Sharif Digital Repository

It is proved that the endothelial (artery inner lumen cells) function is associated with cardiovascular risk factors. Among all the common non-invasive methods employed in the research setting for assessing endothelial function, flow-mediated dilation is the most widely used one. This technique measures endothelial function by inducing reactive hyperemia using temporary arterial occlusion and measuring the resultant relative increase in blood vessel diameter via ultrasound. In this paper, the limitations associated with the ultrasound technique are overcome by using the photoplethysmogram (PPG) signal recorded during FMD. The correctness of this approach is investigated by modeling the AC... 

The main goal of this study is to investigate the role of vascular graft thickness in wall stress gradient in anastomosis region. Atherosclerosis is a common heart disease causes high mortality rates every year. The gold standard treatment of atherosclerosis is replacing with autologous vein extracted from patient's body. Since proper autologous vein is limited, researchers have made efforts to achieve compliance engineered blood vessels. Mechanical stress has great effect on both smooth muscle cells and endothelial cells and it is considered as a stimulus in plaque formation. In this study, we evaluate the role of thickness in wall stress of anastomosis region. For this purpose, two... 

In the recent years a great attention of research deals with different physical and biological aspects of the BBB structure, a robust shield that separates the blood and brain, a recent research held by the authors of this paper has focused on figuring out computing the diffusion coefficient of endothelial cell membrane. In this study, the major efforts have been concentrated on calculating a standardized measure for the amount of permeability and diffusion of this barrier. As a result, this work is dedicated to molecular dynamics (MD) simulation of calculating the interaction force between nano-particle and BBB membrane. data is recorded by using steered molecular dynamics simulation and... 

The function and morphology of Endothelial Cells (ECs) play a key role in atherosclerosis. The mechanical stimuli of ECs, such as Wall Shear Stress (WSS) and arterial wall strain, greatly inuence the function and morphology of these cells. The present article deals with computations of these stimuli for a 3D model of a healthy coronary artery bifurcation. The focus of the study is to propose an accurate method for computations of WSS and strains. Two approaches are considered: Coupled simultaneous simulation of arterial wall and blood flow, called fluid-Structure Interaction (FSI) simulation, and decoupled, which simulates each domain (fluid and solid domain) separately. The study... 

A cell migration numerical simulation is presented to mimic the motility of endothelial cells subjected to the concentration gradients of a Forebrain embryoniccortical neuron Conditioned Medium (CM). This factor was previously shflown to induce the directional chemotaxis of endothelial cells with an over-expressed G protein coupled receptor 124 (GPR 124). A cell simulator program incorporates basic elements of the cell cytoskeleton, including membrane, nucleus and cytoskeleton. The developed 2D cell model is capable of responding to concentration gradients of biochemical factors by changing the cytoskeleton arrangement. Random walk force, cell drag force and cell inertial effects are also... 

Various physical and biological aspects of the Blood Brain Barrier (BBB) structure still remain unfolded. Therefore, among the several mechanisms of drug delivery, only a few have succeeded in breaching this barrier, one of which is the use of Magnetic Nanoparticles (MNPs). However, a quantitative characterization of the BBB permeability is desirable to find an optimal magnetic force-field. In the present study, a molecular model of the BBB is introduced that precisely represents the interactions between MNPs and the membranes of Endothelial Cells (ECs) that form the BBB. Steered Molecular Dynamics (SMD) simulations of the BBB crossing phenomenon have been carried out. Mathematical modeling... 

Superparamagnetic iron oxide nanoparticles (SPIONs) functionalized with antimicrobial agents are promising infection-targeted therapeutic platforms when coupled with external magnetic stimuli. These antimicrobial nanoparticles (NPs) may offer advantages in fighting intracellular pathogens as well as biomaterial-associated infections. This requires the development of NPs with high antimicrobial activity without interfering with the biology of mammalian cells. Here, we report the preparation of biocompatible antimicrobial SPION@gold core-shell NPs based on covalent immobilization of the antimicrobial peptide (AMP) cecropin melittin (CM) (the conjugate is named AMP-NP). The minimal inhibitory... 

Nowadays, nanoparticles (NPs) are used in a variety of biomedical applications including brain disease diagnostics and subsequent treatments. Among the various types of NPs, magnetic nanoparticles (MNPs) have been implemented by many research groups for an array of life science applications. In this paper, we studied MNPs controlled delivery into the endothelial cells using a magnetic field. Dynamics equations of MNPs were defined in the continuous domain using control theory methods and were applied to crossing the cell membrane. This study, dedicated to clinical and biomedical research applications, offers a guideline for the generation of a magnetic field required for the delivery of... 

The main focus of this study is to address the possibility of using molecular dynamics (MD) simulation, as a computational framework, coupled with experimental assays, to optimize composite structures of a particular electrospun scaffold. To this aim, first, MD simulations were performed to obtain an initial theoretical insight into the capability of heterogeneous surfaces for protein adsorption. The surfaces were composed of six different blends of PVA (polyvinyl alcohol) and PCL (polycaprolactone) with completely unlike hydrophobicity. Next, MTT assay was performed on the electrospun scaffolds made from the same percentages of polymers as in MD models to gain an understanding of the... 

The delivery of growth factors is often challenging due to their short half-life, low stability, and rapid deactivation. In native tissues, the sulfated residual of glycosaminoglycan (GAG) polymer chains of proteoglycans immobilizes growth factors through the proteoglycans'/proteins' complexation with nanoscale organization. These biological assemblies can influence growth factor-cell surface receptor interactions, cell differentiation, cell-cell signaling, and mechanical properties of the tissues. Here, we introduce a facile procedure to prepare novel biomimetic proteoglycan nanocarriers, based on naturally derived polymers, for the immobilization and controlled release of growth factors.... 

Injectable hydrogels which mimic the physicochemical and electromechanical properties of cardiac tissue is advantageous for cardiac tissue engineering. Here, a newly-developed in situ forming double-network hydrogel derived from biological macromolecules (oxidized alginate (OA) and myocardial extracellular matrix (ECM)) with improved mechanical properties and electrical conductivity was optimized. 3-(2-aminoethyl amino) propyltrimethoxysilane (APTMS)-functionalized reduced graphene oxide (Amine-rGO) was added to this system with varied concentrations to promote electromechanical properties of the hydrogel. Alginate was partially oxidized with an oxidation degree of 5% and the resulting OA... 

Atherosclerosis is a world-spread and well-known disease. This disease strongly relates to the endothelial cells (ECs) function. Normally, the endothelial cells align in the flow direction in the atheroprotected sites; however, in the case of atheroprone sites these cells orient randomly. The mechanical stimuli such as wall shear stress and strains could determine the morphology and function of the endothelial cells. In the present study, we numerically simulated the left main coronary artery (LCA) and its branches to left anterior descending (LAD) and left circumflex coronary (LCX) artery using fluid-structure interaction (FSI) modeling. The results were presented as longitudinal and... 

The shape and morphology of endothelial cells (ECs) lining the blood vessels are a good indicator for atheroprone and atheroprotected sites. ECs of blood vessels experience both wall shear stress (WSS) and cyclic stretch (CS). These mechanical stimuli influence the shape and morphology of ECs. A few models have been proposed for predicting the morphology of ECs under WSS or CS. In the present study, a mathematical cell population model is developed to simulate the morphology of ECs under combined WSS and CS conditions. The model considers the cytoskeletal filaments, cell–cell interactions, and cell–extracellular matrix interactions. In addition, the reorientation and polymerization of... 

The morphology of endothelial cells (ECs) may be an indication for determining atheroprone sites. Until now, there has been no clinical imaging technique to visualize the morphology of ECs in the arteries. The present study introduces a computational technique for determining the morphology of ECs. This technique is a multiscale simulation consisting of the artery scale and the cell scale. The artery scale is a fluid-structure interaction simulation. The input for the artery scale is the geometry of the coronary artery, that is, the dynamic curvature of the artery due to the cardiac motion, blood flow, blood pressure, heart rate, and the mechanical properties of the blood and the arterial... 

Nowadays, nanoparticles (NPs) are used in a variety of biomedical applications including brain disease diagnostics and subsequent treatments. Among the various types of NPs, magnetic nanoparticles (MNPs) have been implemented by many research groups for an array of life science applications. In this paper, we studied MNPs controlled delivery into the endothelial cells using a magnetic field. Dynamics equations of MNPs were defined in the continuous domain using control theory methods and were applied to crossing the cell membrane. This study, dedicated to clinical and biomedical research applications, offers a guideline for the generation of a magnetic field required for the delivery of... 

Understanding the foreign body response (FBR) and desiging strategies to modulate such a response represent a grand challenge for implant devices and biomaterials. Here, the development of a microfluidic platform is reported, i.e., the FBR-on-a-chip (FBROC) for modeling the cascade of events during immune cell response to implants. The platform models the native implant microenvironment where the implants are interfaced directly with surrounding tissues, as well as vasculature with circulating immune cells. The study demonstrates that the release of cytokines such as monocyte chemoattractant protein 1 (MCP-1) from the extracellular matrix (ECM)-like hydrogels in the bottom tissue chamber... 

Background: Human amniotic membrane grafting could be potentially useful in ocular surface complications due to tissue similarity and the presence of factors that reduce inflammation, vascu-larization, and scarring. However, considerations like donor-derived infectious risk and the requirement of an invasive surgery limit the clinical application of such treatments. Moreover, the quick depletion of bioactive factors after grafting reduces the efficacy of treatments. Therefore, in the current study, the possibility of nano delivery of the bioactive factors extracted from the human amniotic membrane to the ocular surface was investigated. Materials and Methods: Nanoparticles were prepared... 

Organ-on-a-chip technology tries to mimic the complexity of native tissues in vitro. Important progress has recently been made in using this technology to study the gut with and without microbiota. These in vitro models can serve as an alternative to animal models for studying physiology, pathology, and pharmacology. While these models have greater physiological relevance than two-dimensional (2D) cell systems in vitro, endocrine and immunological functions in gut-on-a-chip models are still poorly represented. Furthermore, the construction of complex models, in which different cell types and structures interact, remains a challenge. Generally, gut-on-a-chip models have the potential to... 

Irregular hemodynamics affects the progression of various vascular diseases, such atherosclerosis or aneurysms. Despite the extensive hemodynamics studies on animal models, the inter-species differences between humans and animals hamper the translation of such findings. Recent advances in vascular tissue engineering and the suitability ofin vitromodels for interim analysis have increased the use ofin vitrohuman vascular tissue models. Although the effect of flow on endothelial cell (EC) pathophysiology and EC-flow interactions have been vastly studied in two-dimensional systems, they cannot be used to understand the effect of other micro- and macro-environmental parameters associated with... 

Endothelial inflammation as a prominent precursor to atherosclerosis elicits a distinct pathological surface expression of particular vascular proteins. To exhibit a site-specific behaviour, micro- and nanoparticles, as carriers of therapeutics or imaging agents, can distinguish and use these proteins as targeted docking sites. Here, a computational patient-specific model capturing the exclusive luminal qualities has been developed to study the transport and adsorption of particles decorated with proper antibodies over an atherosclerotic plaque located in the LAD artery of the patient. Particles, in nano- and micron sizes, have been decorated with Sialyl Lewisx (sLex), P-selectin aptamer...