Modeling of Microneedle Arrays in Transdermal Drug Delivery Applications.

The use of computational tools for the development of technologies in fields such as medicine and engineering has facilitated the process of designing new components and devices for these areas. In this work, two proposals focused on a hollow microneedle array (MNA) for the administration of an analgesic drug are shown and evaluated by means of a computational fluid dynamics (CFD) simulation distributed in three stages. In the first stage, the behavior of lidocaine through the MNA was evaluated as a workflow. Then, the possible entry of the drug into the organism, which was established as a porous aqueous medium, was modeled. Finally, a joint simulation was performed to understand the general behavior in the interaction between the outflow of an MNA and the body to which lidocaine is administered. The input parameters to the simulation were set at a velocity of 0.05 m∙s-1, at a pressure of 2000 Pa, the dominant behavior was defined as laminar flow, and a resistive pressure at the inlet of 400 Pa. Our results indicate that the vertical flow exhibits a better fluid distribution across the MNAs and favorable infiltration behavior, representing better delivery of the analgesic to the skin capillaries.

Phonon Dominated Thermal Transport in Metallic Niobium Diselenide from First Principles Calculations.

Niobium diselenide (NbSe2) is a layered transition metal dichalcogenide material which possesses unique electrical and superconducting properties for future nanodevices. While the superconducting, electrical, and bulk thermal transport properties of NbSe2 have been widely studied, the in-plane thermal transport property of NbSe2, which is important for potential thermoelectric applications, has not been thoroughly investigated. In this report, we study the lattice in-plane thermal transport of 2D NbSe2 by solving the phonon Boltzmann transport equation with the help of the first principles calculation. The thermal conductivity obtained at room temperature is 12.3 W/mK. A detailed analysis shows that the transverse acoustic phonon dominates the lattice thermal transport, and an anomalously small portion of electron contribution to the total thermal conductivity is observed for this metallic phase. The results agree well with experimental measurements and provide detailed mode-by-mode thermal conductivity contribution from different phonon modes. This study can provide useful information for integrating NbSe2 in nanodevices where both electrical and thermal properties are critical, showing great potential for integrating monolayer NbSe2 to thermoelectric devices.

An inverse fitting strategy to determine the constrained mixture model parameters: application in patient-specific aorta.

The Constrained Mixture Model (CMM) is a novel approach to describe arterial wall mechanics, whose formulation is based on a referential physiological state. The CMM considers the arterial wall as a mixture of load-bearing constituents, each of them with characteristic mass fraction, material properties, and deposition stretch levels from its stress-free state to the in-vivo configuration. Although some reports of this model successfully assess its capabilities, they barely explore experimental approaches to model patient-specific scenarios. In this sense, we propose an iterative fitting procedure of numerical-experimental nature to determine material parameters and deposition stretch values. To this end, the model has been implemented in a finite element framework, and it is calibrated using reported experimental data of descending thoracic aorta. The main results obtained from the proposed procedure consist of a set of material parameters for each constituent. Moreover, a relationship between deposition stretches and residual strain measurements (opening angle and axial stretch) has been numerically proved, establishing a strong consistency between the model and experimental data.

Analysis of the geometrical influence of ring-opening samples on arterial circumferential residual stress reconstruction.

This work consists of analyzing the impact of geometrical features (thickness and curvature) on the estimation of circumferential residual stresses in arteries. For this purpose, a specific sample of lamb abdominal artery is chosen for analysis and, through computational tools based on Python libraries, the stress-free geometry is captured after the ring opening test. Numerical simulations are then used to reconstruct the sample in order to estimate the circumferential residual stresses. Then, four stress-free geometry models are analyzed: an ideal geometry, i.e., constant curvature and thickness; a constant curvature and variable thickness geometry; a variable curvature and constant thickness geometry; and a variable curvature and thickness geometry. The numerical results show that models perform well from a geometric point of view, where the most different feature was the closed outer perimeter that differs about 14% from the closed real sample. As far as residual stress is concerned, differences up to 198% were found in more realistic models taking a constant curvature and thickness model as reference. Thus, the analysis of a realistic geometry with highly variable curvature and thickness can introduce, compared to an idealized geometry, significant differences in the estimation of residual stresses. This could indicate that the characterization of arterial residual stresses is not sufficient when considering only the opening angle and, therefore, it is also necessary to incorporate more geometrical variables.

Hyperelastic and damage properties of the hypoxic aorta treated with Cinaciguat.

Chronic hypoxia during gestation and postnatal period induces pulmonary hypertension, aorta stiffening and vascular remodeling. In this study, we hypothesized that a postnatal treatment with Cinaciguat, a guanylate cyclase activator, may improve the vascular function by enhancing NO-sGC pathways that induce vasodilation. To assess this, we collected aortas from six lambs gestated, born and raised at 3600 masl. Half of these lambs received a Cinaciguat postnatal treatment, while the other half was used as control (vehicle). Uniaxial tension was applied on samples of each group of aortas (control and Cinaciguat-treated) through cyclic loading. The obtained stress-stretch curves were used to identify constitutive parameters of a hyperelastic damage model. These material constants allowed us to assess the softening/dissipation behavior and to characterize the treatment effects. Results showed that Cinaciguat has an effect on the damage behavior at large strains, altering the damage onset under uniaxial tension. We conclude that Cinaciguat, as a vasodilator, can prevent the very early effects of vascular remodeling caused by perinatal hypoxia, and improve the aortic-tissue damage properties of hypoxic lambs.

Characterization of the active response of a guinea pig carotid artery.

This work presents a characterization of the active response of the carotid artery of guinea pig fetuses through a methodology that encompasses experiments, modeling and numerical simulation. To this end, the isometric contraction test is carried out in ring samples subjected to different levels of KCl concentrations and pre-stretching. Then, a coupled mechanochemical model, aimed at describing the smooth cell behavior and its influence on the passive and active mechanical response of the vascular tissue, is calibrated from the experimental measurements. Due to the complex stress and strain fields developed in the artery, a finite element numerical simulation of the test is performed to fit the model parameters, where those related to the phosphorylation and dephosphorylation activity along with the load-bearing capacity of the myosin cross-bridges are found to be the most predominant when sensitizing the active response. The main strengths of the model are associated with the prediction of the stationary state of the active mechanical response of the tissue through a realistic description of the mechanochemical process carried out at its cellular level.

Analysis of the passive biomechanical behavior of a sheep-specific aortic artery in pulsatile flow conditions.

In this work, a novel numerical-experimental procedure is proposed, through the use of the Cardiac Simulation Test (CST), device that allows the exposure of the arterial tissue to in-vitro conditions, mimicking cardiac cycles generated by the heart. The main goal is to describe mechanical response of the arterial wall under physiological conditions, when it is subjected to a variable pressure wave over time, which causes a stress state affecting the biomechanical behavior of the artery wall. In order to get information related to stress and strain states, numerical simulation via finite element method, is performed under a condition of systolic and diastolic pressure. The description of this methodological procedure is performed with a sample corresponding to a sheep aorta without cardiovascular pathologies. There are two major findings: the evaluation of the mechanical properties of the sheep aorta through the above-mentioned tests and, the numerical simulation of the mechanical response under the conditions present in the CST. The results state that differences between numerical and experimental circumferential stretch in diastole and systole to distinct zones studied do not exceed 1%. However, greater discrepancies can be seen in the distensibility and incremental modulus, two main indicators, which are in the order of 30%. In addition, numerical results determine an increase of the principal maximum stress and strain between the case of systolic and diastolic pressure, corresponding to 31.1% and 14.9% for the stress and strain measurement respectively; where maximum values of these variables are located in the zone of the ascending aorta and the aortic arch.

Mechanical and Chemical Characterisation of TiN and AlTiSiN Coatings on a LPBF Processed IN718 Substrate.

Wear-resistant coatings development is progressively increasing steeply due to their advantages when applied to mechanical components subjected to abrasive and destructive environments. Titanium nitride (TiN) coating is typically used to enlarge tools and components' service life and improve their surface quality. On the other hand, AlTiSiN coating intends to be applied to more aggressive environments such as spatial satellites components exposed to solar radiation, extremely high temperatures, and random particles impact. In this work, specimens of Inconel 718 (IN718) were fabricated via laser powder bed fusion (LPBF), and physical vapour deposition (PVD)-deposited with TiN and AlTiSiN as coatings to mechanically and chemically characterise their surface. In this respect, microhardness testing and chemical analysis via glow discharge optical emission spectroscopy (GDOES) were performed. Later, roughness and wear behaviour analyses were carried out to evaluate the mechanical performance of both coatings and their surface and morphological features. The experimental observations allowed the analysis of both studied coatings by comparing them with the substrate processed via LPBF.

Biomechanical characterization of the passive response of the thoracic aorta in chronic hypoxic newborn lambs using an evolutionary strategy.

The present study involves experiments and modelling aimed at characterizing the passive structural mechanical behavior of the chronic hypoxic lamb thoracic aorta, whose gestation, birth and postnatal period were carried at high altitude (3600 masl). To this end, the mechanical response was studied via tensile and pressurization tests. The tensile and pressurization tests measurements were used simultaneously to calibrate the material parameters of the Gasser-Holzapfel-Ogden (GHO) hyperelasctic anisotropic constitutive model through an analytical-numerical optimization procedure solved with an evolutionary strategy that guarantees a stable response of the model. The model and procedure of calibration adequately adjust to the material behavior in a wide deformation range with an appropriate physical description. The results of this study predict the mechanical response of the lamb thoracic aorta under generalized loading states like those that can occur in physiological conditions and/or in systemic arterial hypertension. Finally, the novel use of the evolutionary strategy, together with the set of experiments and tools used in this study, provide a robust alternative to validate biomechanical characterizations.

Biomechanical Characterization of Scallop Shells Exposed to Ocean Acidification and Warming.

Increased carbon dioxide levels (CO2) in the atmosphere triggered a cascade of physical and chemical changes in the ocean surface. Marine organisms producing carbonate shells are regarded as vulnerable to these physical (warming), and chemical (acidification) changes occurring in the oceans. In the last decade, the aquaculture production of the bivalve scallop Argopecten purpuratus (AP) showed declined trends along the Chilean coast. These negative trends have been ascribed to ecophysiological and biomineralization constraints in shell carbonate production. This work experimentally characterizes the biomechanical response of AP scallop shells subjected to climate change scenarios (acidification and warming) via quasi-static tensile and bending tests. The experimental results indicate the adaptation of mechanical properties to hostile growth scenarios in terms of temperature and water acidification. In addition, the mechanical response of the AP subjected to control climate conditions was analyzed with finite element simulations including an anisotropic elastic constitutive model for a two-fold purpose: Firstly, to calibrate the material model parameters using the tensile test curves in two mutually perpendicular directions (representative of the mechanical behavior of the material). Secondly, to validate this characterization procedure in predicting the material's behavior in two mechanical tests.

Mechanical Characterization of the Elastoplastic Response of a C11000-H2 Copper Sheet.

This work presents an elastoplastic characterization of a rolled C11000-H2 99.90% pure copper sheet considering the orthotropic non-associated Hill-48 criterion together with a modified Voce hardening law. One of the main features of this material is the necking formation at small strains levels causing the early development of non-homogeneous stress and strain patterns in the tested samples. Due to this fact, a robust inverse calibration approach, based on an experimental-analytical-numerical iterative predictor-corrector methodology, is proposed to obtain the constitutive material parameters. This fitting procedure, which uses tensile test measurements where the strains are obtained via digital image correlation (DIC), consists of three steps aimed at, respectively, determining (a) the parameters of the hardening model, (b) a first prediction of the Hill-48 parameters based on the Lankford coefficients and, (c) corrected parameters of the yield and flow potential functions that minimize the experimental-numerical error of the material response. Finally, this study shows that the mechanical characterization carried out in this context is capable of adequately predicting the behavior of the material in the bulge test.

Analysis of the Part Distortions for Inconel 718 SLM: A Case Study on the NIST Test Artifact.

The present paper evaluates the misalignment and geometry distortion of the standard National Institute of Standards and Technology (NIST) test artifact in Inconel 718 alloy, when several layers with and without supports are employed to manufacture it by the Selective Laser Melting (SLM) process. To this end, a coordinate-measuring machine (CMM) is used to measure the geometrical distortion in each manufacturing configuration, following the same measurement protocol. The results show that the laser path strategy favors a thermal gradient which, consequently, induces geometrical distortions in the part. To prove this hypothesis, a numerical simulation is performed to determine the thermal gradient and the pattern of the residual stresses. It was found that the geometrical distortion certainly depends on the position of the feature position and laser strategy, where thermal cycles and residual thermal stresses had an impact in the end-part geometry, especially if a high strength-to-weight ratio commonly used in aeronautics is present.

Effects of melatonin on the passive mechanical response of arteries in chronic hypoxic newborn lambs.

Chronic hypoxia is a condition that increases the cardiovascular complications of newborns gestated and born at high altitude (HA), over 2500 m above sea level (masl). A particularly complex pathology is pulmonary arterial hypertension of the neonate (PHN), which is increased at HA due to hypobaric hypoxia. Basic and clinical research have recognized that new treatments are needed, because current ones are, in general, palliative and with low effectiveness. Therefore, recently we have proposed melatonin as a potential adjuvant treatment to improve cardiopulmonary function. However, melatonin effects on the mechanical response of the arteries and their microstructure are not known. This study assesses the effects of a neonatal treatment with daily low doses of melatonin on the passive biomechanical behavior of the aorta artery and main pulmonary artery of PHN lambs born in chronic hypobaric hypoxia (at 3600 masl). With this purpose, ex-vivo measurements were made on axial stretch, tensile and opening ring tests together with a histological analysis to explore the morphometry and microstructure of the arteries. Our results show that the passive mechanical properties of the aorta artery and main pulmonary artery of lambs do not seem to be affected by a treatment based on low melatonin doses. However, we found evidence that melatonin has microstructural effects, particularly, diminishing cell proliferation, which is an indicator of antiremodeling capacity. Therefore, the use of melatonin as an adjuvant against pathologies like PHN would present antiproliferative effect at the microstructural level, keeping the macroscopic properties of the aorta artery and main pulmonary artery.

Analysis of the Elastoplastic Response in the Torsion Test Applied to a Cylindrical Sample.

This work presents an experimental and numerical analysis of the mechanical behavior of a fixed-end SAE 1045 steel cylindrical specimen during the torsion test. To this end, an iterative numerical-experimental methodology is firstly proposed to assess the material response in the tensile test using a large strain elastoplasticity-based model solved in the context of the finite element method. Then, a 3D numerical simulation of the deformation process of the torsion test is tackled with this previously characterized model that proves to be able to predict the development of a high and localized triaxial stress and strain fields caused by the presence of high levels of angular deformation. Finally, the obtained numerical results are analytically studied with the cylindrical components of the Green-Lagrange strain tensor and experimentally validated with the measurements of shear strains via Digital Image Correlation (DIC) and the corresponding torque - twist angle curve.

Characterization of the Elastoplastic Response of Low Zn-Cu-Ti Alloy Sheets Using the CPB-06 Criterion.

Unlike other HCP metals such as titanium and magnesium, the behavior of zinc alloys has only been modeled in the literature. For the low Zn-Cu-Ti alloy sheet studied in this work, the anisotropy is clearly seen on the stress-strain curves and Lankford coefficients. These features impose a rigorous characterization and an adequate selection of the constitutive model to obtain an accurate representation of the material behavior in metal forming simulations. To describe the elastoplastic behavior of the alloy, this paper focuses on the material characterization through the application of the advanced Cazacu-Plunket-Barlat 2006 (CPB-06 for short) yield function combined with the well-known Hollomon hardening law. To this end, a two-stage methodology is proposed. Firstly, the material characterization is performed via tensile test measurements on sheet samples cut along the rolling, diagonal and transverse directions in order to fit the parameters involved in the associate CPB-06/Hollomon constitutive model. Secondly, these material parameters are assessed and validated in the simulation of the bulge test using different dies. The results obtained with the CPB-06/Hollomon model show a good agreement with the experimental data reported in the literature. Therefore, it is concluded that this model represents a consistent approach to estimate the behavior of Zn-Cu-Ti sheets under different forming conditions.

Numerical Simulation and Experimental Validation of Sheet Laser Forming Processes Using General Scanning Paths.

This work presents numerical simulations and an experimental validation of sheet laser forming processes using general scanning paths with different laser beam operating parameters (i.e., power, diameter, and scanning speed) in two specific graphite coated stainless steel blanks (i.e., with thicknesses of 0.3 mm and 0.6 mm for the AISI 302 and 304 alloys, respectively). To this end, three specific laser forming tests involving single S-shaped, multiple circular, and single piecewise linear scanning paths are carried out. On the other hand, the numerical simulation of these tests is performed via a coupled thermomechanical finite element formulation, accounting for large viscoplastic strains, temperature-dependent material properties, and convection-radiation phenomena. The final bending angles provided by this model are found to be in good agreement with the experimental measurements for all of the cases studied. Therefore, this modeling framework can be established as a reliable approach to predict the material thermomechanical response during sheet laser forming using general scanning paths.

Mechanical characterization of arteries affected by fetal growth restriction in guinea pigs (Cavia porcellus).

Fetal growth restriction (FGR) is a perinatal condition associated with a low birth weight that results mainly from maternal and placental constrains. Newborns affected by this condition are more likely to develop in the long term cardiovascular diseases whose origins would be in an altered vascular structure and function defined during fetal development. Thus, this study presents the modeling and numerical simulation of systemic vessels from guinea pig fetuses affected by FGR. We aimed to characterize the biomechanical properties of the arterial wall of FGR-derived the aorta, carotid, and femoral arteries by performing ring tensile and ring opening tests and, based on these data, to simulate the biomechanical behavior of FGR vessels under physiological conditions. The material parameters were first obtained from the experimental data of the ring tensile test. Then, the residual stresses were determined from the ring opening test and taken as initial stresses in the simulation of the ring tensile test. These two coupled steps are iteratively considered in a nonlinear least-squares algorithm to obtain the final material parameters. Then, the stress distribution changes along the arterial wall under physiological pressure were quantified using the adjusted material parameters. Overall, the obtained results provide a realistic approximation of the residual stresses and the changes in the mechanical behavior under physiological conditions.

Modelling and numerical simulation of the in vivo mechanical response of the ascending aortic aneurysm in Marfan syndrome.

Marfan syndrome (MFS) is a genetic disorder that affects connective tissue, impairing cardiovascular structures and function, such as heart valves and aorta. Thus, patients with Marfan disease have a higher risk of developing circulatory problems associated with mitral and aortic valves prolapse, manifested as dilated aorta and aortic aneurysm. However, little is known about the biomechanical characteristics of these structures affected with MFS. This study presents the modelling and simulation of the mechanical response of human ascending aortic aneurysms in MFS under in vivo conditions with intraluminal pressures within normotensive and hypertensive ranges. We obtained ascending aortic segments from five adults with MFS subjected to a vascular prosthesis implantation replacing an aortic aneurysm. We characterised the arterial samples via ex vivo tensile test measurements that enable fitting the material parameters of a hyperelastic isotropic constitutive model. Then, these material parameters were used in a numerical simulation of an ascending aortic aneurysm subjected to in vivo normotensive and hypertensive conditions. In addition, we assessed different constraints related to the movement of the aortic root. Overall, our results provide not only a realistic description of the mechanical behaviour of the vessel, but also useful data about stress/stretch-based criteria to predict vascular rupture. This knowledge may be included in the clinical assessment to determine risk and indicate surgical intervention.

Fetal Growth Restriction Induces Heterogeneous Effects on Vascular Biomechanical and Functional Properties in Guinea Pigs (Cavia porcellus).

Aim: Fetal growth restriction (FGR) is associated with a variety of cardiometabolic diseases in adulthood which could involve remodeling processes of the vascular walls that could start in the fetal period. However, there is no consensus whether this remodeling affects in a similar way the whole vascular system. We aimed to determine the effects of FGR on the vasoactive and biomechanical properties of umbilical and systemic vessels in fetal guinea pigs. Methods: FGR was induced by implanting ameroid occluders at mid-gestation in uterine arteries of pregnant guinea pigs, whilst the control group was exposed to simulated surgery. At the term of gestation, systemic arteries (aorta, carotid and femoral) and umbilical vessels were isolated to determine ex vivo contractile and biomechanical responses (stretch-stress until rupture) on a wire myograph, as well as opening angle and residual stresses. Histological characteristics in tissue samples were measured by van Gieson staining. Results: Aorta and femoral arteries from FGR showed an increased in biomechanical markers of stiffness (p < 0.01), contractile capacity (p < 0.05) and relative media thickness (p < 0.01), but a reduced internal diameter (p < 0.001), compared with controls. There were no differences in the biomechanical properties of carotid and umbilical from control and FGR fetuses, but FGR umbilical arteries had a decreased contractile response to KCl (p < 0.05) along with a reduced relative media thickness (p < 0.05). Conclusion: Altogether, these changes in functional, mechanical and morphological properties suggest that FGR is associated with a heterogeneous pro-constrictive vascular remodeling affecting mainly the lower body fetal arteries. These effects would be set during a pathologic pregnancy in order to sustain the fetal blood redistribution in the FGR and may persist up to adulthood increasing the risk of a cardiovascular disease.

Mechanical analysis of the ring opening test applied to human ascending aortas.

This work presents experiments, modelling and numerical simulation aimed at describing the mechanical response of human ascending aortas in the ring opening test. The objective is to quantify, from the opening angles measured in the test, the residual stress distribution along the artery wall and, afterwards, how this stress pattern changes when the artery is subjected to standard physiological pressures. The cases studied correspond to four groups including both healthy and pathological arteries. The tissues are characterized via tensile test measurements that enable to derive the material parameters of two constitutive models adopted in the present analysis. Overall, the numerical results obtained for all groups were found to be a useful data that allow to estimate the residual stress and their influence on the vessels under normal and hypertension physiological conditions.