The discrete multi-physics method applied to biomechanics

In this thesis, a fully Lagrangian approach called the Discrete Multi-Physics is adopted and applied to biomechanics. The Discrete Multi-Physics combines the Smoothed Particle Hydrodynamics, the Mass and Spring Model and the Discrete Element Method in a common particle-based framework. In the Discrete Multi-Physics, high deformations and contact of solid structures (e.g. valve’s leaflets during closing phase or colloid contact) can be easily modelled. In biological valve simulations, for instance, we were able to account for repeated opening-closing cycles and to introduce an agglomeration algorithm to model clotting. Besides cardiovascular and venous flows, we also applied the Discrete Multi-Physics to respiratory tracts for modelling (i) cilia motion and drug diffusion in the periciliary layer (ciliated epithelium) and (ii) the release of active ingredients in powder inhalers for drug delivery in the lungs

Two case studies of SPH modelling in biological system: large intestine and deep vein valves

Computational Fluid Dynamics (CFD) techniques has proven its adaptiveness and mutuality in various application for diversified fields. At the moment, the investigation of physical mechanics developed by CFD in physiological transportation has arisen great attention. This thesis aims at deepening the insight into the interactive mechanism between the periodic deformable human conduits and the conveyed fluid content. To start with a coupled method consists of Smoothed Particle Hydrodynamics (SPH) method and Coarse-Grained Molecular Dynamics (CGMD) I Mass-spring modelling (MSM) is adopted as it has proven its potentials in dealing with the transportation inside the deformable solid boundaries. The fluid part is simply simulated by the SPH method while the soft solid boundaries are mimicked by another one to yield the optimal utility of the coupled method. Our models developed for Gastric Intestine (GI) system are first validated by comparisons with PET experimental outcomes and are applied to the practical usage. Quantitative analysis is made among simulations to illustrate the mixing and transportation of food propelled by the muscle peristalsis. Then the method is further extended into the study of the venous system and the results indicate a good interpretation of the pathological study of the valve dysfunction and the venous development

Possible Assessment of Calf Venous Pump Efficiency by Computational Fluid Dynamics Approach

Three-dimensional simulations of peripheral, deep venous flow during muscular exercise in limbs of healthy subjects and in those with venous dysfunction were carried out by a computational fluid-dynamics (CFD) approach using the STAR CCM + platform. The aim was to assess the effects of valvular incompetence on the venous calf pump efficiency. The model idealizes the lower limb circulation by a single artery, a capillary bed represented by a porous region and a single vein. The focus is on a segment of the circuit which mimics a typical deep vein at the level of the calf muscle, such as the right posterior tibial vein. Valves are idealized as ball valves, and periodic muscle contractions are given by imposing time-dependent boundary conditions to the calf segment wall. Flow measurements were performed in two cross-sections downstream and upstream of the calf pump. Model results demonstrate a reduced venous return for incompetent valves during calf exercise. Two different degrees of valvular incompetence are considered, by restricting the motion of one or both valves. Model results showed that only the proximal valve is critical, with a 30% reduction of venous return during calf exercise in case of valvular incompetence: the net flow volume ejected by the calf in central direction was 0.14 mL per working cycle, against 0.2 mL for simulated healthy limbs. This finding appeared to be consistent with a 25% reduction of the calf ejection fraction, experimentally observed in chronic venous disease limbs compared with healthy limbs

Deep Multiphysics and Particle–Neuron Duality: A Computational Framework Coupling (Discrete) Multiphysics and Deep Learning

There are two common ways of coupling first-principles modelling and machine learning. In one case, data are transferred from the machine-learning algorithm to the first-principles model; in the other, from the first-principles model to the machine-learning algorithm. In both cases, the coupling is in series: the two components remain distinct, and data generated by one model are subsequently fed into the other. Several modelling problems, however, require in-parallel coupling, where the first-principle model and the machine-learning algorithm work together at the same time rather than one after the other. This study introduces deep multiphysics; a computational framework that couples first-principles modelling and machine learning in parallel rather than in series. Deep multiphysics works with particle-based first-principles modelling techniques. It is shown that the mathematical algorithms behind several particle methods and artificial neural networks are similar to the point that can be unified under the notion of particle–neuron duality. This study explains in detail the particle–neuron duality and how deep multiphysics works both theoretically and in practice. A case study, the design of a microfluidic device for separating cell populations with different levels of stiffness, is discussed to achieve this aim

Fluid-structure interaction of blood flow around a vein valve

Introduction: Venous valves are a type of one-way valves which conduct blood flow toward the heart and prevent its backflow. Any malfunction of these organs may cause serious problems in the circulatory system. Numerical simulation can give us detailed information and point to point data such as velocity, wall shear stress, and von Mises stress from veins with small diameters, as obtaining such data is almost impossible using current medical devices. Having detailed information about fluid flow and valves' function can help the treatment of the related diseases. Methods: In the present work, the blood flow through a venous valve considering the flexibility of the vein wall and valve leaflets is investigated numerically. The governing equations of fluid flow and solid domain are discretized and solved by the Galerkin finite element method. Results: The obtained results showed that the blood velocity increases from inlet to the leaflets and then decreases passing behind the valve. A pair of vortices and the trapped region was observed just behind the valves. These regions have low shear stresses and are capable of sediment formation. Conclusion: The von Mises stress which is a criterion for the breakdown of solid materials was obtained. It was also observed that a maximum value occurred at the bottom of the leaflets

A Coarse Grained Model for Viscoelastic Solids in Discrete Multiphysics Simulations

Viscoelastic bonds intended for Discrete Multiphysics (DMP) models are developed to allow the study of viscoelastic particles with arbitrary shape and mechanical inhomogeneity that are relevant to the pharmaceutical sector and that have not been addressed by the Discrete Element Method (DEM). The model is applied to encapsulate particles with a soft outer shell due, for example, to the partial ingress of moisture. This was validated by the simulation of spherical homogeneous linear elastic and viscoelastic particles. The method is based on forming a particle from an assembly of beads connected by springs or springs and dashpots that allow the sub-surface stress fields to be computed, and hence an accurate description of the gross deformation. It is computationally more expensive than DEM, but could be used to define more effective interaction law

Modelling and simulation of the hydrodynamics and mixing profiles in the human proximal colon using Discrete Multiphysics

The proximal part of the colon offers opportunities to prolong the absorption window following oral administration of a drug. In this work, we used computer simulations to understand how the hydrodynamics in the proximal colon might affect the release from dosage forms designed to target the colon. For this purpose, we developed and compared three different models: a completely-filled colon, a partially-filled colon and a partially-filled colon with a gaseous phase present (gas-liquid model). The highest velocities of the liquid were found in the completely-filled model, which also shows the best mixing profile, defined by the distribution of tracking particles over time. No significant differences with regard to the mixing and velocity profiles were found between the partially-filled model and the gas-liquid model. The fastest transit time of an undissolved tablet was found in the completely-filled model. The velocities of the liquid in the gas-liquid model are slightly higher along the colon than in the partially-filled model. The filling level has an impact on the exsisting shear forces and shear rates, which are decisive factors in the development of new drugs and formulations

Development of a digital twin of a tablet that mimics a real solid dosage form : differences in the dissolution profile in conventional mini-USP II and a biorelevant colon model

The performance of colon-targeted solid dosage forms is commonly assessed using standardised pharmacopeial dissolution apparatuses like the USP II or the miniaturised replica, the mini-USP II. However, these fail to replicate the hydrodynamics and shear stresses in the colonic environment, which is crucial for the tablet's drug release process. In this work, computer simulations are used to create a digital twin of a dissolution apparatus and to develop a method to create a digital twin of a tablet that behaves realistically. These models are used to investigate the drug release profiles and shear rates acting on a tablet at different paddle speeds in the mini-USP II and biorelevant colon models to understand how the mini-USP II can be operated to achieve more realistic (i.e., in vivo) hydrodynamic conditions. The behaviour of the tablet and the motility patterns used in the simulations are derived from experimental and in vivo data, respectively, to obtain profound insights into the tablet's disintegration/drug release processes. We recommend an "on-off" operating mode in the mini-USP II to generate shear rate peaks, which would better reflect the in vivo conditions of the human colon instead of constant paddle speed