Smeared Concept as a General Methodology in Finite Element Modeling of Physical Fields and Mechanical Problems in Composite Media

Kojić, Miloš

doi:10.24874/jsscm.2018.12.02.01

Cited by 15 publications

(5 citation statements)

References 9 publications

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“…Fundamental equations for CSFE. Composite smeared finite element (CSFE) for modeling diffusion within a fiber network and the surrounding used here is in analogy with representation of mass transport within a capillary system and surrounding tissue [37][38][39][40][41] . Since axial diffusion within fibers can be neglected, we here only present formulation of the radial diffusion in the smeared concept.…”

Section: Diffusion Within Fibersmentioning

confidence: 99%

Preparation and modeling of three‐layered PCL/PLGA/PCL fibrous scaffolds for prolonged drug release

Milošević

Stojanović

Simić

et al. 2020

Sci Rep

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The authors present the preparation procedure and a computational model of a three-layered fibrous scaffold for prolonged drug release. The scaffold, produced by emulsion/sequential electrospinning, consists of a poly(d,l-lactic-co-glycolic acid) (PLGA) fiber layer sandwiched between two poly(εcaprolactone) (PCL) layers. Experimental results of drug release rates from the scaffold are compared with the results of the recently introduced computational finite element (FE) models for diffusive drug release from nanofibers to the three-dimensional (3D) surrounding medium. Two different FE models are used: (1) a 3D discretized continuum and fibers represented by a simple radial one-dimensional (1D) finite elements, and (2) a 3D continuum discretized by composite smeared finite elements (CSFEs) containing the fiber smeared and surrounding domains. Both models include the effects of polymer degradation and hydrophobicity (as partitioning) of the drug at the fiber/surrounding interface. The CSFE model includes a volumetric fraction of fibers and diameter distribution, and is additionally enhanced by using correction function to improve the accuracy of the model. The computational results are validated on Rhodamine B (fluorescent drug l) and other hydrophilic drugs. Agreement with experimental results proves that numerical models can serve as efficient tools for drug release to the surrounding porous medium or biological tissue. It is demonstrated that the introduced three-layered scaffold delays the drug release process and can be used for the time-controlled release of drugs in postoperative therapy. A promising approach in modern medicine for drug delivery over a long time period and with a desirable rate is the use of nano-scaffolds 1-3 , and specifically electrospun-made scaffolds composed of drug loaded nanofiber mats 4-8. Fibers are preferably prepared using a biodegradable polymer 7 , and their main function is targeted and cites specific drug delivery in human body 1-5 , without any burst release 7 , and with improved physicochemical properties 6. This kind of drug delivery systems have provided many mechanisms that improve the therapeutic efficacy of both new and already existing drugs 7 , and may be now used for various paramedical and medical applications such as wound healing and cancer therapy 1-5. The advantages of using biodegradable polymers for drug delivery are: no need for the second surgery to remove the scaffold once the drug is released 9 , their enhanced biocompatibility, degradability, bioactivity and resorbability 8,10-12. Among the most commonly used biodegradable synthetic polymers, poly(lactic-co-glycolide (PLGA) copolymer is well recognized for drug delivery processes 13. PLGA is known for good biocompatibility and ability to achieve complete drug release 14 , which is the result of its degradation and erosion properties 15,16. Many

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Section: Diffusion Within Fibersmentioning

confidence: 99%

Preparation and modeling of three‐layered PCL/PLGA/PCL fibrous scaffolds for prolonged drug release

Milošević

Stojanović

Simić

et al. 2020

Sci Rep

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“…Perfusion and diffusion were simulated by using our developed Composite Smeared Finite Element (CSFE) method [ 15 , 16 ], which employs the concept of smeared physical fields, like fluid flow, molecule transport by convection and diffusion through capillary system and tissue, or capillary density. Fluid flow within capillaries is governed by the Hagen–Poiseuille law, while in tissue it is modeled according to the Darcy pressure–velocity relationship.…”

Section: Methodsmentioning

confidence: 99%

Attenuated Microcirculation in Small Metastatic Tumors in Murine Liver

et al. 2021

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Metastatic cancer disease is the major cause of death in cancer patients. Because those small secondary tumors are clinically hardly detectable in their early stages, little is known about drug biodistribution and permeation into those metastatic tumors potentially contributing to insufficient clinical success against metastatic disease. Our recent studies indicated that breast cancer liver metastases may have compromised perfusion of intratumoral capillaries hindering the delivery of therapeutics for yet unknown reasons. To understand the microcirculation of small liver metastases, we have utilized computational simulations to study perfusion and oxygen concentration fields in and around the metastases smaller than 700 µm in size at the locations of portal vessels, central vein, and liver lobule acinus. Despite tumor vascularization, the results show that blood flow in those tumors can be substantially reduced indicating the presence of inadequate blood pressure gradients across tumors. A low blood pressure may contribute to the collapsed intratumoral capillary lumen limiting tumor perfusion that phenomenologically corroborates with our previously published in vivo studies. Tumors that are smaller than the liver lobule size and originating at different lobule locations may possess a different microcirculation environment and tumor perfusion. The acinus and portal vessel locations in the lobule were found to be the most beneficial to tumor growth based on tumor access to blood flow and intratumoral oxygen. These findings suggest that microcirculation states of small metastatic tumors can potentially contribute to physiological barriers preventing efficient delivery of therapeutic substances into small tumors.

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“…First, the 1D balance equations are necessary to be transformed into the corresponding continuum format. The derivations of the continuum transport tensor, for a general physical field, are given (Kojic, 2018) and can be expressed as…”

Section: Smeared Model For Field Problemsmentioning

confidence: 99%

“…Considering the complexity of computational modeling of physical fields, such as pressure distribution, concentration of various molecules, or field of electrical potential within a body, or even within an organ, it is desirable to have a computational methodology feasible for practical applications. In our previous research, we have introduced a smeared concept for mass transport in capillary system and tissue (Kojic et al, 2017a(Kojic et al, ,b, 2018(Kojic et al, , 2019Kojic, 2018;Milosevic et al, 2018a) and demonstrated its superiority with respect to traditional modeling methods.…”

Section: Introductionmentioning

confidence: 99%

“…In the next section, we first summarize the governing equations of the gradientdriven processes: fluid flow through porous media, convectivediffusive particulate transport (including ions) and electrostatics; and then introduce a finite element (FE) form for these governing equations. In Section Smeared Model for Field Problems, the smeared methodology in a general form is summarized (Kojic, 2018), followed by specific forms related the problems described in Section A Summary of the Fundamental Equations for Gradient-Driven Physical Processes and FE Formulation. In Section Coupling Electrophysiology and Muscle Mechanics, we give a short description of coupling the smeared model for electrical potential with muscle mechanics.…”

Section: Introductionmentioning

confidence: 99%

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

Kojić

Milošević

Simić

et al. 2019

Front. Bioeng. Biotechnol.

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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.

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Smeared Concept as a General Methodology in Finite Element Modeling of Physical Fields and Mechanical Problems in Composite Media

Cited by 15 publications

References 9 publications

Preparation and modeling of three‐layered PCL/PLGA/PCL fibrous scaffolds for prolonged drug release

Preparation and modeling of three‐layered PCL/PLGA/PCL fibrous scaffolds for prolonged drug release

Attenuated Microcirculation in Small Metastatic Tumors in Murine Liver

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

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