Excess TGF-β1 Drives Cardiac Mesenchymal Stromal Cells to a Pro-Fibrotic Commitment in Arrhythmogenic Cardiomyopathy

Arrhythmogenic Cardiomyopathy (ACM) is characterized by the replacement of the myocardium with fibrotic or fibro-fatty tissue and inflammatory infiltrates in the heart. To date, while ACM adipogenesis is a well-investigated differentiation program, ACM-related fibrosis remains a scientific gap of knowledge. In this study, we analyze the fibrotic process occurring during ACM pathogenesis focusing on the role of cardiac mesenchymal stromal cells (C-MSC) as a source of myofibroblasts. We performed the ex vivo studies on plasma and right ventricular endomyocardial bioptic samples collected from ACM patients and healthy control donors (HC). In vitro studies were performed on C-MSC isolated from endomyocardial biopsies of both groups. Our results revealed that circulating TGF-β1 levels are significantly higher in the ACM cohort than in HC. Accordingly, fibrotic markers are increased in ACM patient-derived cardiac biopsies compared to HC ones. This difference is not evident in isolated C-MSC. Nevertheless, ACM C-MSC are more responsive than HC ones to TGF-β1 treatment, in terms of pro-fibrotic differentiation and higher activation of the SMAD2/3 signaling pathway. These results provide the novel evidence that C-MSC are a source of myofibroblasts and participate in ACM fibrotic remodeling, being highly responsive to ACM-characteristic excess TGF-β1.     

Si-substituted hydroxyapatite nanopowders: Synthesis, thermal stability and sinterability

Synthetic hydroxyapatites incorporating small amounts of Si have shown improved biological performances in terms of enhanced bone apposition, bone in-growth and cell-mediated degradation.This paper reports a systematic investigation on Si-substituted hydroxyapatite (Si 1.40 wt%) nanopowders produced following two different conventional wet methodologies: (a) precipitation of Ca(NO₃)₂·4H₂O and (b) titration of Ca(OH)₂. The influence of the synthesis process on composition, thermal behaviour and sinterability of the resulting nanopowders is studied.Samples were characterised by electron microscopy, induced coupled plasma atomic emission spectroscopy, thermal analysis, infrared spectroscopy, N₂ adsorption measurements, X-ray diffraction and dilatometry. Semicrystalline Si-substituted hydroxyapatite powders made up of needle-like nanoparticles were obtained, the specific surface area ranged between 84 and 110 m²/g. Pure and Si-substituted hydroxyapatite nanopowders derived from Ca(NO₃)₂·4H₂O decomposed around 1000 °C. Si-substituted hydroxyapatite nanopowders obtained from Ca(OH)₂ were thermally stable up to 1200 °C and showed a distinct decreased thermal stability with respect to the homologous pure sample. Si-substituted hydroxyapatites exhibited higher sintering temperature and increased total shrinkage with respect to pure powders. Nanostructured dense ceramics were obtained by sintering at 1100 °C Si-substituted hydroxyapatites derived from Ca(OH)₂.     

Dynamic Antifouling of Catalytic Pores Armed with Oxygenic Polyoxometalates

A novel stimuli‐responsive strategy against the irreversible fouling of porous materials and surfaces is presented herein. This is based on the molecular design of catalytic pore walls that foster a chemo‐mechanical, self‐cleaning behavior under neutral pH and mild conditions of pressure and temperature. This approach builds on bioinspired remediation mechanisms involving natural catalase enzymes for H₂O₂ dismutation and endogenous oxygen production. It is thus demonstrated that a very efficient antifouling activity is observed when the material pores are armed with oxygen evolving catalysts that are known to liberate nascent oxygen gas when exposed to H₂O₂ as chemical trigger. To this aim, the catalase‐like behavior of the tetra‐ruthenium substituted polyoxometalate (Ru₄(SiW₁₀)₂), has been exploited for in‐pore oxygen evolution so to induce an active fluid mixing and the displacement of foulant particles. The present study includes the fabrication of hybrid polymeric films with porous architecture embedding Ru₄(SiW₁₀)₂ as artificial catalase to guarantee the material self‐defense against pore occlusion and oxidative damage with aqueous H₂O₂ as mild chemical effector. The self‐catalytic “in‐pore” remediation is readily applied to various materials/interfaces with porous texture and high surface area with the aim to provide long‐lasting functional performances.     

The Design Guidelines (DGLs), a knowledge-based system for industrial design developed accordingly to ISO-GPS (Geometrical Product Specifications) concepts

Product design and optimisation today involves so many fields of expertise, many of which are in rapid evolution, that it can be very difficult for the designer to manage them. This paper describes the development of the DGLs (Design Guidelines), a knowledge-based tool that could be of great help to designers and engineers in modifying their products to get compatibility with different manufacturing and verification technologies. The current release of the DGLs, heavily influenced by the adoption of some ISO-GPS (Geometrical Product Specification) concepts, has been validated using the Rapid Prototyping technique called FDM (Fluid Deposition Modelling) and the CMM (Coordinate Measuring Machine) verification technique.     

Bottom Effect in Atomic Force Microscopy Nanomechanics

In this work, the influence of the rigid substrate on the determination of the sample Young's modulus, the so‐called bottom‐effect artifact, is demonstrated by an atomic force microscopy force‐spectroscopy experiment. The nanomechanical properties of a one‐component supported lipid membrane (SLM) exhibiting areas of two different thicknesses are studied: While a standard contact mechanics model (Sneddon) provides two different elastic moduli for these two morphologies, it is shown that Garcia's bottom‐effect artifact correction yields a unique value, as expected for an intrinsic material property. Remarkably, it is demonstrated that the ratio between the contact radius (and not only the indentation) and the sample thickness is the key parameter addressing the relevance of the bottom‐effect artifact. The experimental results are validated by finite element method simulations providing a solid support to Garcia's theory. The amphiphilic nature of the investigated material is representative of several kinds of lipids, suggesting that the results have far reaching implications for determining the correct Young's modulus of SLMs. The generality of Garcia's bottom‐effect artifact correction allows its application to every kind of supported soft film.     

Stable Non‐Covalent Large Area Patterning of Inert Teflon‐AF Surface: A New Approach to Multiscale Cell Guidance

Micro‐ and nano‐patterning of cell adhesion proteins is demonstrated to direct the growth of neural cells, viz. human neuroblastoma SHSY5Y, at precise positions on a strongly antifouling substrate of technolological interest. We adopt a soft‐lithographic approach with oxygen plasma modified PDMS stamps to pattern human laminin on Teflon‐AF films. These patterns are based on the interplay of capillary forces within the stamp and non‐covalent intermolecular and surface interactions. Remarkably, they remain stable for several days upon cell culture conditions. The fabrication of substrates with adjacent antifouling and adhesion‐promoting regions allows us to reach absolute spatial control in the positioning of neuroblastoma cells on the Teflon‐AF films. This patterning approach of a technologically‐relevant substrate can be of interest in tissue engineering and biosensing.     

High-Yield Separation of Extracellular Vesicles Using Programmable Zwitterionic Coacervates

Programmable coacervates based on zwitterionic polymers are designed as dynamic materials for ion exchange bioseparation. These coacervates are proposed as promising materials for the purification of soft nanoparticles such as liposomes and extracellular vesicles (EVs). It is shown that the stimulus-responsiveness of the coacervates and the recruitment of desired molecules can be independently programmed by polymer design. Moreover, the polymeric coacervates can recruit and release intact liposomes, human EVs, and nanoalgosomes in high yields and separate vesicles from different types of impurities, including proteins and nucleic acids. This approach combines the speed and simplicity of precipitation methods and the programmability of chromatography with the gentleness of aqueous two-phase separation, thereby guaranteeing product stability. This material represents a promising alternative for providing a low-shear, gentle, and selective purification method for EVs.     

A densification equation derived from the stress-deformation analysis of uniaxial cold compaction of metal powder mixes

A new densification equation for uniaxial cold compaction of four low alloy steel powders was determined from the deformation vs. mean axial stress correlation. Both deformation and stress are averaged along the height of the powder column. A power law relation, with two parameters representing the plasticity and the inverse of the resistance to deformation (densification) of the powder mix, respectively, fits the curves that are divided in two steps, distinguished by the prevailingdeformation/densification mechanism (rearrangement or plastic deformation).

Densification of the four powder mixes is greatly affected by the starting density in the die cavity, while the chemical composition of the base iron powder has a less significant effect.     

Stress-based performance evaluation of osseointegrated dental implants by finite-element simulation

In this paper biomechanical interaction between osseointegrated dental implants and bone is numerically investigated through 3D linearly elastic finite-element analyses, when static functional loads occur. Influence of some mechanical and geometrical parameters on bone stress distribution is highlighted and risk indicators relevant to critical overloading of bone are introduced. Insertions both in mandibular and maxillary molar segments are analyzed, taking into account different crestal bone loss configurations. Stress-based performances of five commercially-available dental implants are evaluated, demonstrating as the optimal choice of an endosseous implant is strongly affected by a number of shape parameters as well as by anatomy and mechanical properties of the site of placement. Moreover, effectiveness of some double-implant devices is addressed. The first one is relevant to a partially edentulous arch restoration, whereas other applications regard single-tooth restorations based on non-conventional endosteal mini-implants. Starting from computer tomography images and real devices, numerical models have been generated through a parametric algorithm based on a fully 3D approach. Furthermore, effectiveness and accuracy of finite-element simulations have been validated by means of a detailed convergence analysis.     

Evaluating the Potential of Quarry Lakes for Supplemental Irrigation

Population growth coupled with industrialization, increasing effects of climate change, and increasingly stringent water management regulations regarding the conservation of aquatic life are resulting in previously unknown agricultural water shortages in Padana Valley, Italy. To mitigate water shortage, it was recently proposed to use the water stored into numerous quarries of gravel material. Because quarry lakes are mostly located in the proximity of watercourses, aquifer drawdown induced by pumping can affect flow in nearby streams. The evaluation of the potential of quarry lakes for supplemental irrigation has to face stream depletion that is crucial from the perspective of the legal rights of the downstream users and ecosystem sustainability. The work presented in this paper investigates the potential of a quarry lake in Padana Valley to sustain irrigated crop water requirement during shortage periods. A simple and quite inexpensive technique for assessing streambed conductance based on streambed temperature measurements is presented. The results show that quarry lakes may be a promising alternative resource for supplemental irrigation during shortage periods, even when a watercourse is present in the surrounding area.