Sharif Digital Repository

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... 

There are limitations in current medications of articular cartilage injuries. Although injectable bioactive hydrogels are promising options, they have decreased biomechanical performance. Researchers should consider many factors when providing solutions to overcome these challenges. In this study, we created an injectable composite hydrogel from chitosan and human acellular cartilage extracellular matrix (ECM) particles. In order to enhance its mechanical properties, we reinforced this hydrogel with microporous microspheres composed of the same materials as the structural building blocks of the scaffold. Articular cartilage from human donors was decellularized by a combination of physical,... 

Generation of reactive oxygen species, delayed blood clotting, prolonged inflammation, bacterial infection, and slow cell proliferation are the main challenges of effective wound repair. Herein, a multifunctional extracellular matrix-mimicking hydrogel is fabricated through abundant hydrogen bonding among the functional groups of gelatin and tannic acid (TA) as a green chemistry approach. The hydrogel shows adjustable physicochemical properties by altering the concentration of TA and it represents high safety features both in vitro and in vivo on fibroblasts, red blood cells, and mice organs. In addition to the merit of facile encapsulation of cell proliferation-inducing hydrophilic drugs,... 

Generation of reactive oxygen species, delayed blood clotting, prolonged inflammation, bacterial infection, and slow cell proliferation are the main challenges of effective wound repair. Herein, a multifunctional extracellular matrix-mimicking hydrogel is fabricated through abundant hydrogen bonding among the functional groups of gelatin and tannic acid (TA) as a green chemistry approach. The hydrogel shows adjustable physicochemical properties by altering the concentration of TA and it represents high safety features both in vitro and in vivo on fibroblasts, red blood cells, and mice organs. In addition to the merit of facile encapsulation of cell proliferation-inducing hydrophilic drugs,... 

Background: Researchers are trying to study the mechanism of neural stem cells (NSCs) differentiation to oligodendrocyte-like cells (OLCs) as well as to enhance the selective differentiation of NSCs to oligodendrocytes. However, the limitation in nerve tissue acces-sibility to isolate the NSCs as well as their differentiation toward oligodendrocytes is still challenging. Purpose: In the present study, a hybrid polycaprolactone (PCL)-gelatin nanofiber scaffold mimicking the native extracellular matrix and axon morphology to direct the differentiation of bone marrow-derived NSCs to OLCs was introduced. Materials and Methods: In order to achieve a sustained release of T3, this factor was... 

This study presents a novel statistical volume element (SVE) for micromechanical modeling of the white matter structures, with histology-informed randomized distribution of axonal tracts within the extracellular matrix. The model was constructed based on the probability distribution functions obtained from the results of diffusion tensor imaging as well as the histological observations of scanning electron micrograph, at two structures of white matter susceptible to traumatic brain injury, i.e. corpus callosum and corona radiata. A simplistic representative volume element (RVE) with symmetrical arrangement of fully alligned axonal fibers was also created as a reference for comparison. A... 

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... 

Scar tissue size following myocardial infarction is an independent predictor of cardiovascular outcomes, yet little is known about factors regulating scar size. We demonstrate that collagen V, a minor constituent of heart scars, regulates the size of heart scars after ischemic injury. Depletion of collagen V led to a paradoxical increase in post-infarction scar size with worsening of heart function. A systems genetics approach across 100 in-bred strains of mice demonstrated that collagen V is a critical driver of postinjury heart function. We show that collagen V deficiency alters the mechanical properties of scar tissue, and altered reciprocal feedback between matrix and cells induces... 

Background:: Since the cornea is responsible for transmitting and focusing light into the eye, injury or pathology affecting any layer of the cornea can cause a detrimental effect on visual acuity. Aging is also a reason for corneal degeneration. Depending on the level of the injury, conservative therapies and donor tissue transplantation are the most common treatments for corneal diseases. Not only is there a lack of donor tissue and risk of infection/rejection, but the inherent ability of corneal cells and layers to regenerate has led to research in regenerative approaches and treatments. Methods:: In this review, we first discussed the anatomy of the cornea and the required properties for... 

Three-dimensional cell culture and the forming multicellular aggregates are superior over traditional monolayer approaches due to better mimicking of in vivo conditions and hence functions of a tissue. A considerable amount of attention has been devoted to devising efficient methods for the rapid formation of uniform-sized multicellular aggregates. Microfluidic technology describes a platform of techniques comprising microchannels to manipulate the small number of reagents with unique properties and capabilities suitable for biological studies. The focus of this review is to highlight recent studies of using microfluidics, especially droplet-based types for the formation, culture, and... 

This paper presents a bi-directional closed-form analytical solution, in the framework of nonlinear soft composites mechanics, for top-down hyperelastic characterization of brain white matter tissue components, based on the directional homogenized responses of the tissue in the axial and transverse directions. The white matter is considered as a transversely isotropic neo-Hookean composite made of unidirectional distribution of axonal fibers within the extracellular matrix. First, two homogenization formulations are derived for the homogenized axial and transverse shear moduli of the tissue, based on definition of the strain energy density function. Next, the rule of mixtures and... 

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... 

Hypothesis: It is now being increasingly accepted that cells in their native tissue show different morphologies than those grown on a culture plate. Culturing cells on the conventional two-dimensional (2D) culture plates does not closely resemble the in vivo three-dimensional (3D) structure of cells which in turn seems to affect cellular function. This is one of the reasons, among many others, that nanoparticles uptake and toxicology data from 2D culture plates and in vivo environments are not correlated with one another. In this study, we offer a novel platform technology for producing more in vivo-like models of in vitro cell culture. Experiments: The normal fibroblast cells (HU02) were... 

This paper presents a three-dimensional micromechanical model of brain white matter tissue as a transversely isotropic soft composite described by the generalized Ogden hyperelastic model. The embedded element technique, with corrected stiffness redundancy in large deformations, was used for the embedment of a histology-informed probabilistic distribution of the axonal fibers in the extracellular matrix. The model was linked to a multi-objective, multi-parametric optimization algorithm, using the response surface methodology, for characterization of material properties of the axonal fibers and extracellular matrix in an inverse finite element analysis. The optimum hyperelastic... 

High rates of mortality and morbidity stemming from cardiovascular diseases unveil extreme limitations in current therapies despite enormous advances in medical and pharmaceutical sciences. Following myocardial infarction (MI), parts of myocardium undergo irreversible remodeling and is substituted by a scar tissue which eventually leads to heart failure (HF). To address this issue, cardiac patches have been utilized to initiate myocardial regeneration. In this study, a porous cardiac patch is fabricated using a mixture of decellularized myocardium extracellular matrix (ECM) and chitosan (CS). Results of rheological measurements, SEM, biodegradation test, and MTT assay showed that the... 

Cartilage is an avascular tissue with limited self-repair ability. Since the methods for treatment of cartilage defects have not been effective, new therapies based on tissue engineering are considered over the recent years. In this study, human cartilage tissue was decellularized and porous injectable microcarriers (MCs) composed of acellular extracellular matrix (ECM) of cartilage tissue and chitosan (CS), with different ECM weight ratios, were fabricated by electrospraying technique to be used in the treatment of articular cartilage defects. Various properties of ECM/CS MCs such as microstructure, mechanical strength, water uptake behaviour, and biodegradability rate were investigated.... 

Organ-on-chip (OOC) platforms have attracted attentions of pharmaceutical companies as powerful tools for screening of existing drugs and development of new drug candidates. OOCs have primarily used human cell lines or primary cells to develop biomimetic tissue models. However, the ability of human stem cells in unlimited self-renewal and differentiation into multiple lineages has made them attractive for OOCs. The microfluidic technology has enabled precise control of stem cell differentiation using soluble factors, biophysical cues, and electromagnetic signals. This study discusses different tissue- and organ-on-chip platforms (i.e., skin, brain, blood–brain barrier, bone marrow, heart,... 

Interaction between intracellular dynamics and extracellular matrix (ECM) generally occurred into very thin fragment of moving cell, namely lamellipodia, enables all movable cells to crawl on ECM. In fast-moving cells such as fish Keratocytes, Lamellipodia including most cell area finds a fan-like shape during migration, with a variety of aspect ratio function of fish type. In this work, our purpose is to present a novel and more complete two-dimensional continuum mathematical model of actomyosin-cytosolic two-phase flow of a self-deforming Keratocyte with circular spreaded to steady fan-like shape. In the new approach, in addition to the two-phase flow of the F-actin and cytosol, the... 

Due to the avascular nature of articular cartilage, damaged tissue has little capacity for spontaneous healing. Three-dimensional scaffolds have potential for use in tissue engineering approach for cartilage repair. In this study, bovine cartilage tissue was decellularized and chemically crosslinked hybrid chitosan/extracellular matrix (ECM) scaffolds were fabricated with different ECM weight ratios by simple freeze drying method. Various properties of chitosan/ECM scaffolds such as microstructure, mechanical strength, swelling ratio, and biodegradability rate were investigated to confirm improved structural and biological characteristics of chitosan scaffolds in the presence of ECM. The... 

Nanofibrous structures that mimic the native extracellular matrix and promote cell adhesion have attracted considerable interest for biomedical applications. In this study, GO-modified nanofibrous biopolymers (GO) were prepared by electrospinning blended solutions of chitosan (80 vol%), polyvinyl pyrrolidone (15 vol%), polyethylene oxide (5 vol%) containing GO nanosheets (0–2 wt%). It is shown that GO nanosheets significantly change the conductivity and viscosity of highly concentrated chitosan solutions, so that ultrafine and uniform fibers with an average diameter of 60 nm are spinnable. The GO-reinforced nanofibers with controlled pore structure exhibit enhanced elastic modulus and...