Molecular dynamics simulation of thermal transport across a solid/liquid interface created by a meniscus.

Understandings heat transfer across a solid/liquid interface is crucial for establishing novel thermal control pathways in a range of energy applications. One of the major problems raised in this context is the impact of the three-phase contact line between solid, liquid, and gas on heat flux perturbations at the nanoscale. The focus of this research is the thermal transport via nanosized meniscus restricted between two solid walls. The molecular dynamics approach was used to consider different wetting states of the meniscus by varying the interaction potential between atoms of the substrate and the liquid. The influence of the meniscus size on the energy exchange between two solid walls was also studied. It was discovered that possessing a three-phase contact line reduces the interfacial boundary resistance between solid and liquid. Furthermore, the finite element method was employed to connect atomistic simulations with continuum mechanics. We show that the wetting angle and interfacial boundary resistance are essential important parameters for multiscale analysis of thermal engineering issues with precise microscale parametrization.

Applicability of the absence of equilibrium in quantum system fully coupled to several fermionic and bosonic heat baths.

The time evolution of an occupation number is studied for a fermionic or bosonic oscillator linearly fully coupled to several fermionic and bosonic heat baths. The influence of the characteristics of thermal reservoirs of different statistics on the nonstationary population probability is analyzed at large times. Applications of the absence of equilibrium in such systems for creating a dynamic (nonstationary) memory storage are discussed.

Non-Markovian dynamics of quantum systems coupled with several mixed fermionic-bosonic heat baths.

For the fermionic or bosonic oscillator fully coupled to several heat baths with mixed statistics, the analytical expressions for the occupation numbers are derived within the non-Markovian quantum Langevin approach. Employing two or three heat baths and the Ohmic dissipation with Lorenzian cutoffs, the role of statistics of the system and heat baths in the dynamics of the system is studied.

Finite element modelling of the developing infant femur using paired CT and MRI scans.

Bone finite element (FE) studies based on infant post-mortem computed tomography (CT) examinations are being developed to provide quantitative information to assist the differentiation between accidental and inflicted injury, and unsuspected underlying disease. As the growing skeleton contains non-ossified cartilaginous regions at the epiphyses, which are not well characterised on CT examinations, it is difficult to evaluate the mechanical behaviour of the developing whole bone. This study made use of paired paediatric post mortem femoral CT and magnetic resonance imaging (MRI) examinations at two different stages of development (4 and 7 months) to provide anatomical and constitutive information for both hard and soft tissues. The work aimed to evaluate the effect of epiphyseal ossification on the propensity to shaft fractures in infants. The outcomes suggest that the failure load of the femoral diaphysis in the models incorporating the non-ossified epiphysis is within the range of bone-only FE models. There may however be an effect on the metaphysis. Confirmation of these findings is required in a larger cohort of children.

Cardiometabolic assessment of lamin A/C gene mutation carriers: a phenotype-genotype correlation.

AIMS: Mutations of the LMNA gene encoding lamin A/C induce heterogeneous phenotypes ranging from cardiopathies and myopathies to lipodystrophies. The aim of this study was to compare cardiometabolic complications in patients with heterozygous LMNA mutations at the 482nd codon, the 'hotspot' for partial lipodystrophy, with carriers of other, non-R482 LMNA mutations. METHODS AND RESULTS: This study included 29 patients with R482 LMNA mutations, 29 carriers of non-R482 LMNA mutation and 19 control subjects. Cardiac and metabolic phenotypes were compared between groups. A family history of either cardiac implantable electronic devices (CIEDs; P < 0.001) or sudden death (P < 0.01) was more frequent in non-R482 than R482 carriers. The non-R482 carriers also had more abnormalities on electrocardiography and received CIEDs more often than R482 carriers (P < 0.001). On cardiac ultrasound, non-R482 patients had greater frequencies of left atrial enlargement (P < 0.05) and lower left ventricular ejection fractions (P < 0.01) than R482 carriers. In contrast, R482 carriers had lower BMI (P < 0.05), leptin (P < 0.01) and fat mass (P < 0.001), but higher intra-/total abdominal fat-mass ratios (P < 0.001) and prevalences of diabetes (P < 0.01) and hypertriglyceridaemia (P < 0.05) than non-R482 carriers, with a trend towards more coronary artery disease. However, non-R482 carriers had higher intra-/total abdominal fat-mass ratios (P < 0.02) and prevalences of diabetes (P < 0.001) and hypertriglyceridaemia (P < 0.05) than the controls. CONCLUSION: Non-R482 carriers present more frequently with arrhythmias than R482 carriers, who twice as often have diabetes, suggesting that follow-up for laminopathies could be adjusted for genotype. Non-R482 mutations require ultra-specialized cardiac follow-up, and coronary artery disease should not be overlooked. Although overlapping phenotypes are found, LMNA mutations essentially lead to tissue-specific diseases, favouring genotype-specific pathophysiological mechanisms.

Heat transfer in rough nanofilms and nanowires using full band ab initio Monte Carlo simulation.

The Boltzmann transport equation is one of the most relevant frameworks to study the heat transport at the nanoscale, beyond the diffusive regime and up to the micrometer-scale. In the general case of 3D devices, the particle Monte Carlo approach of phonon transport is particularly powerful and convenient, and requires reasonable computational resources. In this work, we propose an original and versatile particle Monte Carlo approach parametrized by using ab initio data. Both the phonon dispersion and the phonon-phonon scattering rates have been computed by DFT calculation in the entire 3D Brillouin zone. To treat the phonon transport at rough interfaces, a combination of specular and diffuse reflections has been implemented in phase space. Thermal transport has been investigated in nanowires and thin films made of cubic and hexagonal Silicon, including edge roughness, in terms of effective thermal conductivity, phonon band contributions and heat flux orientation. It is shown that the effective thermal conductivity in quasi-ballistic regime obtained from our Monte Carlo simulation cannot be accurately fitted by simple semi-analytical Matthiessen-like models and that spectral approaches are mandatory to get good results. Our full band approach shows that some phonon branches exhibiting a negative group velocity in some parts of the Brillouin zone may contribute negatively to the total thermal flux. Besides, the thermal flux clearly appears to be oriented along directions of high density of states. The resulting anisotropy of the heat flux is discussed together with the influence of rough interfaces.

Comparison of HR-pQCT- and microCT-based finite element models for the estimation of the mechanical properties of the calcaneus trabecular bone.

The calcaneus bone is formed of extensive trabecular bone and is therefore well suited to be used as an example of loaded bone to establish the ability of combining microfinite element (microFE) technique with high-resolution peripheral quantitative computed tomography (HR-pQCT) in determining its mechanical properties. HR-pQCT is increasingly used as a tool for in vivo bone clinical research, but its use has been limited to the distal radius and tibia. The goal of this study was to determine the applicability of HR-pQCT-derived microFE models of the calcaneus trabecular bone with 82 µm voxel size with reference to higher-resolution microCT-based models taken as gold standard. By comparing the outputs of microFE models generated from both HR-pQCT and microCT images of the trabecular bone of five calcaneus cadaveric specimens, it was found that the HR-pQCT-based models predicted mechanical properties for fracture load, total reaction force and von Mises stress are considerably different from microCT-based counterparts by 33, 64 and 70%, respectively. Also, the morphological analysis showed a comprehensive geometrical difference between HR-pQCT-based microFE models and their microCT-based equivalents. The results of the HR-pQCT-based models were found to have strong dependency on the threshold value chosen to binarise the images prior to finite element modelling. In addition, it was found that the voxel size has a strong impact on accuracy of imaged-based microFE models compared to other factors such as the presence of soft tissue and image scanning integration time. Therefore, although HR-pQCT has shown to be useful to predict overall structural and biomechanical changes, it is limited in providing local accurate biomechanical properties of trabecular bone and therefore should be used with caution when assessing bone remodelling through local changes of trabecular bone apposition and resorption in disease treatment monitoring.

Non-Markovian dynamics of fermionic and bosonic systems coupled to several heat baths.

Employing the fermionic and bosonic Hamiltonians for the collective oscillator linearly FC-coupled with several heat baths, the analytical expressions for the collective occupation number are derived within the non-Markovian quantum Langevin approach. The master equations for the occupation number of collective subsystem are derived and discussed. In the case of Ohmic dissipation with Lorenzian cutoffs, the possibility of reduction of the system with several heat baths to the system with one heat bath is analytically demonstrated. For the fermionic and bosonic systems, a comparative analysis is performed between the collective subsystem coupled to two heat baths and the reference case of the subsystem coupled to one bath.

Micromechanical study of the load transfer in a polycaprolactone-collagen hybrid scaffold when subjected to unconfined and confined compression.

Scaffolds are used in diverse tissue engineering applications as hosts for cell proliferation and extracellular matrix formation. One of the most used tissue engineering materials is collagen, which is well known to be a natural biomaterial, also frequently used as cell substrate, given its natural abundance and intrinsic biocompatibility. This study aims to evaluate how the macroscopic biomechanical stimuli applied on a construct made of polycaprolactone scaffold embedded in a collagen substrate translate into microscopic stimuli at the cell level. Eight poro-hyperelastic finite element models of 3D printed hybrid scaffolds from the same batch were created, along with an equivalent model of the idealized geometry of that scaffold. When applying an 8% confined compression at the macroscopic level, local fluid flow of up to 20 [Formula: see text]m/s and octahedral strain levels mostly under 20% were calculated in the collagen substrate. Conversely unconfined compression induced fluid flow of up to 10 [Formula: see text]m/s and octahedral strain from 10 to 35%. No relevant differences were found amongst the scaffold-specific models. Following the mechanoregulation theory based on Prendergast et al. (J Biomech 30:539-548, 1997. https://doi.org/10.1016/S0021-9290(96)00140-6 ), those results suggest that mainly cartilage or fibrous tissue formation would be expected to occur under unconfined or confined compression, respectively. This in silico study helps to quantify the microscopic stimuli that are present within the collagen substrate and that will affect cell response under in vitro bioreactor mechanical stimulation or even after implantation.

Flow perfusion rate modulates cell deposition onto scaffold substrate during cell seeding.

The combination of perfusion bioreactors with porous scaffolds is beneficial for the transport of cells during cell seeding. Nonetheless, the fact that cells penetrate into the scaffold pores does not necessarily imply the interception of cells with scaffold substrate and cell attachment. An in vitro perfusion system was built to relate the selected flow rate with seeding efficiency. However, the in vitro model does not elucidate how the flow rate affects the transport and deposition of cells onto the scaffold. Thus, a computational model was developed mimicking in vitro conditions to identify the mechanisms that bring cells to the scaffold from suspension flow. Static and dynamic cell seeding configurations were investigated. In static seeding, cells sediment due to gravity until they encounter the first obstacle. In dynamic seeding, 12, 120 and 600 [Formula: see text] flow rates were explored under the presence or the absence of gravity. Gravity and secondary flow were found to be key factors for cell deposition. In vitro and in silico seeding efficiencies are in the same order of magnitude and follow the same trend with the effect of fluid flow; static seeding results in higher efficiency than dynamic perfusion although irregular spatial distribution of cells was found. In dynamic seeding, 120 [Formula: see text] provided the best seeding results. Nevertheless, the perfusion approach reports low efficiencies for the scaffold used in this study which leads to cell waste and low density of cells inside the scaffold. This study suggests gravity and secondary flow as the driving mechanisms for cell-scaffold deposition. In addition, the present in silico model can help to optimize hydrodynamic-based seeding strategies prior to experiments and enhance cell seeding efficiency.

µ-Particle tracking velocimetry and computational fluid dynamics study of cell seeding within a 3D porous scaffold.

Cell seeding of 3D scaffolds is a critical step in tissue engineering since the final tissue properties are related to the initial cell distribution and density within the scaffold unit. Perfusion systems can transport cells to the scaffold however; the fact that cells flow inside the scaffold pores does not guarantee cell deposition onto the scaffold substrate and cell attachment. The aim of this study was to investigate how fluid flow conditions modulate cell motion and deposition during perfusion. For such a purpose, a multiphase-based computational fluid dynamics (CFD) model was developed in conjunction with particle tracking velocimetry experiments (PTV) which for the first time were applied to observe cell seeding inside a 3D scaffold. CFD and PTV results showed the strong effect of gravity for lower flow rates leading to cell sedimentation and poor transport of cells to the scaffold. Higher flow rates help overcome the effect of gravity so more cells travelling inside the scaffold were found. Nonetheless, fluid flow drags cells along the fluid streamlines without intercepting the scaffold substrate. As a consequence, if cells do not deposit into the scaffold substrate, cell adhesion cannot occur. Therefore, cell-scaffold interception should be promoted and the present computational model which predicts the effect of gravity and fluid drag on cells trajectories could serve to optimise bioreactors and enhance cell seeding efficiency.

Short bursts of cyclic mechanical compression modulate tissue formation in a 3D hybrid scaffold.

Among the cues affecting cells behaviour, mechanical stimuli are known to have a key role in tissue formation and mineralization of bone cells. While soft scaffolds are better at mimicking the extracellular environment, they cannot withstand the high loads required to be efficient substitutes for bone in vivo. We propose a 3D hybrid scaffold combining the load-bearing capabilities of polycaprolactone (PCL) and the ECM-like chemistry of collagen gel to support the dynamic mechanical differentiation of human embryonic mesodermal progenitor cells (hES-MPs). In this study, hES-MPs were cultured in vitro and a BOSE Bioreactor was employed to induce cells differentiation by mechanical stimulation. From day 6, samples were compressed by applying a 5% strain ramp followed by peak-to-peak 1% strain sinewaves at 1Hz for 15min. Three different conditions were tested: unloaded (U), loaded from day 6 to day 10 (L1) and loaded as L1 and from day 16 to day 20 (L2). Cell viability, DNA content and osteocalcin expression were tested. Samples were further stained with 1% osmium tetroxide in order to investigate tissue growth and mineral deposition by micro-computed tomography (µCT). Tissue growth involved volumes either inside or outside samples at day 21 for L1, suggesting cyclic stimulation is a trigger for delayed proliferative response of cells. Cyclic load also had a role in the mineralization process preventing mineral deposition when applied at the early stage of culture. Conversely, cyclic load during the late stage of culture on pre-compressed samples induced mineral formation. This study shows that short bursts of compression applied at different stages of culture have contrasting effects on the ability of hES-MPs to induce tissue formation and mineral deposition. The results pave the way for a new approach using mechanical stimulation in the development of engineered in vitro tissue as replacement for large bone fractures.

2D µ-Particle Image Velocimetry and Computational Fluid Dynamics Study Within a 3D Porous Scaffold.

Transport properties of 3D scaffolds under fluid flow are critical for tissue development. Computational fluid dynamics (CFD) models can resolve 3D flows and nutrient concentrations in bioreactors at the scaffold-pore scale with high resolution. However, CFD models can be formulated based on assumptions and simplifications. µ-Particle image velocimetry (PIV) measurements should be performed to improve the reliability and predictive power of such models. Nevertheless, measuring fluid flow velocities within 3D scaffolds is challenging. The aim of this study was to develop a µPIV approach to allow the extraction of velocity fields from a 3D additive manufacturing scaffold using a conventional 2D µPIV system. The µ-computed tomography scaffold geometry was included in a CFD model where perfusion conditions were simulated. Good agreement was found between velocity profiles from measurements and computational results. Maximum velocities were found at the centre of the pore using both techniques with a difference of 12% which was expected according to the accuracy of the µPIV system. However, significant differences in terms of velocity magnitude were found near scaffold substrate due to scaffold brightness which affected the µPIV measurements. As a result, the limitations of the µPIV system only permits a partial validation of the CFD model. Nevertheless, the combination of both techniques allowed a detailed description of velocity maps within a 3D scaffold which is crucial to determine the optimal cell and nutrient transport properties.

Mechanical response of 3D Insert® PCL to compression.

3D polymeric scaffolds are increasingly used for in vitro experiments aiming to mimic the environment found in vivo, to support for cellular growth and to induce differentiation through the application of external mechanical cues. In research, experimental results must be shown to be reproducible to be claimed as valid and the first clause to ensure consistency is to provide identical initial experimental conditions between trials. As a matter of fact, 3D structures fabricated in batch are supposed to present a highly reproducible geometry and consequently, to give the same bulk response to mechanical forces. This study aims to measure the overall mechanical response to compression of commercially available 3D Insert PCL scaffolds (3D PCL) fabricated in series by fuse deposition and evaluate how small changes in the architecture of scaffolds affect the mechanical response. The apparent elastic modulus (Ea) was evaluated by performing quasi-static mechanical tests at various temperatures showing a decrease in material stiffness from 5MPa at 25°C to 2.2MPa at 37°C. Then, a variability analysis revealed variations in Ea related to the repositioning of the sample into the testing machine, but also consistent differences comparing different scaffolds. To clarify the source of the differences measured in the mechanical response, the same scaffolds previously undergoing compression, were scanned by micro computed tomography (µCT) to identify any architectural difference. Eventually, to clarify the contribution given by differences in the architecture to the standard deviation of Ea, their mechanical response was qualitatively compared to a compact reference material such as polydimethylsiloxane (PDMS). This study links the geometry, architecture and mechanical response to compression of 3D PCL scaffolds and shows the importance of controlling such parameters in the manufacturing process to obtain scaffolds that can be used in vitro or in vivo under reproducible conditions.

Combined numerical and experimental biomechanical characterization of soft collagen hydrogel substrate.

This work presents a combined experimental-numerical framework for the biomechanical characterization of highly hydrated collagen hydrogels, namely with 0.20, 0.30 and 0.40% (by weight) of collagen concentration. Collagen is the most abundant protein in the extracellular matrix of animals and humans. Its intrinsic biocompatibility makes collagen a promising substrate for embedding cells within a highly hydrated environment mimicking natural soft tissues. Cell behaviour is greatly influenced by the mechanical properties of the surrounding matrix, but the biomechanical characterization of collagen hydrogels has been challenging up to now, since they present non-linear poro-viscoelastic properties. Combining the stiffness outcomes from rheological experiments with relevant literature data on collagen permeability, poroelastic finite element (FE) models were developed. Comparison between experimental confined compression tests available in the literature and analogous FE stress relaxation curves showed a close agreement throughout the tests. This framework allowed establishing that the dynamic shear modulus of the collagen hydrogels is between 0.0097 ± 0.018 kPa for the 0.20% concentration and 0.0601 ± 0.044 kPa for the 0.40% concentration. The Poisson's ratio values for such conditions lie within the range of 0.495-0.485 for 0.20% and 0.480-0.470 for 0.40%, respectively, showing that rheology is sensitive enough to detect these small changes in collagen concentration and thus allowing to link rheology results with the confined compression tests. In conclusion, this integrated approach allows for accurate constitutive modelling of collagen hydrogels. This framework sets the grounds for the characterization of related hydrogels and to the use of this collagen parameterization in more complex multiscale models.

The inter-sample structural variability of regular tissue-engineered scaffolds significantly affects the micromechanical local cell environment.

Rapid prototyping techniques have been widely used in tissue engineering to fabricate scaffolds with controlled architecture. Despite the ability of these techniques to fabricate regular structures, the consistency with which these regular structures are produced throughout the scaffold and from one scaffold to another needs to be quantified. Small variations at the pore level can affect the local mechanical stimuli sensed by the cells thereby affecting the final tissue properties. Most studies assume rapid prototyping scaffolds as regular structures without quantifying the local mechanical stimuli at the cell level. In this study, a computational method using a micro-computed tomography-based scaffold geometry was developed to characterize the mechanical stimuli within a real scaffold at the pore level. Five samples from a commercial polycaprolactone scaffold were analysed and computational fluid dynamics analyses were created to compare local velocity and shear stress values at the same scaffold location. The five samples did not replicate the computer-aided design (CAD) scaffold and velocity and shear stress values were up to five times higher than the ones calculated in the CAD scaffold. In addition high variability among samples was found: at the same location velocity and shear stress values could be up to two times higher from sample to sample. This study shows that regular scaffolds need to be thoroughly analysed in order to quantify real cell mechanical stimuli so inspection methods should be included as part of the fabrication process.

The role of endplate poromechanical properties on the nutrient availability in the intervertebral disc.

OBJECTIVE: To investigate the relevance of the human vertebral endplate poromechanics on the fluid and metabolic transport from and to the intervertebral disc (IVD) based on educated estimations of the poromechanical parameter values of the bony endplate (BEP). METHODS: 50 micro-models of different BEP samples were generated from µCTs of lumbar vertebrae and allowed direct determination of porosity values. Permeability values were calculated by using the micro-models, through the simulation of permeation via computational fluid dynamics. These educated ranges of porosity and permeability values were used as inputs for mechano-transport simulations to assess their effect on both the distributions of metabolites within an IVD model and the poromechanical calculations within the cartilaginous part of the endplate i.e., the cartilage endplate (CEP). RESULTS: BEP effective permeability was highly correlated to local variations of porosity (R(2) ≈ 0.88). Universal patterns between bone volume fraction and permeability arose from these results and from other experimental data in the literature. These variations in BEP permeability and porosity had negligible effects on the distributions of metabolites within the disc. In the CEP, the variability of the poromechanical properties of the BEP did not affect the predicted consolidation but induced higher fluid velocities. CONCLUSIONS: The present paper provides the first sets of thoroughly identified BEP parameter values that can be further used in patient-specific poromechanical studies. Representing BEP structural changes through variations in poromechanical properties did not affect the diffusion of metabolites. However, attention might be paid to alterations in fluid velocities and cell mechano-sensing within the CEP.

Material property discontinuities in intervertebral disc porohyperelastic finite element models generate numerical instabilities due to volumetric strain variations.

Numerical studies of the intervertebral disc (IVD) are important to better understand the load transfer and the mechanobiological processes within the disc. Among the relevant calculations, fluid-related outputs are critical to describe and explore accurately the tissue properties. Porohyperelastic finite element models of IVD can describe accurately the disc behaviour at the organ level and allow the inclusion of fluid effects. However, results may be affected by numerical instabilities when fast load rates are applied. We hypothesized that such instabilities would appear preferentially at material discontinuities such as the annulus-nucleus boundary and should be considered when testing mesh convergence. A L4-L5 IVD model including the nucleus, annulus and cartilage endplates were tested under pure rotational loads, with different levels of mesh refinement. The effect of load relaxation and swelling were also studied. Simulations indicated that fluid velocity oscillations appeared due to numerical instability of the pore pressure spatial derivative at material discontinuities. Applying local refinement only was not enough to eliminate these oscillations. In fact, mesh refinements had to be local, material-dependent, and supplemented by the creation of a material transition zone, including interpolated material properties. Results also indicated that oscillations vanished along load relaxation, and faster attenuation occurred with the incorporation of the osmotic pressure. We concluded that material discontinuities are a major cause of instability for poromechanical calculations in multi-tissue models when load velocities are simulated. A strategy was presented to address these instabilities and recommendations on the use of IVD porohyperelastic models were given.