Magnetic field dynamic strategies for the improved control of the angiogenic effect of mesenchymal stromal cells

project PTDC/EDM-EDM/30828/2017 SFRH/BD/114043/2015 co-financed by the ERDF under the PT2020 Partnership Agreement (POVI-01-0145-FEDER-007265), as well as from POR Lisboa 2020 grant PRECISE (Project N. 16394). Publisher Copyright: © 2021 by the authors. Licensee MDPI, Basel, Switzerland.This work shows the ability to remotely control the paracrine performance of mesenchymal stromal cells (MSCs) in producing an angiogenesis key molecule, vascular endothelial growth factor (VEGF-A), by modulation of an external magnetic field. This work compares for the first time the application of static and dynamic magnetic fields in angiogenesis in vitro model, exploring the effect of magnetic field intensity and dynamic regimes on the VEGF-A secretion potential of MSCs. Tissue scaffolds of gelatin doped with iron oxide nanoparticles (MNPs) were used as a platform for MSC proliferation. Dynamic magnetic field regimes were imposed by cyclic variation of the magnetic field intensity in different frequencies. The effect of the magnetic field intensity on cell behavior showed that higher intensity of 0.45 T was associated with increased cell death and a poor angiogenic effect. It was observed that static and dynamic magnetic stimulation with higher frequencies led to improved angiogenic performance on endothelial cells in comparison with a lower frequency regime. This work showed the possibility to control VEGF-A secretion by MSCs through modulation of the magnetic field, offering attractive perspectives of a non-invasive therapeutic option for several diseases by revascularizing damaged tissues or inhibiting metastasis formation during cancer progression.publishersversionpublishe

Accessing gelling ability of vegetable proteins using rheological and fluorescence techniques

This work aims to present a comprehensive study about the macroscopic characteristics of globular vegetable proteins, in terms of their gelling ability, by understanding their molecular behaviour, when submitted to a thermal gelling process. The gels of soy, pea and lupin proteins were characterized by rheological techniques. Gelation kinetics, mechanical spectra, as well as the texture of these gels were analyzed and compared. Additionally, capillary viscometry, steady-state fluorescence and fluorescence anisotropy were used to monitor the structural changes induced by the thermal denaturation, which constitutes the main condition for the formation of a gel structure. Based on these techniques it was possible to establish a relationship between the gelling ability of each protein isolate and their structural resistance to thermal unfolding, enabling us to explain the weakest and the strongest gelling ability observed for lupin and soy proteins isolates, respectivel

Design of alumina monoliths by emulsion-gel casting: understanding the monolith structure from a rheological approach

Multimodal porous cellular alumina structures (monoliths) were prepared by an emulsion-gel casting technique using eco-friendly and inexpensive lipids such as corn oil, castor oil, margarine and their mixtures as the dispersed phase. The monoliths obtained showed good mechanical stability, exhibiting compressive strengths in the range of 8–50 N·mm−2. Mercury intrusion porosimetry analysis showed that the monoliths produced presented porosities ranging from 28% to 60% and average pore sizes within 0.2–3.2 μm. The formation of the porous networks was interpreted based on combined droplet coalescence, flocculation and Ostwald ripening effects. The presence of such effects along the emulsion storage time led to changes in their viscoelastic and morphological properties, which were found to correlate with structural descriptors of monoliths after sintering (e.g. average pore sizes and porosity). These correlations open up the possibility to anticipate the final structure of the monoliths and adjust emulsion-gel conditions to produce customized cellular structures with fine-tuned porosities and pore sizes, envisaging their application in membrane processes or chromatography.publishe

Design of Blood Vessel Models using Magnetic-Responsive Vascular Platforms

The design of physiologically relevant blood vessel in vitro models has been impaired by the difficulty to reproduce the complex architecture of native blood vessels and the mechanisms mediating key cellular functions within miniaturized perfusable systems. Aiming to simulate blood vessel walls, in this work innovative 2D platforms are designed and patterned with magnetic-responsive gelatin for enabling in situ co-culture of mesenchymal stromal cells (MSCs) and human umbilical vein endothelial cells (HUVECs) within confined compartments. The performance of the 2D chips is evaluated based on HUVECs migration, adherence, and angiogenic behavior (proliferation and sprouting), as well as production of Endothelin-1 (endothelium marker), and compared with the results of 3D single channel models, designed to mimic the morphology of native arteries and veins. The 2D chips obtain better cell adhesion and angiogenic performance, which is attributed to flow profiles and VEGF concentration gradients. Magnetic stimulation is then used as a novel strategy to increase cell sprouting and endothelization ≈1.5 times above the control condition. These bio-inspired devices advance the exploration of magnetism for a finer convergence to the native vascular conditions in vitro and improved modulation of angiogenesis, showing promising contributions to the development of sophisticated therapeutics for vascular ischemia-related diseases.</p

Magnetic blood vessel devices as vascularization models

Mimicking the vascularization of the native tissue microenvironment is a widely studied yet still challenging field of research. In this work, artificial blood vessels were fabricated in novel scaffolds made of gelatin and magnetic nanoparticles. The constructs, in 2D (microfluidic chips) and 3D (macro-molded tubing models), were designed to enable cell proliferation, migration, and angiogenic sprouting using co-cultures of MSCs (mesenchymal stromal cells) and HUVECs (human umbilical vein endothelial cells). As the key innovation of this study, magnetic actuation was used to promote stimulant-free angiogenesis by successfully inducing the formation of microvessel matrix, thus contributing to the vascularization of the blood vessel models.</p

Magnetic blood vessel devices as vascularization models

Mimicking the vascularization of the native tissue microenvironment is a widely studied yet still challenging field of research. In this work, artificial blood vessels were fabricated in novel scaffolds made of gelatin and magnetic nanoparticles. The constructs, in 2D (microfluidic chips) and 3D (macro-molded tubing models), were designed to enable cell proliferation, migration, and angiogenic sprouting using co-cultures of MSCs (mesenchymal stromal cells) and HUVECs (human umbilical vein endothelial cells). As the key innovation of this study, magnetic actuation was used to promote stimulant-free angiogenesis by successfully inducing the formation of microvessel matrix, thus contributing to the vascularization of the blood vessel models.</p

Flexible design of cellular Al2TiO5 and Al2TiO5-Al2O3 composite monoliths by reactive firing

Cellular Al2TiO5 and Al2TiO5 – Al2O3 composite ceramics were obtained by emulsification of liquid paraffin in aqueous suspensions of mixed TiO2 + Al2O3 powders, with subsequent burnout of the organic phase and 2-step reactive firing at high temperatures. The reactants ratio and paraffin to suspension volume ratio were used as primary parameters to control the phase composition and relevant microstructural features, while firing conditions were also adjusted for greater flexibility in designing Al2TiO5-based cellular materials. Taguchi experimental planning was used to assess the relevant impacts of 2-step firing parameters on phase composition and porosity, characterized by detailed XRD/SEM/EDS studies. The results emphasized the positive effects of Al2O3 excess in Al2TiO5 – Al2O3 composite ceramics on stabilization of the Al2TiO5 phase and also for flexible design of cellular materials with controlled porosity and phase distributions. Analysis of correlation matrixes identified the 2-step firing parameters with greatest impact on the porosity and phase composition, and these trends were confirmed by multivariate linear regression. The observed trends indicated significant differences in reactivity and densification mechanisms between compositions with nominal Al2TiO5 stoichiometry and composite materials. These differences were most obvious for samples with significant residual fractions of unreacted titania