Sharif Digital Repository

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... 

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... 

Though wound healing process is well-researched, this area is poorly known. One reason is that all interactions have not been discovered, the main reason, though, is that the involved processes interact in a very complicated manner with nonlinear feedback. Such complex feedback mechanisms can be easily addressed by mathematical modeling. This paper contains a review of the mathematical modeling of cell interaction with extracellular matrix components during the process of dermal wound healing with focusing on remodeling phase. The models are of partial differential equation type and solved by finite element method. © 2009 IEEE  

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... 

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... 

In this paper, a micromechanical model for connective soft tissues based on the available histological evidences is developed. The proposed model constituents i.e. collagen fibers and ground matrix are considered as hyperelastic materials. The matrix material is assumed to be isotropic Neo-Hookean while the collagen fibers are considered to be transversely isotropic hyperelastic. In order to take into account the effects of tissue structure in lower scales on the macroscopic behavior of tissue, a strain energy density function (SEDF) is developed for collagen fibers based on tissue hierarchical structure. Macroscopic response and properties of tissue are obtained using the numerical... 

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... 

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,... 

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... 

The paucity of cellular and molecular signals essential for normal wound healing makes severe dermatological ulcers stubborn to heal. The novel strategies of skin regenerative treatments are focused on the development of biologically responsive scaffolds accompanied by cells and multiple biomolecules resembling structural and biochemical cues of the natural extracellular matrix (ECM). Electrospun nanofibrous scaffolds provide similar architecture to the ECM leading to enhancement of cell adhesion, proliferation, migration and neo tissue formation. This Review surveys the application of biocompatible natural, synthetic and composite polymers to fabricate electrospun scaffolds as skin... 

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... 

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... 

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... 

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... 

Controlling topographic features at all length scales is of great importance for the interaction of cells with tissue regenerative materials. We utilized an indirect three-dimensional printing method to fabricate polymeric scaffolds with pre-defined and controlled external and internal architecture that had an interconnected structure with macro- (400-500 μm) and micro- (∼25 μm) porosity. Polycaprolactone (PCL) was used as model system to study the kinetics of tissue growth within porous scaffolds. The surface of the scaffolds was decorated with TiO2 and bioactive glass (BG) nanoparticles to the better match to nanoarchitecture of extracellular matrix (ECM). Micrometric BG particles were...