Sharif Digital Repository

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... 

Nitric Oxide (NO) provides myocardial oxygen demands of the heart during exercise and cardiac pacing and also prevents cardiovascular diseases such as atherosclerosis and platelet adhesion and aggregation. However, the direct in vivo measurement of NO in coronary arteries is still challenging. To address this matter, a mathematical model of dynamic changes of calcium and NO concentration in the coronary artery was developed for the first time. The model is able to simulate the effect of NO release in coronary arteries and its impact on the hemodynamics of the coronary arterial tree and also to investigate the vasodilation effects of arteries during cardiac pacing. For these purposes, flow... 

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... 

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... 

Endothelial cell migration is a crucial step in the process of new blood vessel formation - a necessary process to maintain cell viability inside thick tissue constructs. Here, we report a new method for maintaining cell viability and inducing cell migration using a perfused microfluidic platform based on collagen gel and a gradient hydrogel sheet. Due to the helpful role of the extracellular matrix components in cell viability, we developed a hydrogel sheet from decellularized tissue (DT) of the bovine heart and chitosan (CS). The results showed that hydrogel sheets with an optimum weight ratio of CS/DT = 2 possess a porosity of around 75%, a mechanical strength of 23 kPa, and display cell... 

The in vitro endothelial response of human umbilical vein endothelial cells was investigated on a poly (caprolactone)-based polyurethane surface vs an in situ TiO2-polyurethane nanocomposite surface, which has been produced as scaffolds for artificial vascular graft. The in situ synthesis of TiO2 nanoparticles in polyurethane provided surface properties that facilitated cellular adhesion, cell sensing, cell probing and especially cell migration. Cells on the nanocomposite surface have elongated morphology and were able to produce more extracellular matrix. All of these advantages led to an increase in the rate of endothelialization of the nanocomposite scaffold surface vs pure polyurethane.... 

Non-invasive measurement of flow-mediated dilation (FMD) in the brachial artery for assessing endothelial function is costly and operator-dependent, limiting its application to research cases. In this paper, an approach based on a physiological model between normalized central blood pressure and finger photoplethysmogram is presented. Baseline model parameters are estimated using a genetic algorithm in 30 subjects consisting of ten normal blood pressure (BP), ten high-BP and ten elderly volunteers. Beat-to-beat fitness values after reactive hyperaemia are calculated using baseline (before cuff occlusion) data. Results show that stimulus-induced changes are fairly described with a first order... 

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... 

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.... 

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... 

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... 

Hydrostatic pressure is one of the most fundamental and common mechanical stimuli in the body, playing a critical role in the homeostasis of all organ systems. Kidney function is affected by high blood pressure, namely hypertension, by the increased pressure acting on the glomerular capillary walls. This general effect of hypertension is diagnosed as a chronic disease, but underlying mechanistic causes are still not well understood. This paper reports a portable and adaptive device for studying the effects of hydrostatic pressure on a monolayer of cells. The fabricated device fits within a conventional incubation system and microscope. The effects of various pressures and durations were... 

Small diameter vascular grafts (<6 mm) are highly demanded for patients suffering from severe occluded arteries to be used as a bypass or substituted conduit. Fabricating a graft with appropriate structural, mechanical and cell growth properties which has simultaneously anti-thrombogenic trait is a challenge nowadays. Here, we proposed a bilayer heparinized vascular graft that can mimic the structural and mechanical characteristics close to those of the native coronary artery by combining electrospinning and freeze drying methods. In this study, the inner layer was made by co-electrospinning of synthetic polymer, poly-caprolactone (PCL) and the natural polymer, gelatin (Gel). Also, heparin... 

Small diameter vascular grafts (<6 mm) are highly demanded for patients suffering from severe occluded arteries to be used as a bypass or substituted conduit. Fabricating a graft with appropriate structural, mechanical and cell growth properties which has simultaneously anti-thrombogenic trait is a challenge nowadays. Here, we proposed a bilayer heparinized vascular graft that can mimic the structural and mechanical characteristics close to those of the native coronary artery by combining electrospinning and freeze drying methods. In this study, the inner layer was made by co-electrospinning of synthetic polymer, poly-caprolactone (PCL) and the natural polymer, gelatin (Gel). Also, heparin... 

A stereolithography-based bioprinting platform for multimaterial fabrication of heterogeneous hydrogel constructs is presented. Dynamic patterning by a digital micromirror device, synchronized by a moving stage and a microfluidic device containing four on/off pneumatic valves, is used to create 3D constructs. The novel microfluidic device is capable of fast switching between different (cell-loaded) hydrogel bioinks, to achieve layer-by-layer multimaterial bioprinting. Compared to conventional stereolithography-based bioprinters, the system provides the unique advantage of multimaterial fabrication capability at high spatial resolution. To demonstrate the multimaterial capacity of this... 

Hydrostatic pressure is one of the most fundamental and common mechanical stimuli in the body, playing a critical role in the homeostasis of all organ systems. Kidney function is affected by high blood pressure, namely hypertension, by the increased pressure acting on the glomerular capillary walls. This general effect of hypertension is diagnosed as a chronic disease, but underlying mechanistic causes are still not well understood. This paper reports a portable and adaptive device for studying the effects of hydrostatic pressure on a monolayer of cells. The fabricated device fits within a conventional incubation system and microscope. The effects of various pressures and durations were... 

Background: Understanding cancer development crossing several spatial-temporal scales is of great practical significance to better understand and treat cancers. It is difficult to tackle this challenge with pure biological means. Moreover, hybrid modeling techniques have been proposed that combine the advantages of the continuum and the discrete methods to model multiscale problems. Methods: In light of these problems, we have proposed a new hybrid vascular model to facilitate the multiscale modeling and simulation of cancer development with respect to the agent-based, cellular automata and machine learning methods. The purpose of this simulation is to create a dataset that can be used for... 

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... 

In this study, a new method for the simulation of the time-dependent behavior of actin cytoskeleton during cell shape change is proposed. For this purpose, a three-dimensional model of endothelial cell consisting of cell membrane, nucleus membrane, and main components of cytoskeleton, namely actin filaments, microtubules, and intermediate filaments is utilized. Actin binding proteins, which play a key role in regulating actin cytoskeleton behavior, are also simulated by using a novel technique. The actin cytoskeleton in this model is more dynamic and adoptable during cell deformation in comparison to previous models. The proposed model is subjected to compressive force between parallel micro... 

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...