Analytical and Numerical Models of Thermoplastics: A Review Aimed to Pellet Extrusion-Based Additive Manufacturing.

Recent developments in additive manufacturing have moved towards a new trend in material extrusion processes (ISO/ASTM 52910:2018), dealing with the direct extrusion of thermoplastic and composite material from pellets. This growing interest is driven by the reduction of costs, environmental impact, energy consumption, and the possibility to increase the range of printable materials. Pellet additive manufacturing (PAM) can cover the same applications as fused filament fabrication (FFF), and in addition, can lead to scale towards larger workspaces that cannot be covered by FFF, due to the limited diameters of standard filaments. In the first case, the process is known as micro- or mini-extrusion (MiE) in the literature, in the second case the expression big area additive manufacturing (BAAM) is very common. Several models are available in literature regarding filament extrusion, while there is a lack of modeling of the extrusion dynamics in PAM. Physical and chemical phenomena involved in PAM have high overlap with those characterizing injection molding (IM). Therefore, a systematic study of IM literature can lead to a selection of the most promising models for PAM, both for lower (MiE) and larger (BAAM) extruder dimensions. The models concerning the IM process have been reviewed with this aim: the extraction of information useful for the development of codes able to predict thermo-fluid dynamics performances of PAM extruders.

Fused Filament Fabrication (FFF) for Manufacturing of Microfluidic Micromixers: An Experimental Study on the Effect of Process Variables in Printed Microfluidic Micromixers.

The need for accessible and inexpensive microfluidic devices requires new manufacturing methods and materials as a replacement for traditional soft lithography and polydimethylsiloxane (PDMS). Recently, with the advent of modern additive manufacturing (AM) techniques, 3D printing has attracted attention for its use in the fabrication of microfluidic devices and due to its automated, assembly-free 3D fabrication, rapidly decreasing cost, and fast-improving resolution and throughput. Here, fused filament fabrication (FFF) 3D printing was used to create microfluidic micromixers and enhance the mixing process, which has been identified as a challenge in microfluidic devices. A design of experiment (DoE) was performed on the effects of studied parameters in devices that were printed by FFF. The results of the colorimetric approach showed the effects of different parameters on the mixing process and on the enhancement of the mixing performance in printed devices. The presence of the geometrical features on the microchannels can act as ridges due to the nature of the FFF process. In comparison to passive and active methods, no complexity was added in the fabrication process, and the ridges are an inherent property of the FFF process.

Tandem Mn-I Exchange and Homocoupling Processes Mediated by a Synergistically Operative Lithium Manganate.

Pairing lithium and manganese(II) to form lithium manganate [Li2 Mn(CH2 SiMe3 )4 ] enables the efficient direct Mn-I exchange of aryliodides, affording transient (aryl)lithium manganate intermediates which in turn undergo spontaneous C-C homocoupling at room temperature to furnish symmetrical (bis)aryls in good yields under mild reaction conditions. The combination of EPR with X-ray crystallographic studies has revealed the mixed Li/Mn constitution of the organometallic intermediates involved in these reactions, including the homocoupling step which had previously been thought to occur via a single-metal Mn aryl species. These studies show Li and Mn working together in a synergistic manner to facilitate both the Mn-I exchange and the C-C bond-forming steps. Both steps are carefully synchronized, with the concomitant generation of the alkyliodide ICH2 SiMe3 during the Mn-I exchange being essential to the aryl homocoupling process, wherein it serves as an in situ generated oxidant.

Effects of mitral chordae tendineae on the flow in the left heart ventricle.

In this paper a computational model for the ventricular flow with a mitral valve and modeled chordae tendineae is presented. The results are compared with an analogous case in which the chordae are not included and their presence is replaced by kinematic boundary conditions. The problem is studied using direct numerical simulation of the Navier-Stokes equations, two-way coupled with a structural solver for the ventricle and mitral valve dynamics. An experimental validation of the model is performed by a comparison of the results with a companion dedicated experiment. It is found that the inclusion of the chordae tendineae makes the model self-consistent thus avoiding the use of ad hoc kinematic constraints to mimic their effect. In this way it is possible to simulate the correct system dynamics without user-defined parameters. More in detail, the results have shown that the mitral valve dynamics can be described also without chordae with the help of ad hoc kinematic constrains, whereas the changes produced in the intra-ventricular flow need the explicit consideration of the chordae in the model. On the other hand, the computational load increases owing to the presence of additional structures that, being thin filaments, are also demanding for the spatial resolution requirements. Since the presence of the chordae tendineae produces only specific differences in the overall flow structure, we conclude that their explicit modeling should be limited to those cases in which their presence is unavoidable.

Structural and Mechanistic Insights into s-Block Bimetallic Catalysis: Sodium Magnesiate-Catalyzed Guanylation of Amines.

To advance the catalytic applications of s-block mixed-metal complexes, sodium magnesiate [NaMg(CH2 SiMe3 )3 ] (1) is reported as an efficient precatalyst for the guanylation of a variety of anilines and secondary amines with carbodiimides. First examples of hydrophosphination of carbodiimides by using a Mg catalyst are also described. The catalytic ability of the mixed-metal system is much greater than that of its homometallic components [NaCH2 SiMe3 ] and [Mg(CH2 SiMe3 )2 ]. Stoichiometric studies suggest that magnesiate amido and guanidinate complexes are intermediates in these catalytic routes. Reactivity and kinetic studies imply that these guanylation reactions occur via (tris)amide intermediates that react with carbodiiimides in insertion steps. The rate law for the guanylation of N,N'-diisopropylcarbodiimide with 4-tert-butylaniline catalyzed by 1 is first order with respect to [amine], [carbodiimide], and [catalyst], and the reaction shows a large kinetic isotopic effect, which is consistent with an amine-assisted rate-determining carbodiimide insertion transition state. Studies to assess the effect of sodium in these transformations denote a secondary role with little involvement in the catalytic cycle.

A strain-based model for mechanical hemolysis based on a coarse-grained red blood cell model.

Mechanical hemolysis is a major concern in the design of cardiovascular devices, such as prosthetic heart valves and ventricular assist devices. The primary cause of mechanical hemolysis is the impact of the device on the local blood flow, which exposes blood elements to non-physiologic conditions. The majority of existing hemolysis models correlate red blood cell (RBC) damage to the imposed fluid shear stress and exposure time. Only recently more realistic, strain-based models have been proposed, where the RBC's response to the imposed hydrodynamic loading is accounted for. In the present work we extend strain-based models by introducing a high-fidelity representation of RBCs, which is based on existing coarse-grained particle dynamics approach. We report a series of numerical experiments in simple shear flows of increasing complexity, to illuminate the basic differences between existing models and establish their accuracy in comparison to the high-fidelity RBC approach. We also consider a practical configuration, where the flow through an artificial heart valve is computed. Our results shed light on the strengths and weaknesses of each approach and identify the key gaps that should be addressed in the development of new models.

Potassium-alkyl magnesiates: synthesis, structures and Mg-H exchange applications of aromatic and heterocyclic substrates.

Using structurally well-defined dipotassium-tetra(alkyl)magnesiates, a new straightforward methodology to promote regioselective Mg-H exchange reactions of a wide range of aromatic and heteroaromatic substrates is disclosed. Contacted ion pair intermediates are likely to be involved, with K being the key to facilitate the magnesiation processes.

siRNA-chitosan complexes in poly(lactic-co-glycolic acid) nanoparticles for the silencing of aquaporin-1 in cancer cells.

A large number of studies document the strong expression of aquaporin-1 (AQP1) in tumor microvessels and correlate this aberrant expression with higher metastatic potential and aggressiveness of the malignancy. Although small animal experiments have shown that the modulation of AQP1 expression can halt angiogenesis and induce tumor regression, effective and safe strategies for the tissue specific inhibition of AQP1 are still missing. Here, small interference RNA-chitosan complexes encapsulated in poly(lactic-co-glycolic acid) (PLGA) nanoparticles (NPs) are proposed for the intracellular delivery of siRNA molecules against AQP1. These NPs are coated with poly(vinyl alcohol) (PVA), to improve stability under physiological conditions, and demonstrate a diameter of 160 nm. The partial neutralization of the negatively charged siRNA molecules with the cationic chitosan enhances the loading by 5-fold, as compared to that of the free siRNA molecules, and allows one to modulate the release kinetics in the pH-dependent manner. At pH = 7.4, mimicking the conditions found in the systemic circulation, only the 40% of siRNA is released at 24 h post incubation; whereas at pH = 5.0, recreating the cell endosomal environment, all siRNA molecules are released in about 3 h. These NPs show no cytotoxicity on HeLa cells up to 72 h of incubation. In the same cells, transfected to overexpress AQP1, a silencing efficiency of 70% is achieved at 24 h post treatment with siRNA-loaded NPs. Confocal microscopy analysis of NP uptake demonstrates that siRNA molecules accumulate perinuclearly and in the nucleus. Given the stability, preferential release behavior, and well-known biocompatibility properties of PLGA nanostructures, these siRNA-loaded NPs hold potential for the efficient and safe in vivo silencing of AQPs via systemic administration.

Annular dilatation and loss of sino-tubular junction in aneurysmatic aorta: implications on leaflet quality at the time of surgery. A finite element study.

OBJECTIVES: In the belief that stress is the main determinant of leaflet quality deterioration, we sought to evaluate the effect of annular and/or sino-tubular junction dilatation on leaflet stress. A finite element computer-assisted stress analysis was used to model four different anatomic conditions and analyse the consequent stress pattern on the aortic valve. METHODS: Theoretical models of four aortic root configurations (normal, with dilated annulus, with loss of sino-tubular junction and with both dilatation simultaneously) were created with computer-aided design technique. The pattern of stress and strain was then analysed by means of finite elements analysis, when a uniform pressure of 100 mmHg was applied to the model. Analysis produced von Mises charts (colour-coded, computational, three-dimensional stress-pattern graphics) and bidimensional plots of compared stress on arc-linear line, which allowed direct comparison of stress in the four different conditions. RESULTS: Stresses both on the free margin and on the 'belly' of the leaflet rose from 0.28 MPa (normal conditions) to 0.32 MPa (+14%) in case of isolated dilatation of the sino-tubular junction, while increased to 0.42 MPa (+67%) in case of isolated annular dilatation, with no substantial difference whether sino-tubular junction dilatation was present or not. CONCLUSIONS: Annular dilatation is the key element determining an increased stress on aortic leaflets independently from an associated sino-tubular junction dilatation. The presence of annular dilatation associated with root aneurysm greatly decreases the chance of performing a valve sparing procedure without the need for additional manoeuvres on leaflet tissue. This information may lead to a refinement in the optimal surgical strategy.

The preferential targeting of the diseased microvasculature by disk-like particles.

Different classes of nanoparticles (NPs) have been developed for controlling and improving the systemic administration of therapeutic and contrast agents. Particle shape has been shown to be crucial in the vascular transport and adhesion of NPs. Here, we use mesoporous silicon non-spherical particles, of disk and rod shapes, ranging in size from 200nm to 1800nm. The fabrication process of the mesoporous particles is described in detail, and their transport and adhesion properties under flow are studied using a parallel plate flow chamber. Numerical simulations predict the hydrodynamic forces on the particles and help in interpreting their distinctive behaviors. Under microvascular flow conditions, for disk-like shape, 1000×400nm particles show maximum adhesion, whereas smaller (600×200nm) and larger (1800×600nm) particles adhere less by a factor of about two. Larger rods (1800×400nm) are observed to adhere at least 3 times more than smaller ones (1500×200nm). For particles of equal volumes, disks adhere about 2 times more than rods. Maximum adhesion for intermediate sized disks reflects the balance between adhesive interfacial interactions and hydrodynamic dislodging forces. In view of the growing evidence on vascular molecular heterogeneity, the present data suggests that thin disk-like particles could more effectively target the diseased microvasculature as compared to spheres and slender rods.