lived radionuclide Ta-178 (T 1/2 = 9 min). The parent nuclide W-178 (T 1/2 = 21.7 days) is loaded on an anion-exchange column and the daughter eluted with a mixture of dilute hydrochloric acid and hydrogen peroxide. The yields of tantalum and the breakthrough of the tungsten parent as a function of the eluting conditions are discussed, and preliminary animal distribution data are presented for various treatments of the eluant solution.

178Ta is a short lived radionuclide (half life = 9.3 min), which results in favorable radiation exposure compared to 99mTc (half life 6 h). The energy spectrum of 178Ta consists of imageable photons in the 55-65 keV (61.2%) and 93 keV (33.7%) range but also 6% of disintegrations result in photons with energies greater than 500 keV. These high energy photons cause septal penetration in low energy collimators so that resolution is degraded. However, a medium energy collimator prevents the septal penetration of these higher energy photons. Serial blood samples obtained from dog and rabbit models indicate that 178Ta is retained in the blood pool for at least 20-30 min after intravenous injection. The 178Ta appears to be associated with the protein fraction of the plasma and not primarily with the red blood cell fraction as determined by centrifugation and column chromatography. Gated equilibrium blood pool images using 178Ta were comparable in quality to images using the 99mTc labelled red blood cell technique. Therefore, 178Ta may allow comparable equilibrium gated blood pool imaging with much more favorable radiation dosimetry. Thus, serial studies over prolonged periods of observation may be obtained.

Despite its 9.3-min half-life, Ta-178 can be used to produce radiopharmaceuticals for lung and liver imaging. A variety of human serum albumin microspheres and other particulate radiopharmaceuticals were labeled with Ta-178. A period of approximately 10 min was required for their preparation and administration to rats. Extrapolation to the clinical situation suggests that imaging could take place after one half-life of the nuclide has elapsed. We found that satisfactory imaging is possible using Ta-178 radiopharmaceuticals with the Anger camera and a pinhole collimator. Since short imaging times, high spatial resolution, and low patient doses are reasonable objectives in pediatric scintigraphy, these new radiotracers may prove useful for lung and liver imaging in children.

Studies of pylmonary clearance of tantalum dust labeled with 182Ta in dogs have been extended to as far as 816 days postexposure in order to substantiate earlier pulmonary retention data, examine lymphatic uptake, and seek long-term pathological changes. Exposure to 5-mug and 10-mug powders was compared with the results of earlier 1-mug studies. The 2.1-year long-term clearance half-time of 1-mug powder was confirmed, while the 5-mug and 10-mug powders were found to have a mean long-term retention half-time of 333 days. All three particle sizes demonstrated rapid postinsufflation uptake by the pulmonary lymph nodes, followed by either retention or very slow clearance. No tantalum-induced pathological changes were found on histological examination.

Techniques of body radioactivity measurement were used to study the clearance of activated tantalum oxide accidentally inhaled by three reactor workers. The whole-body retention after 7 days was about 1% of the initial deposit. In one subject studied for a further 424 days the residual activity in the thorax was cleared with a biological half-life of about 1,400 days. The results support indications from other studies that tantalum powder administered in aerosol bronchography may be subject to prolonged alveolar retention.

The in- and outflow of 204Tl, 86Rb and 137Cs in a snail brain was studied. The inward rate constants determined in the presence and without ouabain decreased as follows: Tl+ greater than Rb+ greater than Cs+. The inflow rate constants differed about 2-3 fold. Rates of leakage of the cations were nearly similar, so that Tl+ approximately or equal to Rb+ greater than Cs+. A Na ouabain-sensitive outward transport in a K-free medium containing 0.1-0.2 mM Tl was as high as that in the presence of 1.6 mM external K. A further increase of external Tl inhibited the ouabain-sensitive Na transport. The intracellular distribution of Tl studied by microprobe analysis was found to be similar to that of K. There was a close resemblance of the ouabain-sensitive K-transporting system in the snail brain cells and that in other types of cells including human red cells in their selectivity to Tl+, Rb+ and Cs+. On the contrary, a passive permeability of neurons to Tl+ being similar to that of muscle cells was about 50-100 times less than a Tl+ permeability of inexcitable red cell membrane.