On the generality of the finite element modeling physical fields in biological systems by the multiscale smeared concept (Kojic transport model).

The biomechanical and biochemical processes in the biological systems of living organisms are extremely complex. Advances in understanding these processes are mainly achieved by laboratory and clinical investigations, but in recent decades they are supported by computational modeling. Besides enormous efforts and achievements in this modeling, there still is a need for new methods that can be used in everyday research and medical practice.

A novel composite smeared finite element for mechanics (CSFEM): Some applications.

Background: Mechanical forces at the micro-scale level have been recognized as an important factor determining various biological functions. The study of cell or tissue mechanics is critical to understand problems in physiology and disease development.

Objective: The complexity of computational models and efforts made for their development in the past required significant robustness and different approaches in the modeling process.

Improved predictive performance of prostate biopsy collaborative group risk calculator when based on automated machine learning.

Background: The Prostate Biopsy Collaborative Group risk calculator (PBCG RC) has a moderate discriminatory capability. This study aimed to create automated machine learning (AutoML) PBCG RC for predicting the probability of any-grade and high-grade prostate cancer (PCa).

Methods: This retrospective, single-center study was carried out using the database with 832 patients who were subject to transrectal ultrasound-guided prostate biopsy with prostate-specific antigen (PSA) values from 2 to 50 ng/ml.

Attenuated Microcirculation in Small Metastatic Tumors in Murine Liver.

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.

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

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(ε-caprolactone) (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.

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

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.

Smeared multiscale finite element model for electrophysiology and ionic transport in biological tissue.

Basic functions of living organisms are governed by the nervous system through bidirectional signals transmitted from the brain to neural networks. These signals are similar to electrical waves. In electrophysiology the goal is to study the electrical properties of biological cells and tissues, and the transmission of signals.

Coupling tumor growth and bio distribution models.

We couple a tumor growth model embedded in a microenvironment, with a bio distribution model able to simulate a whole organ. The growth model yields the evolution of tumor cell population, of the differential pressure between cell populations, of porosity of ECM, of consumption of nutrients due to tumor growth, of angiogenesis, and related growth factors as function of the locally available nutrient. The bio distribution model on the other hand operates on a frozen geometry but yields a much refined distribution of nutrient and other molecules.

Correction function for accuracy improvement of the Composite Smeared Finite Element for diffusive transport in biological tissue systems.

Modeling of drug transport within capillaries and tissue remains a challenge, especially in tumors and cancers where the capillary network exhibits extremely irregular geometry. Recently introduced Composite Smeared Finite Element (CSFE) provides a new methodology of modeling complex convective and diffusive transport in the capillary-tissue system. The basic idea in the formulation of CSFE is in dividing the FE into capillary and tissue domain, coupled by 1D connectivity elements at each node.

A Computational Model for Drug Release from PLGA Implant.

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).

Progression-dependent transport heterogeneity of breast cancer liver metastases as a factor in therapeutic resistance.

Metastatic disease is a major cause of mortality in cancer patients. While many drug delivery strategies for anticancer therapeutics have been developed in preclinical studies of primary tumors, the drug delivery properties of metastatic tumors have not been sufficiently investigated. Therapeutic efficacy hinges on efficient drug permeation into the tumor microenvironment, which is known to be heterogeneous thus potentially making drug permeation heterogeneous, also.

Multiscale smeared finite element model for mass transport in biological tissue: From blood vessels to cells and cellular organelles.

One of the basic and vital processes in living organisms is mass exchange, which occurs on several levels: it goes from blood vessels to cells and organelles within cells. On that path, molecules, as oxygen, metabolic products, drugs, etc. Traverse different macro and micro environments - blood, extracellular/intracellular space, and interior of organelles; and also biological barriers such as walls of blood vessels and membranes of cells and organelles.

A composite smeared finite element for mass transport in capillary systems and biological tissue.

One of the key processes in living organisms is mass transport occurring from blood vessels to tissues for supplying tissues with oxygen, nutrients, drugs, immune cells, and - in the reverse direction - transport of waste products of cell metabolism to blood vessels. The mass exchange from blood vessels to tissue and vice versa occurs through blood vessel walls. This vital process has been investigated experimentally over centuries, and also in the last decades by the use of computational methods.

Extension of the composite smeared finite element (CSFE) to include lymphatic system in modeling mass transport in capillary systems and biological tissue.

We have recently introduced a composite smeared finite element (CSFE) to model gradient-driven mass transport in biological tissue. The transport from capillary system is smeared in a way to transform 1D transport to a continuum, while the tissue is considered as a continuum. Coupling between the smeared pressure and concentration field is achieved through 1D connectivity elements assigned at each FE node.

Mass release curves as the constitutive curves for modeling diffusive transport within biological tissue.

In diffusion governed by Fick's law, the diffusion coefficient represents the phenomenological material parameter and is, in general, a constant. In certain cases of diffusion through porous media, the diffusion coefficient can be variable (i.e.

A computational study of circulating large tumor cells traversing microvessels.

Circulating tumor cells (CTCs) are known to be a harbinger of cancer metastasis. The CTCs are known to circulate as individual cells or as a group of interconnected cells called CTC clusters. Since both single CTCs and CTC clusters have been detected in venous blood samples of cancer patients, they needed to traverse at least one capillary bed when crossing from arterial to venous circulation.

A multiscale MD-FE model of diffusion in composite media with internal surface interaction based on numerical homogenization procedure.

Mass transport by diffusion within composite materials may depend not only on internal microstructural geometry, but also on the chemical interactions between the transported substance and the material of the microstructure. Retrospectively, there is a gap in methods and theory to connect material microstructure properties with macroscale continuum diffusion characteristics. Here we present a new hierarchical multiscale model for diffusion within composite materials that couples material microstructural geometry and interactions between diffusing particles and the material matrix.