Effect of the Nanorough Surface of TiO2 Thin Films on the Compatibility with Endothelial Cells.

The cytocompatibility of titanium oxides (TiO2) and oxynitrides (N-TiO2, TiOxNy) thin films depends heavily on the surface topography. Considering that the initial relief of the substrate and the coating are summed up in the final topography of the surface, it can be expected that the same sputtering modes result in different surface topography if the substrate differs. Here, we investigated the problem by examining 16 groups of samples differing in surface topography; 8 of them were hand-abraded and 8 were machine-polished. Magnetron sputtering was performed in a reaction gas medium with various N2:O2 ratios and bias voltages. Abraded and polished uncoated samples served as controls. The surfaces were studied using atomic force microscopy (AFM). The cytocompatibility of coatings was evaluated in terms of cytotoxicity, adhesion, viability, and NO production. It has been shown that the cytocompatibility of thin films largely depends on the surface nanostructure. Both excessively low and excessively high density of peaks, high and low kurtosis of height distribution (Sku), and low rates of mean summit curvature (Ssc) have a negative effect. Optimal cytocompatibility was demonstrated by abraded surface with a TiOxNy thin film sputtered at N2:O2 = 1:1 and Ub = 0 V. The nanopeaks of this surface had a maximum height, a density of about 0.5 per 1 µm2, Sku from 4 to 5, and an Ssc greater than 0.6. We believe that the excessive sharpness of surface nanostructures formed during magnetron sputtering of TiO2 and N-TiO2 films, especially at a high density of these structures, prevents both adhesion of endothelial cells, and their further proliferation and functioning. This effect is apparently due to damage to the cell membrane. At low height, kurtosis, and peak density, the main factor affecting the cell/surface interface is inefficient cell adhesion.

Silent HDV epidemics culminates in high levels of liver cirrhosis in endemic region despite 20 years of HBV vaccination.

The hepatitis delta virus (HDV) is believed to be a vanishing infection in countries with successful hepatitis B virus (HBV) vaccination programs. We assessed the current status of HDV infection in Tuva, a region of the Russia that has been highly endemic for HBV. The proportion of HDV-infected patients among HBsAg-positive patients in the regional registry in 2020 was 32.7% (786/2401). An analysis of the medical records of 514 HDV patients demonstrated that 37.5% (193/514) had liver cirrhosis at the first doctor's visit, and 7.4% of patients lived in families where another family member had HDV. All HDV patients were infected with genotype HDV-1, 94.5% had HBV genotype D, and 5.5% had genotype A. A serosurvey conducted among 1170 healthy volunteers showed that the average detection rate of HBsAg with anti-HDV was 1.0% (95% CI: 0.57-1.81%). No anti-HDV positive samples were detected in participants aged under 30 years. The HBsAg/anti-HDV positivity rate peaked at 7.4% in patients aged 50-59 years, which was significantly higher than in a similar age cohort surveyed in 2008 (1.6%, p < .0001). A Bayesian analysis showed that HDV circulation in Tuva resulted from two waves of introduction, the first in the 1810s (95% HPD: 1741-1834) from Central Asia, and the second in the 1960s (95% HPD: 1953-1979) from Russia. HBV has a much longer history of circulation in Tuva with the MRCA for the predominant genotype HBV-D dated to 972 (95% HPD: 535-1253) for subtype D1, 1274 (95% HPD: 936-1384) for D2, and 1173 (95% HPD: 1005-1618) for D3. A SkyGrid reconstruction of population dynamics showed an increase in the intensity of HDV spread in recent decades. This situation shows the need for HDV screening and prevention measures among people living with HBV.

Integral Algorithms to Evaluate TiO2 and N-TiO2 Thin Films' Cytocompatibility.

Titanium oxide (TiO2) and oxynitride (N-TiO2) coatings can increase nitinol stents' cytocompatibility with endothelial cells. Methods of TiO2 and N-TiO2 sputtering and cytocompatibility assessments vary significantly among different research groups, making it difficult to compare results. The aim of this work was to develop an integral cytocompatibility index (ICI) and a decision tree algorithm (DTA) using the "EA.hy926 cell/TiO2 or N-TiO2 coating" model and to determine the optimal cytocompatible coating. Magnetron sputtering was performed in a reaction gas medium with various N2:O2 ratios and bias voltages. The samples' morphology was studied by scanning electron microscopy (SEM) and Raman spectroscopy. The cytocompatibility of the coatings was evaluated in terms of their cytotoxicity, adhesion, viability, and NO production. The ICI and DTA were developed to assess the cytocompatibility of the samples. Both algorithms demonstrated the best cytocompatibility for the sample sputtered at Ubias = 0 V and a gas ratio of N2:O2 = 2:1, in which the rutile phase dominated. The DTA provided more detailed information about the cytocompatibility, which depended on the sputtering mode, surface morphology, and crystalline phase. The proposed mathematical models relate the cytocompatibility and the studied physical characteristics.

Nitrogen-doped titanium dioxide films fabricated via magnetron sputtering for vascular stent biocompatibility improvement.

Nowadays, vascular stents are commonly used to treat cardiovascular diseases. This article focuses on the influence of nitrogen doping of titanium dioxide thin films, utilized for coating metallic stents to improve their biological properties and biocompatibility. The hereby-investigated titanium oxide thin films are fabricated by magnetron sputtering in a reactive gas atmosphere consisting of argon and oxygen in the first case and argon, nitrogen and oxygen in the second case. Control of the nitrogen and oxygen gas flow rates, and hence their mixing ratios, allows adjustment of the nitrogen-doping level within the titanium dioxide thin films. A correlation of the thin film internal structure on the in vitro behavior of human mesenchymal stem cells derived from adipose tissue is hereby demonstrated. Different nitrogen doping levels affect the surface energy, the wettability, the cell adhesion and thus the cellular proliferation on top of the thin films. The surface colonization of cells on titanium dioxide thin films decreases up to a nitrogen-doping level of âˆ¼ 3.75 at.%, which is associated with a decreasing polar component of the surface energy. For non-doped titanium dioxide thin films, a weak chondrogenesis of adult human adipose-derived mesenchymal stem cells with lower chondrogenic differentiation compared to glass is observed. An increasing nitrogen-doping level leads to linear increase in the chondrogenic differentiation rate, which is comparable to the control value of uncoated glass. Other investigated differentiated cell types do not display this behavior.

Recent Advances in Manufacturing Innovative Stents.

Cardiovascular diseases are the most distributed cause of death worldwide. Stenting of arteries as a percutaneous transluminal angioplasty procedure became a promising minimally invasive therapy based on re-opening narrowed arteries by stent insertion. In order to improve and optimize this method, many research groups are focusing on designing new or improving existent stents. Since the beginning of the stent development in 1986, starting with bare-metal stents (BMS), these devices have been continuously enhanced by applying new materials, developing stent coatings based on inorganic and organic compounds including drugs, nanoparticles or biological components such as genes and cells, as well as adapting stent designs with different fabrication technologies. Drug eluting stents (DES) have been developed to overcome the main shortcomings of BMS or coated stents. Coatings are mainly applied to control biocompatibility, degradation rate, protein adsorption, and allow adequate endothelialization in order to ensure better clinical outcome of BMS, reducing restenosis and thrombosis. As coating materials (i) organic polymers: polyurethanes, poly(ε-caprolactone), styrene-b-isobutylene-b-styrene, polyhydroxybutyrates, poly(lactide-co-glycolide), and phosphoryl choline; (ii) biological components: vascular endothelial growth factor (VEGF) and anti-CD34 antibody and (iii) inorganic coatings: noble metals, wide class of oxides, nitrides, silicide and carbide, hydroxyapatite, diamond-like carbon, and others are used. DES were developed to reduce the tissue hyperplasia and in-stent restenosis utilizing antiproliferative substances like paclitaxel, limus (siro-, zotaro-, evero-, bio-, amphi-, tacro-limus), ABT-578, tyrphostin AGL-2043, genes, etc. The innovative solutions aim at overcoming the main limitations of the stent technology, such as in-stent restenosis and stent thrombosis, while maintaining the prime requirements on biocompatibility, biodegradability, and mechanical behavior. This paper provides an overview of the existing stent types, their functionality, materials, and manufacturing conditions demonstrating the still huge potential for the development of promising stent solutions.

Surface evaluation of titanium oxynitride coatings used for developing layered cardiovascular stents.

Stents are important medical devices used to increase the quality and life expectancy of patients with heart diseases and stroke, leading causes of death, worldwide. In order to minimize the risk of restenosis, different coating on bare metal stents (BMS) such as polymer coatings; titanium dioxide, titanium nitride or titanium oxynitride coatings; carbon coatings and others are used. The aim of this work was to develop novel stents coated with titanium oxynitride (TiOxNy) with optimal chemical, mechanical and biological properties having possibly good coverage rate of inner and outer stent surfaces. The improvement should be achieved by optimization and development of a magnetron sputtering deposition technology. The goal of the study is understanding of the existing potential for improvement of the deposition technology and the coating quality itself. For this study, different O2/N2 ratios, meaning 1/2, 1/5 and 1/10 (the ratios of reagent gasses are given for the values of mass flows into the chamber) has been selected. Stability in simulated body fluids, surface morphology and protein adsorption as well as preliminary cytotoxic behaviour of the samples on HUVEC cells has been analysed. SEM experiments have shown the potential in the improvement of coating-stent adhesion by all samples. TiOxNy 1:5 samples were found to have the lowest adsorption, the smoothest surface morphology and the smallest rate of salt deposition from simulated body fluids (SBFs). This kind of surface has been recommended for further optimization and application.