A New α + ß Ti-15Nb Alloy with Low Elastic Modulus: Characterization and In Vitro Evaluation on Osteogenic Phenotype.

This study aimed to produce Ti-15Nb alloy with a low elastic modulus, verify its biocompatibility, and determine whether the alloy indirectly influences cellular viability and morphology, as well as the development of the osteogenic phenotype in cells cultured for 2, 3, and 7 days derived from rat calvarias. Two heat treatments were performed to modify the mechanical properties of the alloy where the Ti-15Nb alloy was heated to 1000 °C followed by slow (-5 °C/min) (SC) and rapid cooling (RC). The results of structural and microstructural characterization (XRD and optical images) showed that the Ti-15Nb alloy was of the α + ß type, with slow cooling promoting the formation of the α phase and rapid cooling the formation of the ß phase, altering the values for the hardness and elastic modulus. Generally, a more significant amount of the α phase in the Ti-15Nb alloy increased the elastic modulus value but decreased the microhardness value. After the RC treatment, the results demonstrated that the Ti-15Nb alloy did not present cytotoxic effects on the osteogenic cells. In addition, we did not find variations in the cell quantity in the microscopy results that could suggest cell adhesion or proliferation modification.

Exoantigens of Paracoccidioides spp. Promote Proliferation and Modulation of Human and Mouse Pulmonary Fibroblasts.

Paracoccidioidomycosis (PCM) is a systemic granulomatous fungal infection caused by thermally dimorphic fungi of the genus Paracoccidioides. Endemic in Latin America, PCM presents with high incidence in Brazil, Colombia, and Venezuela, especially among rural workers. The main clinical types are acute/subacute (AF) form and chronic form (CF). Even after effective antifungal treatment, patients with CF usually present sequelae, such as pulmonary fibrosis. In general, pulmonary fibrosis is associated with dysregulation wound healing and abnormal fibroblast activation. Although fibrogenesis is recognized as an early process in PCM, its mechanisms remain unknown. In the current study, we addressed the role of Paracoccidioides spp. exoantigens in pulmonary fibroblast proliferation and responsiveness. Human pulmonary fibroblasts (MRC-5) and pulmonary fibroblasts isolated from BALB/c mice were cultivated with 2.5, 5, 10, 100, and 250 µg/ml of exoantigens produced from P. brasiliensis (Pb18 and Pb326) and P. lutzii (Pb01, Pb8334, and Pb66) isolates. Purified gp43, the immunodominant protein of P. brasiliensis exoantigens, was also evaluated at concentrations of 5 and 10 µg/ml. After 24 h, proliferation and production of cytokines and growth factors by pulmonary fibroblasts were evaluated. Each exoantigen concentration promoted a different level of interference of the pulmonary fibroblasts. In general, exoantigens induced significant proliferation of both murine and human pulmonary fibroblasts (p < 0.05). All concentrations of exoantigens promoted decreased levels of IL-6 (p < 0.05) and VEGF (p < 0.05) in murine fibroblasts. Interestingly, decreased levels of bFGF (p < 0.05) and increased levels of TGF-ß1 (p < 0.05) and pro-collagen I (p < 0.05) were observed in human fibroblasts. The gp43 protein induced increased TGF-ß1 production by human cells (p = 0.02). In conclusion, our findings showed for the first time that components of P. brasiliensis and P. lutzii interfered in fibrogenesis by directly acting on the biology of pulmonary fibroblasts.

Development of novel Ti-Mo-Mn alloys for biomedical applications.

Due to excellent biocompatibility and corrosion resistance, the application of titanium alloys in orthopedic and dental implants has been increasing since the 1970s. However, the elasticity of these alloys as measured by their Young's modulus is still about two to four times higher than that of human cortical bone. The most widely used titanium alloy for biomedical applications is Ti-6Al-4V, however, previous studies have shown that the vanadium used in this alloy causes allergic reactions in human tissue and aluminum, also used in the alloy, has been associated with neurological disorders. To solve this problem, new titanium alloys without the presence of these elements and with the addition of different elements, usually beta-stabilizers, are being developed. Manganese is a strong candidate as an alloying element for the development of new beta-type titanium alloys, due to its abundance and low cytotoxicity. In this study, Ti-10Mo-5Mn, Ti-15Mo-2.5Mn and Ti-15Mo-5Mn alloys were prepared in an arc furnace, which resulted in an alloy structure clearly showing the predominance of the beta phase with a body-centered cubic crystalline structure. The observed microstructure confirmed the results on the structural characterization of alloys. Measurement of the indirect cytotoxicity of the alloys showed that the extracts of the studied alloys are not cytotoxic for fibroblastic cells.

Preparation, structural, microstructural, mechanical and cytotoxic characterization of as-cast Ti-25Ta-Zr alloys.

Titanium alloys have been widely used as biomaterials, especially for orthopedic prostheses and dental implants, but these materials have Young's modulus almost three times greater than human cortical bones. Because of this, new alloys are being produced for the propose of decreasing Young's modulus to achieve a more balanced mechanical compatibility with the bone. In this paper, it is reported the development of Ti-25Ta alloys as a base material, in which was introduced zirconium, with concentration varying between 0 and 40 wt%, with the aim of biomedical applications. The alloys were prepared in an arc-melting furnace. The microstructural analysis was performed by x-ray diffraction as well as optical and scanning electron microscopy. Selected mechanical properties were analyzed by microhardness and Young's modulus measurements, and cytotoxicity analysis by indirect test. X-ray measurements revealed the presence of α″ phase in the alloy without zirconium; α″ + ß phases for alloys with 10, 20, and 30 wt% of zirconium, and ß phase only for the alloy with 40 wt% of zirconium. These results were corroborated by the microscopy results. The hardness of the alloy was higher than that of cp-Ti due to the actions of zirconium and tantalum as hardening agents. The Young's modulus decreases with high levels of zirconium due to the stabilization of the ß phase. The cytotoxicity test showed that the extracts of studied alloys are not cytotoxic for osteoblast cells in short periods of culture.

Preparation, structural, microstructural, mechanical, and cytotoxic characterization of Ti-15Nb alloy for biomedical applications.

Titanium alloys are widely used in the biomedical field due to their excellent resistance to corrosion, high mechanical strength/density ratio, low elastic modulus, and good biocompatibility. Niobium is a ß-stabilizer element that has the potential to decrease elastic modulus and possesses excellent corrosion resistance. In this article, Ti-15Nb alloy was prepared via arc-melting, with the aim of using it in biomedical applications to replace implants that fail due to mechanical incompatibility with human bone. This Ti-15Nb alloy was structurally, chemically, and microstructurally characterized. Its mechanical properties were analyzed via Vickers microhardness and elastic modulus measurements. The cytotoxicity of the alloy was evaluated via direct and indirect MTT tests. In the direct MTT test, the cells were grown on alloy and in the indirect test, Ti-15Nb alloy extracts were prepared (1 g/1 mL at 310 K for 48 hours). The results of chemical composition showed that the alloy produced has good quality and low content of gaseous impurities, such as oxygen and nitrogen. The obtained results for structure and microstructure indicated the presence of the martensite α' phase. The microhardness of the Ti-15Nb alloy is superior to that of cp-Ti due to solid solution hardening, and the alloy has a better elastic modulus as compared to pure titanium. Cytotoxic effects were not observed. The Ti-15Nb alloy shows good results of mechanical properties and does not show cytotoxic effects. In addition, morphological variations were not found in the cells and good cell adhesion in all the studied conditions was observed. In general, the alloy proposed in this article has satisfactory characteristics as a biomedical material.

In Vitro Cytotoxicity of a Ti-35Nb-7Zr-5Ta Alloy Doped with Different Oxygen Contents.

Cp-Ti is the most common material used for dental implants, but its elastic modulus is around five times higher than that of bone. Recently, promising alloys that add Nb, Ta, Zr and Mo to Ti have been developed. The mechanical properties of these alloys are directly related to its microstructure and the presence of interstitial elements, such as oxygen, carbon, nitrogen and hydrogen. In this study, the in vitro cytotoxicity of Ti-35Nb-7Zr-5Ta (TNZT) alloys was analyzed in the as-received condition and after being doped with several small quantities of oxygen on a cultured osteogenic cell. The cell's morphology was also examined by scanning electron microscopy (SEM). The TNZT alloy presented no cytotoxic effects on osteoblastic cells in the studied conditions.

Influence of heat treatment and oxygen doping on the mechanical properties and biocompatibility of titanium-niobium binary alloys.

The most commonly used titanium (Ti)-based alloy for biological applications is Ti-6Al-4V, but some studies associate the vanadium (V) with the cytotoxic effects and adverse reactions in tissues, while aluminum (Al) has been associated with neurological disorders. Ti-Nb alloys belong to a new class of Ti-based alloys with no presence of Al and V and with elasticity modulus values that are very attractive for use as a biomaterial. It is well known that the presence of interstitial elements (such as oxygen, for example) changes the mechanical properties of alloys significantly, particularly the elastic properties, the same way that heat treatments can change the microstructure of these alloys. This article presents the effect of heat treatment and oxygen doping in some mechanical properties and the biocompatibility of three alloys of the Ti-Nb system, characterized by density measurements, X-ray diffraction, optical microscopy, Vickers microhardness, in vitro cytotoxicity, and mechanical spectroscopy.