Sharif Digital Repository

Since physiological and pathological processes occur at nano-environments, nanotechnology has considered as an efficient tool for designing of next generation specific biomolecules with enhanced pharmacodynamic and pharmacodynamic properties. In the current investigation, by control of the size and hydrodynamic volume at the nanoscale, for the first time, physicochemical and pharmacokinetic properties of an anti-VEGFA nanobody was remarkably improved by attachment of a Proline-Alanine-Serine (PAS) rich sequence. The results elucidated unexpected impressive effects of PAS sequence on physicochemical properties especially on size, hydrodynamics radius, and even solubility of nanobody. CD... 

Flow-mediated dilation measurement in the brachial artery using ultrasound imaging (FMD-US) is a common noninvasive procedure for endothelial function evaluation in the peripheral arteries. As FMD-US is operator-dependent and involves onerous equipment, its use has been mostly confined to research settings. In this paper, we propose to use the more accessible finger photoplethysmogram signal in conjunction with the FMD test (FMD-PPG) as a surrogate method. To this end, a tube-load physiological model of the upper arterial path in the arm is developed. Signals acquired from young and elderly subjects (N=20) are then investigated using model parameter estimation by the genetic algorithm. Our... 

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... 

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... 

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.... 

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...