Effect of silicon content on the microstructure evolution, mechanical properties, and biocompatibility of ß-type TiNbZrTa alloys fabricated by laser powder bed fusion.

Beta-type titanium alloys are excellent candidates for biomedical applications because of their very low elastic modulus, excellent corrosion resistance, and biocompatibility. However, many traditional ß-type titanium alloys exhibit low yield strength. In this study, a small amount of Si (3 and 5 at.%) was added to a Ti-35Nb-7Zr-5Ta (wt%, TNZT) biomedical alloy prepared via laser powder bed fusion (LPBF) to increase its yield strength. The Si addition resulted in a significant increase in the compression yield strength of the alloy (from 802 to 1282 MPa). Meanwhile, the elastic moduli of the TNZT alloys (48.7-60.6 GPa) with 3 and 5 at.% Si were much lower than that of the Ti-6Al-4 V alloy (110 GPa), which is used extensively in clinical applications. The microstructural analyses indicated that the ultrahigh-strength of the TNZT alloy containing Si was due to the presence of ultrafine (Ti, Nb, Zr)5Si3 (S1) grains in the ß-Ti matrix. In addition, thin shell-shaped S1 and (Ti, Nb, Zr)2Si (S2) grains precipitated along the columnar ß-Ti grain boundaries in the TNZT alloys containing 3 and 5 at.% Si, respectively. Moreover, the introduction of Si to the TNZT alloy significantly refined the grains, weakened the cubic texture, decreased surface roughness, and improved Vickers hardness. The ultrahigh strength of the Si-containing TNZT alloys was due to grain boundary strengthening and precipitation strengthening. In addition, in vitro studies with MC3T3-E1 cells revealed that the cytocompatibilities of the LPBF-fabricated TNZT and Si-containing TNZT alloys were equivalent and were better than that of the LPBF-fabricated Ti-6Al-4 V alloy. In particular, the TNZT alloy with 3 at.% Si showed the best elastic modulus (48.7 ± 1.0 GPa), yield strength (1151 ± 17 MPa), and cell biological response among all the alloys investigated in this study, and hence was found to be a suitable candidate for application in load-bearing bone implants.

Influence of press-fit parameters on the primary stability of uncemented femoral resurfacing implants.

Primary stability is essential to the success of uncemented prostheses. It is strongly influenced by implantation technique, implant design and bone quality. The goal of this study was to investigate the effect of press-fit parameters on the primary stability of uncemented femoral head resurfacing prostheses. An in vitro study with human specimens and prototype implants (nominal radial interference 170 and 420 microm) was used to investigate the effect of interference on primary stability. A finite element model was used to assess the influence of interference, friction between implant and bone, and bone quality. Primary stability was represented by the torque capacity of the implant. The model predicted increasing stability with actual interference, bone quality and friction coefficient; plastic deformation of the bone began at interferences of less than 100 microm. Experimentally, however, stability was not related to interference. This may be due to abrasion or the collapse of trabecular bone structures at higher interferences, which could not be captured by the model. High nominal interferences as tested experimentally appear unlikely to result in improved stability clinically. An implantation force of about 2,500 N was estimated to be sufficient to achieve a torque capacity of about 30 N m with a small interference (70 microm).

Effect of thermomechanical processing on the mechanical biofunctionality of a low modulus Ti-40Nb alloy.

Different hardening strategies were evaluated regarding their potential to improve the mechanical biofunctionality of the cast and solution-treated low modulus ß-Ti alloy Ti 40Nb. The strategies are based on thermomechanical treatments comprised of different hot- and cold-rolling steps, as well as annealing treatments aiming at the successive exploitation of different hardening mechanisms (grain boundary hardening, work hardening and precipitation hardening). Quasi-static tensile testing revealed that grain refinement by one order of magnitude has only a small impact on improving the mechanical biofunctionality of Ti-40Nb. However, work hardening effectively improves the tensile strength by 30% to a value of 650MPa, while retaining Young׳s modulus at 60GPa. The α-phase precipitation hardening was verified to have an increasing effect on both, strength and Young׳s modulus. Thereby, the change of Young׳s modulus dominates the change of the strength, even at low α-phase fractions. The pseudo-elastic behavior of Ti 40Nb is discussed under consideration of the microstructural changes due to the thermomechanical treatment. The texture changes evolving upon cold-rolling markedly influence the recrystallization behavior. However, the present results do not show a significant effect of the texture on the mechanical properties of Ti-40Nb.

M cells in Peyer's patches of the intestine.

M cells are specialized epithelial cells of the mucosa-associated lymphoid tissues. A characteristic of M cells is that they transport antigens from the lumen to cells of the immune system, thereby initiating an immune response or tolerance. Soluble macromolecules, small particles, and also entire microorganisms are transported by M cells. The interactions of these substances with the M cell surface, their transcytosis, and the role of associated lymphoid cells are reviewed in detail. The ultrastructure and several immuno- and lectin-histochemical properties of M cells vary according to species and location along the intestine. We present updated reports on these variations, on identification markers, and on the origin and differentiation of M cells. The immunological significance of M cells and their functional relationship to lymphocytes and antigenpresenting cells are critically reviewed. The current knowledge on M cells in mucosa-associated lymphoid tissues outside the gut is briefly outlined. Clinical implications for drug deliver, infection, and vaccine development are discussed.

Human polymorphonuclear neutrophils express a B7-1-like molecule.

Polymorphonuclear neutrophils (PMN) are part of the innate immune system and are first-line effector cells in acute inflammatory responses. On activation PMNs secrete cytokines and oxygen metabolites that might be involved in the regulation of the acquired immune response. We show here that peripheral blood PMNs constitutively express a B7-1-like molecule as detected by immunostaining with several B7-1 antibodies. Reverse transcriptase-polymerase chain reaction using three sets of primers spanning different regions of B7-1 indicate dissimilarities at the mRNA level. B7-1 mRNA is expressed in bone marrow cells and lipopolysaccharide (LPS)-stimulated but not in unstimulated PMNs. The B7-1-like molecule is localized to the cytoplasmic granules and translocated to the cell surface after stimulation with LPS or interleukin-12 in some donors. Binding of CTLA4-Ig suggests that the B7-1-like molecule can interact with functional B7 ligand and might be important in the immunobiology of PMNs.

Nanostructured Ti-Zr-Pd-Si-(Nb) bulk metallic composites: Novel biocompatible materials with superior mechanical strength and elastic recovery.

The microstructure, mechanical behaviour, and biocompatibility (cell culture, morphology, and cell adhesion) of nanostructured Ti45 Zr15 Pd35- x Si5 Nbx with x = 0, 5 (at. %) alloys, synthesized by arc melting and subsequent Cu mould suction casting, in the form of rods with 3 mm in diameter, are investigated. Both Ti-Zr-Pd-Si-(Nb) materials show a multi-phase (composite-like) microstructure. The main phase is cubic ß-Ti phase (Im3m) but hexagonal α-Ti (P63/mmc), cubic TiPd (Pm3m), cubic PdZr (Fm3m), and hexagonal (Ti, Zr)5 Si3 (P63/mmc) phases are also present. Nanoindentation experiments show that the Ti45 Zr15 Pd30 Si5 Nb5 sample exhibits lower Young's modulus than Ti45 Zr15 Pd35 Si5 . Conversely, Ti45 Zr15 Pd35 Si5 is mechanically harder. Actually, both alloys exhibit larger values of hardness when compared with commercial Ti-40Nb, (HTi-Zr-Pd-Si ≈ 14 GPa, HTi-Zr-Pd-Si-Nb ≈ 10 GPa and HTi-40Nb ≈ 2.7 GPa). Concerning the biological behaviour, preliminary results of cell viability performed on several Ti-Zr-Pd-Si-(Nb) discs indicate that the number of live cells is superior to 94% in both cases. The studied Ti-Zr-Pd-Si-(Nb) bulk metallic system is thus interesting for biomedical applications because of the outstanding mechanical properties (relatively low Young's modulus combined with large hardness), together with the excellent biocompatibility.

Costimulatory molecules B7-1 and B7-2 on CSF cells in multiple sclerosis and optic neuritis.

The aberrant expression of B7 costimulatory molecules is involved in the pathogenesis of autoimmune diseases and overexpression of B7-1 was found in inflammatory multiple sclerosis (MS) lesions. We here report that costimulatory molecules B7-1 and B7-2 are expressed on cerebrospinal fluid (CSF) monocytes and B-lymphocytes from patients with MS, optic neuritis (ON) and other inflammatory central nervous system (CNS) diseases. In patients with ON but not MS, increased expression of B7-2 was detected as compared to non-inflammatory controls. The expression of B7-1 in MS and ON patients correlates with disease duration but not with relapses in patients with MS indicating a role in early disease but not as a reliable marker of disease activity at later stages of MS.

M-cells in the rabbit tonsil exhibit distinctive glycoconjugates in their apical membranes.

The tonsil crypt epithelium contains membranous (M)-cells that transport antigens from the lumen to underlying lymphoid cells, thereby initiating specific immune responses. Mechanisms mediating the adhesion of antigens to the M-cell surface are important for effective and selective uptake of potential pathogens but are still poorly understood. Therefore, the carbohydrates present on crypt epithelial cells of the rabbit palatine tonsil were studied by lectin histochemistry. Ultrathin LR White sections were incubated with a panel of eight lectins conjugated to colloidal gold or biotin. The glycocalyx of the apical membrane of M-cells was selectively labeled by UEA-I, LTA, HPA, and VVA, whereas that of the remaining squamous epithelial cells preferentially bound RCA-I and PNA. WGA and ConA showed only little binding, with no discernible preference for any of the cell types. Double labeling of UEA-1 together with anti-vimentin antibodies revealed that UEA-I-positive epithelial cells also contained the rabbit M-cell marker vimentin, and vice versa. The results show that a specific composition of glycoconjugates, which differs from that on squamous epithelial cells, is found on M-cells of the rabbit tonsil. The M-cell-specific glycoproteins and glycolipids could be selectively targeted by microorganisms that adhere to M-cells and enter the host along this pathway.

Glycoconjugate expression defines the origin and differentiation pathway of intestinal M-cells.

Intestinal M-cells are specialized epithelial cells located in the domes of the gut-associated lymphoid tissues, which transport antigens from the lumen to the underlying lymphoid tissue, thereby initiating immune reactions. It is assumed that M-cells arise from stem cells in the crypts, from which they migrate to the top of the domes. To study the differentiation pathway of M-cells, we used the rabbit cecal lymphoid patch in which the M-cells express high levels of alpha 1-2-linked fucose and N-acetyl-galactosamine residues in their apical membrane. Dome areas were labeled with fluorescein- and rhodamine-conjugated lectins specific for alpha 1-2-linked fucose and N-acetyl-galactosamine in vivo and in vitro, and were observed with confocal laser scanning microscopy. Ultrathin sections were double labeled with lectin-gold conjugates and the labeling density was quantified by computer-based image analysis. All cecal patch M-cells expressed alpha 1-2-linked fucose and N-acetyl-galactosamine, but the amount of the two saccharides varied considerably depending on the position of the M-cells at the base, flank, or top of the dome. In eight of 18 rabbits studied, radial strips of M-cells with common glycosylation patterns were observed, each strip associated with an individual crypt. Confocal microscopy revealed that lectin-labeled M-cells were not restricted to the dome epithelium but were also detected in the upper third of crypts surrounding the domes. The results show that M-cells are heterogeneous concerning the glycosylation pattern of membrane glycoconjugates. This pattern is modified as the M-cells differentiate and migrate from the base to the top of the dome. Radial strips of M-cells with a common proclivity of glycoconjugate expression suggest that those M-cells that derive from the same crypt have a clonal origin. The presence of (pre-) M-cells in the crypts surrounding the domes indicates that M-cells derive directly from undifferentiated crypt cells and do not develop from differentiated enterocytes.

Brush cells of the mouse intestine possess a specialized glycocalyx as revealed by quantitative lectin histochemistry. Further evidence for a sensory function.

Brush cells occur in the epithelium of the small intestine and in various other epithelia of endodermal origin. Ultrastructural and histochemical characteristics suggest that they represent sensory cells. Because the apical membrane of brush cells might be involved in and specialized for (chemo-)receptive functions, we investigated the composition of the glycocalyx and compared it with that of enterocytes. Ultrathin sections of murine small intestine were labeled with a panel of eight lectins. Their binding sites in the brush border and on vesicles of the apical cytoplasm were detected by colloidal gold and quantified using image analysis. The glycocalyx of brush cells contained significantly higher amounts of l-fucose residues than that of enterocytes, as detected by the lectins UEA-I and LTA. In contrast, most of the other lectins bound more avidly to the glycocalyx of enterocytes. The cytoplasmic vesicles closely resembled the apical membrane in their labeling pattern. Quantitation of the brush cells' distribution revealed that the epithelia of the Peyer's patches contained 10-fold higher numbers of brush cells than the small intestinal mucosa distant from lymphoid tissue. We conclude that brush cells possess a glycocalyx with a specialized composition and differ significantly from enterocytes. Because similar peculiarities of the apical membrane have previously been described for sensory cells of the olfactory and gustatory organs, this study provides further evidence in favor of a sensory function of brush cells.

A simple method for the acquisition of high-quality digital images from analog scanning electron microscopes.

A method is described for converting video signals of analog scanning electron microscopes (SEMs) into digital images of high quality. A plug-in card commercially available for personal computers is used for the on-line analog/digital conversion. A Windows application program written by the authors, together with low-level software drivers supplied with the plug-in card, allow digital images to be recorded, to be displayed simultaneously on the computer monitor and to be saved as a file in a standardized format. Compared to conventional photographic images obtained from the SEM camera system, the digital images possess superior sharpness of outline, excellent image definition, diminished noise and well-defined grey-scale tones. This method provides SEM images of high quality for less than $1000 from most older analog SEMs. In addition, the advantages of digital image processing can be applied to analog SEMs, including contrast enhancement, digital filtering and multichannel recording.

M cells in the rabbit palatine tonsil: the distribution, spatial arrangement and membrane subdomains as defined by confocal lectin histochemistry.

The crypt epithelium of the palatine tonsil contains M cells that play an important role in the uptake of luminal antigens to initiate immune responses. To study the close interaction of M cells, squamous epithelial cells and lymphocytes we used confocal laser scanning microscopy and the lectin from Ulex europaeus (UEA-I), which selectively labels rabbit tonsillar M cells. Confocal serial sections and synthetic section planes showed that the M cells comprise up to 35% of the epithelial cells in the tonsil crypt and completely engulf clusters of two to eight lymphocytes with their apical cytoplasm. These lymphocytes lie in a pocket of the M cell's basolateral membrane that invaginates from one of the lateral aspects and forms a tunnel-like opening. Therefore, the tonsillar M cells closely resemble the M cells of the small and large intestines in their spatial structure, and likewise maintain an intraepithelial compartment for the interaction of lymphocytes, macrophages and antigens. The UEA-I bound intensely to the apical membrane of the M cells and to transcytotic vesicles in the apical cytoplasm. The pocket membrane bound the UEA-I more avidly than the remaining basolateral membrane, suggesting that the basolateral membrane of M cells is subdivided into membrane domains with different compositions of glycoconjugates.

Use of a digital film scanner to enhance low-power bright field photomicrography.

Low-power bright field photomicrographs often suffer from insufficient sharpness, uneven illumination, and colour hues. Using a film scanner, commercially available and designed for digitizing 35-mm transparencies, we directly scanned microscopic slides that carried dye-labelled and stained sections. The digital images covered a field of up to 24 x 36 mm and revealed excellent sharpness, absolutely even illumination and superior colour reproduction as compared to conventional photomicrographs taken with binoculars, macro lenses, or microscopes. As the method requires neither specialized instrumentation nor expert knowledge of photomicrographic techniques, it reduces costs and saves time. The high-quality digital survey micrographs can easily be used for image processing, image analysis and morphometry. Thus, this new method is valuable not only for pathology, embryology, histochemistry, and the neurosciences, but also for the exchange of low-power micrographs via the internet and for computer media that are increasingly used in medical education.

Morphology and immunology of the human palatine tonsil.

At the surface of the respiratory and digestive organs the organism first comes into contact nasally and orally with various foreign agents and substances in the air and in food. The palatine tonsils are located at the centre of this strategic region. Immunological processes, both humoral and cellular, are initiated in the different specialised compartments of the palatine tonsils, such as the crypt epithelium, lymphoid follicles and extrafollicular region. Each compartment has a typical composition of lymphocytes and dendritic cell subsets. This review summarises current data on the anatomy, histology, and pathology of the human palatine tonsils, describes their fundamental immunological functions, and provides insight into the various interactions involved in the initiation of immune responses. The palatine tonsil is the only easily accessible human lymphoid organ and is often taken as an example for lymphoid organs. Although affections of the palatine tonsils constitutes an essential part in the clinical routine, it is still controversial whether tonsillectomy is of general benefit. This is of increasing importance since it has been discovered in the last few years that the palatine tonsils are reservoir and replication sites of HIV.

The rabbit M-cell marker vimentin is present in epithelial cells of the tonsil crypt.

The epithelium of the rabbit palatine tonsil was studied with vimentin immunohistochemistry, using cryosections and paraffin sections labelled with three monoclonal antibodies. Vimentin-positive epithelia[ cells were detected in crypt regions overlying lymphoid follicles but were absent from the surrounding stratified pharyngeal epithelium. The cells lay in close contact with intra-epithelial lymphocytes and their apical cytoplasm had a membranous shape. Since vimentin is a sensitive, specific marker for M-cells of the rabbit intestine, the present findings indicate that M-cells similar to those in the gut-associated lymphoid tissue occur in the tonsil.

Linear arrays of intramembranous particles characterize a subpopulation of epithelial cells in the rabbit caecum.

Linear arrays of particles, identical to those in the cup cells of the small intestine, characterize the brush border membrane of a subpopulation of surface epithelial cells in freeze-fracture replicas of the rabbit caecum. Although these cells lack a cup-like indentation of their brush border, we propose that all intestinal epithelial cells showing this arrangement of intramembranous particles in their apical membrane belong to a distinct subpopulation of the epithelial cells. A specific function of this cell type that is related to the linear arrays of particles remains to be determined.

[Scientific theory and planning in the health fields]. / Wissenschaftstheorie und Planung im Gesundheitswesen.

One of the most important function of philosophy of science is to elucidate terms and to discuss the possibilities to decide about values--both problems have practical relevance for the interaction between science, policy and politics in planning. Within planning theory it is striking, that in most cases the critical point of rationality is not treated adequately. Organization, functions and norms in the field of science and administration decide upon the forms of cooperation of social medicine in planning.

[Comparative analysis of in vitro test procedures for evaluating hemocompatibility of cardiovascular stents]. / Vergleichende Analyse von in vitro Testverfahren zur Beurteilung der Hämokompatibilität von kardiovaskulären Stents.

Within the scope of this study existing in vitro techniques for testing the hemocompatibility of coronary stents were analysed and optimised. Static and quasi-stationary systems were compared to a pulsed flow model with respect to platelet activity. The streamlines were visualized by dye injection. Blood flow was measured by ultrasonic Doppler velocity meter and electromagnetic flow meter. Uncoated stainless steel (316 L) stents were tested. Surrogate parameters of the hemocompatibility were the change in surface morphology after blood contact and the rise of biomechanical activation markers as C3a and beta-thromboglobulin. The results were correlated to the stent design and to the flow characteristics of the test systems.

Chemical nanoroughening of Ti40Nb surfaces and its effect on human mesenchymal stromal cell response.

Samples of low modulus beta-type Ti40Nb and cp2-Ti were chemically treated with 98% H2 SO4 + 30% H2 O2 (vol. ratio 1:1) solution. Surface analytical studies conducted with HR-SEM, AFM, and XPS identified a characteristic nanoroughness of the alloy surface related with a network of nanopits of ∼25 nm diameter. This is very similar to that obtained for cp2-Ti. The treatment enhances the oxide layer growth compared to mechanically ground states and causes a strong enrichment of Nb2 O5 relative to TiO2 on the alloy surface. The in vitro analyses clearly indicated that the chemical treatment accelerates the adhesion and spreading of human mesenchymal stromal cells (hMSC), increases the metabolic activity, and the enzyme activity of tissue non-specific alkaline phosphatase (TNAP). Surface structures which were generated mimic the cytoplasmic projections of the cells on the nanoscale. Those effects are more pronounced for the Ti40Nb alloy than for cp2-Ti. The relation between alloy surface topography and chemistry and cell functions is discussed.