in-silico-clinical-trials-for-cardiovascular-disease

<em>In Silico</em> Clinical Trials for Cardiovascular Disease

The SILICOFCM project mainly aims to develop a computational platform for in silico clinical trials of familial cardiomyopathies (FCMs). The unique ...

University of Kragujevac

Due to the relative ease of producing nanofibers with a core⁻shell structure, emulsion electrospinning has been investigated intensively in making nanofibrous drug delivery systems for controlled and sustained release. Predictions of drug release rates from the poly (d,l-lactic-co-glycolic acid) (PLGA) produced via emulsion electrospinning can be a very difficult task due to the complexity of the system. A computational finite element methodology was used to calculate the diffusion mass transport of Rhodamine B (fluorescent drug model). Degradation effects and hydrophobicity (partitioning phenomenon) at the fiber/surrounding interface were included in the models. The results are validated by experiments where electrospun PLGA nanofiber mats with different contents were used. A new approach to three-dimensional (3D) modeling of nanofibers is presented in this work. The authors have introduced two original models for diffusive drug release from nanofibers to the 3D surrounding medium discretized by continuum 3D finite elements: (1) A model with simple radial one-dimensional (1D) finite elements, and (2) a model consisting of composite smeared finite elements (CSFEs). Numerical solutions, compared to experiments, demonstrate that both computational models provide accurate predictions of the diffusion process and can therefore serve as efficient tools for describing transport inside a polymer fiber network and drug release to the surrounding porous medium.

A Computational Model for Drug Release from PLGA Implant.

Mass transport represents the most fundamental process in living organisms. It includes delivery of nutrients, oxygen, drugs, and other substances from the vascular system to tissue and transport of waste and other products from cells back to vascular and lymphatic network and organs. Furthermore, movement is achieved by mechanical forces generated by muscles in coordination with the nervous system. The signals coming from the brain, which have the character of electrical waves, produce activation within muscle cells. Therefore, from a physics perspective, there exist a number of physical fields within the body, such as velocities of transport, pressures, concentrations of substances, and electrical potential, which is directly coupled to biochemical processes of transforming the chemical into mechanical energy and further internal forces for motion. The overall problems of mass transport and electrophysiology coupled to mechanics can be investigated theoretically by developing appropriate computational models. Due to the enormous complexity of the biological system, it would be almost impossible to establish a detailed computational model for the physical fields related to mass transport, electrophysiology, and coupled fields. To make computational models feasible for applications, we here summarize a concept of smeared physical fields, with coupling among them, and muscle mechanics, which includes dependence on the electrical potential. Accuracy of the smeared computational models, also with coupling to muscle mechanics, is illustrated with simple example, while their applicability is demonstrated on a liver model with tumors present. The last example shows that the introduced methodology is applicable to large biological systems.

Smeared Multiscale Finite Element Models for Mass Transport and Electrophysiology Coupled to Muscle Mechanics.

Due to the relatively low fluid velocities in major arteries and veins, blood flow is by default laminar, however, turbulence can occur as a result of stenosis or other obstacles. Hemodynamic parameters like Wall Shear Stress or Oscillatory Shear Index can be used for plaque formation prediction, and these parameters are depended on the nature of the flow. Implementation of the k-ω turbulent flow in the Finite Element solver aims to improve numerical analysis of cardio-vascular condition development and progression. Calculation of turbulent fluid flow in this paper is performed using a two-equation turbulent finite element model that can calculate values in the viscous sublayer.

Article	Year
A Computational Model for Drug Release from PLGA Implant. Materials (Basel, Switzerland)\| PubMed ID: 30501079	2018
Smeared Multiscale Finite Element Models for Mass Transport and Electrophysiology Coupled to Muscle Mechanics. Frontiers in bioengineering and biotechnology\| PubMed ID: 31921800	2019
Turbulent finite element model applied for blood flow calculation in arterial bifurcation. Computer methods and programs in biomedicine\| PubMed ID: 34407452	2021

Vladimir Simic

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