Characterization of Tannic Acid-Coated AZ31 Mg Alloy for Biomedical Application and Comparison with AZ91.

Magnesium alloys are promising materials for bioresorbable implants that will improve patient life and reduce healthcare costs. However, their clinical use is prevented by the rapid degradation and corrosion of magnesium, which leads to a fast loss of mechanical strength and the formation of by-products that can trigger tissue inflammation. Here, a tannic acid coating is proposed to control the degradation of AZ31 and AZ91 alloys, starting from a previous study by the authors on AZ91. The coatings on the two materials were characterized both by the chemical (EDS, FTIR, XPS) and the morphological (SEM, confocal profilometry) point of view. Static degradation tests in PBS and electrochemical measurements in different solutions showed that the protective performances of the tannic acid coatings are strongly affected by the presence of cracks. The presence of fractures in the protective layer generates galvanic couples between the coating scales and the metal, worsening the corrosion resistance. Although degradation control was not achieved, useful insights on the degradation mechanisms of coated Mg surfaces were obtained, as well as key points for future studies: it resulted that the absence of cracks in protective coatings is of uttermost importance for novel biodegradable implants with proper degradation kinetics.

Advances in In Vitro Blood-Air Barrier Models and the Use of Nanoparticles in COVID-19 Research.

Respiratory infections caused by coronaviruses (CoVs) have become a major public health concern in the past two decades as revealed by the emergence of SARS-CoV in 2002, MERS-CoV in 2012, and SARS-CoV-2 in 2019. The most severe clinical phenotypes commonly arise from exacerbation of immune response following the infection of alveolar epithelial cells localized at the pulmonary blood-air barrier. Preclinical rodent models do not adequately represent the essential genetic properties of the barrier, thus necessitating the use of humanized transgenic models. However, existing monolayer cell culture models have so far been unable to mimic the complex lung microenvironment. In this respect, air-liquid interface models, tissue engineered models, and organ-on-a-chip systems, which aim to better imitate the infection site microenvironment and microphysiology, are being developed to replace the commonly used monolayer cell culture models, and their use is becoming more widespread every day. On the contrary, studies on the development of nanoparticles (NPs) that mimic respiratory viruses, and those NPs used in therapy are progressing rapidly. The first part of this review describes in vitro models that mimic the blood-air barrier, the tissue interface that plays a central role in COVID-19 progression. In the second part of the review, NPs mimicking the virus and/or designed to carry therapeutic agents are explained and exemplified.

Nanodiamond Decorated PEO Oxide Coatings on NiTi Alloy.

Cardiovascular diseases (CVDs) remain a leading cause of death in the European population, primarily attributed to atherosclerosis and subsequent complications. Although statin drugs effectively prevent atherosclerosis, they fail to reduce plaque size and vascular stenosis. Bare metal stents (BMS) have shown promise in acute coronary disease treatment but are associated with restenosis in the stent. Drug-eluting stents (DES) have improved restenosis rates but present long-term complications. To overcome these limitations, nanomaterial-based modifications of the stent surfaces have been explored. This study focuses on the incorporation of detonation nanodiamonds (NDs) into a plasma electrolytic oxidation (PEO) coating on nitinol stents to enhance their performance. The functionalized ND showed a high surface-to-volume ratio and was incorporated into the oxide layer to mimic high-density lipoproteins (HDL) for reverse cholesterol transport (RCT). We provide substantial characterization of DND, including stability in two media (acetone and water), Fourier transmission infrared spectroscopy, and nanoparticle tracking analysis. The characterization of the modified ND revealed successful functionalization and adequate suspension stability. Scanning electron microscopy with EDX demonstrated successful incorporation of DND into the ceramic layer, but the formation of a porous surface is possible only in the high-voltage PEO. The biological assessment demonstrated the biocompatibility of the decorated nitinol surface with enhanced cell adhesion and proliferation. This study presents a novel approach to improving the performance of nitinol stents using ND-based surface modifications, providing a promising avenue for cardiovascular disease.

Cleaning of LTCC, PEN, and PCB Au electrodes towards reliable electrochemical measurements.

Surface cleaning of the working electrode has a key role in improved electrochemical and physicochemical properties of the biosensors. Herein, chemical oxidation in piranha, chemical cleaning in potassium hydroxide-hydrogen peroxide, combined (electro-) chemical alkaline treatment, and potential cycling in sulfuric acid were applied to gold finish electrode surfaces deposited onto three different substrates; low temperature co-fired ceramics (LTCC), polyethylene naphthalate (PEN), and polyimide (PI), using three different deposition technologies; screen printing, inkjet printing, and electroplating (printed circuit board technology, PCB) accordingly. The effects of the (electro-) chemical treatments on the gold content and electrochemical responses of LTCC, PEN, and PCB applicable for aptamer-based sensors are discussed. In order to assess the gold surface and to compare the efficiency of the respective cleaning procedures; cyclic voltammetry (CV), electrochemical impedance spectroscopy (EIS), X-ray photoelectron spectroscopy (XPS), and scanning electron microscopy (SEM) were employed. LTCC sensors electrochemically cycled in sulfuric acid resulted in the most gold content on the electrode surface, the lowest peak potential difference, and the highest charge transfer ability. While, for PEN, the highest elemental gold and the lowest peak-to-peak separation were achieved by a combined (electro-) chemical alkaline treatment. Gold content and electrochemical characteristics on the PCB surface with extremely thin gold layer could be slightly optimized with the chemical cleaning in KOH + H2O2. The proposed cleaning procedures might be generally applied to various kinds of Au electrodes fabricated with the same conditions comparable with those are introduced in this study.

Effect of Chemically Modified Carbon-Coated Iron Nanoparticles on the Structure of Human Atherosclerotic Plaques Ex Vivo and on Adipose Tissue in Chronic Experiment In Vivo.

The high mortality rate caused by atherosclerosis makes it necessary to constantly search for new and better treatments. In previous reports, chemically modified carbon-coated iron nanoparticles (Fe@C NPs) have been demonstrated a high biocompatibility and promising anti-plaque properties. To further investigate these effects, the interaction of these nanoparticles with the adipose tissue of Wistar rats (in vivo) and human atherosclerotic plaques (ex vivo) was studied. For the in vivo study, cobalt-chromium (CoCr) alloy tubes, which are used for coronary stent manufacturing, were prepared with a coating of polylactic acid (PLA) which contained either modified or non-modified Fe@C NPs in a 5% by weight concentration. The tubes were implanted into an area of subcutaneous fat in Wistar rats, where changes in the histological structure and functional properties of the surrounding tissue were observed in the case of coatings modified with Fe@C NPs. For the ex vivo study, freshly explanted human atherosclerotic plaques were treated in the physiological solution with doses of modified Fe@C NPs, with mass equal to 5% or 25% relative to the plaques. This treatment resulted in the release of cholesterol-like compounds from the surface of the plaques into the solution, thus proving a pronounced destructive effect on the plaque structure. Chemically modified Fe@C NPs, when used as an anti-atherosclerosis agent, were able to activate the activity of macrophages, which could lead to the destruction of atherosclerotic plaques structures. These findings could prove the fabrication of next-generation vascular stents with built-in anti-atherosclerotic agents.

Chemically Modified Biomimetic Carbon-Coated Iron Nanoparticles for Stent Coatings: In Vitro Cytocompatibility and In Vivo Structural Changes in Human Atherosclerotic Plaques.

Atherosclerosis, a systematic degenerative disease related to the buildup of plaques in human vessels, remains the major cause of morbidity in the field of cardiovascular health problems, which are the number one cause of death globally. Novel atheroprotective HDL-mimicking chemically modified carbon-coated iron nanoparticles (Fe@C NPs) were produced by gas-phase synthesis and modified with organic functional groups of a lipophilic nature. Modified and non-modified Fe@C NPs, immobilized with polycaprolactone on stainless steel, showed high cytocompatibility in human endothelial cell culture. Furthermore, after ex vivo treatment of native atherosclerotic plaques obtained during open carotid endarterectomy surgery, Fe@C NPs penetrated the inner structures and caused structural changes of atherosclerotic plaques, depending on the period of implantation in Wistar rats, serving as a natural bioreactor. The high biocompatibility of the Fe@C NPs shows great potential in the treatment of atherosclerosis disease as an active substance of stent coatings to prevent restenosis and the formation of atherosclerotic plaques.

Determination of the Entire Stent Surface Area by a New Analytical Method.

Stenting is a widely used treatment procedure for coronary artery disease around the world. Stents have a complex geometry, which makes the characterization of their corrosion difficult due to the absence of a mathematical model to calculate the entire stent surface area (ESSA). Therefore, corrosion experiments with stents are mostly based on qualitative analysis. Additionally, the quantitative analysis of corrosion is conducted with simpler samples made of stent material instead of stents, in most cases. At present, several methods are available to calculate the stent outer surface area (SOSA), whereas no model exists for the calculation of the ESSA. This paper presents a novel mathematical model for the calculation of the ESSA using the SOSA as one of the main parameters. The ESSA of seven magnesium alloy stents (MeKo Laser Material Processing GmbH, Sarstedt, Germany) were calculated using the developed model. The calculated SOSA and ESSA for all stents are 33.34%(±0.26%) and 111.86 mm (±0.85 mm), respectively. The model is validated by micro-computed tomography (micro-CT), with a difference of 12.34% (±0.46%). The value of corrosion rates calculated using the ESSA computed with the developed model will be 12.34% (±0.46%) less than that of using ESSA obtained by micro-CT.

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.

Treatment with bisphosphonates to mitigate calcification of elastin-containing bioprosthetic materials.

This study evaluated the ability of bisphosphonates (BPAs) of different molecular structures to mitigate the calcification of porcine aortic wall (PAW) and bovine jugular vein wall (BJVW). Tissues cross-linked with glutaraldehyde (GA) or diepoxide (DE) were modified with pamidronic acid (PAM), alendronic acid (ALE), neridronic acid (NER) (type 1 BPAs); 2-(2'-carboxyethylamino)ethylidene-1,1-bisphosphonic acid (CEABA), 2-(5-carboxypentylamino)ethylidene-1,1-bisphosphonic acid (CPABA) (type 2); and zoledronic acid (ZOL) (type 3). After implanting the tissue samples subcutaneously in 100 rats, calcification was examined using atomic absorption spectrophotometry (60-day explants) and light microscopy after von Kossa staining (10- and 30-day explants). The calcium contents in GA-BJVW and GA- and DE-PAW increased up to 100-120 mg/g after 60 days, while being 3 times lower in DE-BJVW. In modified and nonmodified PAW samples, calcium phosphates appeared by day 10 and were associated with elastic fibers and devitalized cellular elements. In all groups of BJVW samples, mineralization began in elastic fibers near the subendothelial layer. In addition, calcified collagen was found in the GA-BJVW samples. Minimal calcification was found in GA-PAW treated with type 1 BPAs and CEABA. For DE-PAW and GA-BJVW, the calcium level significantly decreased with PAM and CEABA. Meanwhile, ALE and NER were effective for DE-BJVW.

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.