In silico model development and optimization of in vitro lung cell population growth.

Tissue engineering predominantly relies on trial and error in vitro and ex vivo experiments to develop protocols and bioreactors to generate functional tissues. As an alternative, in silico methods have the potential to significantly reduce the timelines and costs of experimental programs for tissue engineering. In this paper, we propose a methodology to formulate, select, calibrate, and test mathematical models to predict cell population growth as a function of the biochemical environment and to design optimal experimental protocols for model inference of in silico model parameters. We systematically combine methods from the experimental design, mathematical statistics, and optimization literature to develop unique and explainable mathematical models for cell population dynamics. The proposed methodology is applied to the development of this first published model for a population of the airway-relevant bronchio-alveolar epithelial (BEAS-2B) cell line as a function of the concentration of metabolic-related biochemical substrates. The resulting model is a system of ordinary differential equations that predict the temporal dynamics of BEAS-2B cell populations as a function of the initial seeded cell population and the glucose, oxygen, and lactate concentrations in the growth media, using seven parameters rigorously inferred from optimally designed in vitro experiments.

Bilayer and Trilayer C3N/Blue-Phosphorene Heterostructures as Potential Anode Materials for Potassium-Ion Batteries.

Two-dimensional (2D) van der Waals heterostructures outperform conventional anode materials for postlithium-ion batteries in terms of mechanical, thermal, and electrochemical properties. This study systemically investigates the performance of bilayer and trilayer C3N/blue phosphorene (C3N/BlueP) heterostructures as anode materials for potassium-ion batteries (KIBs) using first-principles density functional theory calculations. This study reveals that the adsorption and diffusion of K ions on bilayer and trilayer C3N/BlueP heterostructures are markedly superior to those of their monolayer counterparts. A bilayer heterostructure (C3N/BlueP) effectively reduces the bandgap of the BlueP monolayer (1.98 eV) to 0.02 eV, whereas trilayer heterostructures (bilayer-C3N/BlueP and C3N/bilayer-BlueP) exhibit metallic behavior with no bandgap. Additionally, the theoretical capacity of the bilayer and trilayer heterostructures ranges from 636.7 to 755.5 mA h g-1, considerably higher than the theoretical capacity of other prospective 2D heterostructures for KIBs investigated in the literature. This study also shows that the heterostructures exhibit K-ion diffusion barriers as low as 0.042 eV, ensuring the relatively fast diffusion of K ions.

Nonlinear dependence (on ionic strength, pH) of surface charge density and zeta potential in microchannel electrokinetic flow.

In this work, a numerical method is proposed to predict the electrokinetic phenomena and combined with an experimental study of the surface charge density (ρs) and zeta potential (ζ) behavior is investigated for borosilicate immersed in KCl and NaCl electrolytes, and for imogolite immersed in KCl, CaCl2, and MgCl2 electrolytes. Simulations and experiments of the electrokinetic flows with electrolyte solutions were performed to accurately determine the electric double layer (EDL), ζ, and ρs at various electrolyte concentrations and pH. The zeta potential was experimentally determined and numerically predicted by solving the coupled governing equations of mass, species, momentum, and electrical field iteratively. Our numerical prediction shows that ζ for borosilicate develops strong nonlinear behavior with the ion concentration following a power-law. Likewise, the ρs obeys a nonlinear behavior, decreasing as the concentration increases. Moreover, for imogolite, both ζ and the ρs behave nonlinearly with the pH. The EDL for borosilicate and imogolite becomes thinner as the electrolyte concentration and pH increase; this behavior is caused by increased ρs, resulting in the higher attraction of the free charges. The reported nonlinear behavior describes more accurately the interaction of the nanoparticle surface charge with the electrolytes and its effect on the electrolyte transport properties.

Prediction of bird-beak configuration in thoracic endovascular aortic repair preoperatively using patient-specific finite element simulations.

Objectives: Formation of bird-beak configuration in thoracic endovascular aortic repair (TEVAR) has been shown to be correlated with the risk of complications such as type Ia endoleaks, stent graft migration, and collapse. The aim of this study was to use patient-specific computational simulations of TEVAR to predict the formation of bird-beak configuration preoperatively. Methods: Patient-specific TEVAR computational simulations are developed using a retrospective cohort of patients treated for thoracic aortic aneurysm. The preoperative computed tomography images were segmented to develop three-dimensional geometry of the thoracic aorta. These geometries were used in finite element simulations of stent graft deployment during TEVAR. Simulated results were compared against the postoperative computed tomography images to assess the accuracy of simulations in predicting the proximal position of a deployed stent graft and presence of bird-beak. In cases with a bird-beak configuration, the length and angle of the bird-beak were measured and compared between the simulated and postoperative results. Results: Twelve TEVAR patient cases were simulated. Computational simulations were able to accurately predict whether the proximal stent graft was fully apposed, proximal bare stents were protruded, or bird-beak configuration was present. In three cases with bird-beak configuration, simulations predicted the length and angle of the bird-beak with less than 10% and 24% error, respectively. Other factors such as a small aortic arch angle, small oversizing value, and landing zones close to the arch apex may have played a role in formation of bird-beak in these patients. Conclusions: Computational simulations of TEVAR accurately predicted the proximal position of a deployed stent graft and the presence of bird-beak preoperatively. The computational models were able to predict the length and angle of bird-beak configurations with good accuracy. These simulations can provide insight into the surgical planning process with the goal of minimizing bird-beak occurrence.

A Comparison of Vessel Patch Materials in Tetralogy of Fallot Patients Using Virtual Surgery Techniques.

Tetralogy of Fallot (ToF) is characterized by stenosis causing partial obstruction of the right ventricular outflow tract, typically alleviated through the surgical application of a vessel patch made from a biocompatible material. In this study, we use computational simulations to compare the mechanical performance of four patch materials for various stenosis locations. Nine idealized pre-operative ToF geometries were created by imposing symmetrical stenoses on each of three anatomical sub-regions of the pulmonary arteries of three patients with previously repaired ToF. A virtual surgery methodology was implemented to replicate the steps of vessel de-pressurization, surgical patching, and subsequent vessel expansion after reperfusion. Significant differences in patch average stress (p < 0.001) were found between patch materials. Biological patch materials (porcine xenopericardium, human pericardium) exhibited higher patch stresses in comparison to synthetic patch materials (Dacron and PTFE). Observed differences were consistent across the various stenosis locations and were insensitive to patient anatomy.

A modeling framework for computational simulations of thoracic endovascular aortic repair.

Thoracic endovascular aortic repair (TEVAR) is a minimally invasive treatment for thoracic aortic conditions including aneurysms and is associated with a number of postoperative stent graft related complications. Computational simulations of TEVAR have the potential to predict surgical outcomes and complications preoperatively. When using simulations for stent graft design and prediction of complications in a population, it is difficult to generalize patient-specific TEVAR computational models due to patient variability. This study proposes a novel modeling framework for creating realistic population-based computational models of TEVAR focused on aneurysms that allow for developing various clinically relevant geometric configurations and scenarios that are not easily attainable with limited patient data. The framework includes a methodology for developing population-based thoracic aortic geometries and defining age-dependent aortic tissue material models, as well as detailed steps and boundary conditions for finite element modeling of stent graft deployment during TEVAR. The simulation framework is illustrated for predicting the formation of a bird-beak configuration, a wedge-shaped gap at the proximal end of the deployed stent graft in TEVAR that leads to incomplete seal. A baseline TEVAR simulation model was developed along with three simulations in which the value of aortic curvature, aortic arch angle, or aortic tissue properties varied from the baseline model. Analyzing the length and angle of the bird-beak configuration in each case shows that the bird-beak size is sensitive to different values of the aortic geometry highlighting the importance of using realistic parameter values.

Identification of geometric and mechanical factors predictive of bird-beak configuration in thoracic endovascular aortic repair using computational models of stent graft deployment.

Objective: Formation of a bird-beak configuration in thoracic endovascular aortic repair (TEVAR) has been shown to be influenced by various factors. However, the main cause of bird-beak formation remains poorly understood. The hypothesis has been that the geometric and mechanical properties of both the aorta and the stent graft contribute to the formation and extent of a bird-beak configuration. The goal of the present study was to use parameter-based computational simulations of TEVAR to predict for bird-beak formation and identify its most significant contributing factors. Methods: In the present study, we considered five parameters for the computational simulations of TEVAR, including aortic curvature, aortic arch angle, age as a surrogate for thoracic aortic tissue properties, TEVAR landing zone, and stent graft oversizing. Using an experimental design approach, computational models for 160 TEVAR scenarios were developed by varying the values of the simulation parameters within clinically relevant ranges. The bird-beak length and angle were used as metrics to evaluate the simulation results. Statistical analysis of the simulation data using a random forest model was conducted to identify significant parameters and interactions. Results: The mean ± standard deviation of the bird-beak length and angle across 160 simulations were 4.32 ± 4.87 mm and 9.16° ± 12.21°, respectively. The largest mean bird-beak length and angle were found in the most distal location in zone 0 (10.04 mm) and zone 2 (21.48°), respectively. An inverse correlation was found between the aortic arch angle and the bird-beak length and angle. In ∼75% of the scenarios, increased stent graft oversizing either fully resolved the presence of the bird-beak configuration or had reduced its size. In the remaining 25%, oversizing minimally changed the bird-beak length and enlarged the bird-beak angle, which mainly occurred in cases with a smaller aortic arch angle and landing zones near the arch apex. This was justified by the mechanism of stent graft bending in the arch angulation. The aortic curvature and tissue properties were shown to be statistically insignificant in relation to bird-beak formation. Conclusions: Significant parameters predictive of a bird-beak configuration in TEVAR were identified, and the trends in which each parameter influenced the bird-beak size were determined. The findings from the present study can inform the surgical planning and device selection process with the goal of minimizing bird-beak formation.

Cell Inertia: Predicting Cell Distributions in Lung Vasculature to Optimize Re-endothelialization.

We created a transient computational fluid dynamics model featuring a particle deposition probability function that incorporates inertia to quantify the transport and deposition of cells in mouse lung vasculature for the re-endothelialization of the acellular organ. Our novel inertial algorithm demonstrated a 73% reduction in cell seeding efficiency error compared to two established particle deposition algorithms when validated with experiments based on common clinical practices. We enhanced the uniformity of cell distributions in the lung vasculature by increasing the injection flow rate from 3.81 ml/min to 9.40 ml/min. As a result, the cell seeding efficiency increased in both the numerical and experimental results by 42 and 66%, respectively.

Ascending aortic aneurysm haemodynamics are associated with aortic wall biomechanical properties.

OBJECTIVES: The effect of aortic haemodynamics on arterial wall properties in ascending thoracic aortic aneurysms (ATAAs) is not well understood. We aim to delineate the relationship between shear forces along the aortic wall and loco-regional biomechanical properties associated with the risk of aortic dissection. METHODS: Five patients with ATAA underwent preoperative magnetic resonance angiogram and four-dimensional magnetic resonance imaging. From these scans, haemodynamic models were constructed to estimate maximum wall shear stress (WSS), maximum time-averaged WSS, average oscillating shear index and average relative residence time. Fourteen resected aortic samples from these patients underwent bi-axial tensile testing to determine energy loss (ΔUL) and elastic modulus (E10) in the longitudinal (ΔULlong, E10long) and circumferential (ΔULcirc, E10circ) directions and the anisotropic index (AI) for each parameter. Nine resected aortic samples underwent peel testing to determine the delamination strength (Sd). Haemodynamic indices were then correlated to the biomechanical properties. RESULTS: A positive correlation was found between maximum WSS and ΔULlong rs=0.75, P = 0.002 and AIΔUL (rs=0.68, P=0.01). Increasing maximum time-averaged WSS was found to be associated with increasing ΔULlong (rs=0.73, P = 0.003) and AIΔUL (rs=0.62, P=0.02). Average oscillating shear index positively correlated with Sd (rs=0.73,P=0.04). No significant relationship was found between any haemodynamic index and E10, or between relative residence time and any biomechanical property. CONCLUSIONS: Shear forces at the wall of ATAAs are associated with local degradation of arterial wall viscoelastic hysteresis (ΔUL) and delamination strength, a surrogate for aortic dissection. Haemodynamic indices may provide insights into aortic wall integrity, ultimately leading to novel metrics for assessing risks associated with ATAAs.