Sharif Digital Repository

Tissue engineering and regenerative medicine have solved numerous problems related to the repair and regeneration of damaged organs and tissues arising from aging, illnesses, and injuries. Nanotechnology has further aided tissue regeneration science and has provided outstanding opportunities to help disease diagnosis as well as treat damaged tissues. Based on the most recent findings, magnetic nanostructures (MNSs), in particular, have emerged as promising materials for detecting, directing, and supporting tissue regeneration. There have been many reports concerning the role of these nano-building blocks in the regeneration of both soft and hard tissues, but the subject has not been... 

Overexpression of proteins/antigens and other gene-related sequences in the bodies could lead to significant mutations and refractory diseases. Detection and identification of assorted trace concentrations of such proteins/antigens and/or gene-related sequences remain challenging, affecting different pathogens and making viruses stronger. Correspondingly, coronavirus (SARS-CoV-2) mutations/alterations and spread could lead to overexpression of ssDNA and the related antigens in the population and brisk activity in gene-editing technologies in the treatment/detection may lead to the presence of pCRISPR in the blood. Therefore, the detection and evaluation of their trace concentrations are of... 

Here we report on the development of a hybrid nanofibrous scaffold made from polyvinylidene fluoride (PVDF) nanofibers embedding zinc oxide nanorods (ZnOns), and poly(ε-caprolactone) (PCL) nanofibers incorporating dexamethasone (DEX)-loaded chitosan nanoparticles using dual-electrospinning method. Fourier transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), scanning electron microscopy (SEM), and tensile analysis were carried out for physiochemical characterization of the scaffolds, followed by DEX release profile. In addition, an MTT assay was conducted to assess the viability of mouse bone marrow-derived mesenchymal stem cells (mBMSCs) on the hybrid nanofibrous scaffold.... 

Multi-walled carbon nanotubes (MWCNTs) are one of the preferred candidates for reinforcing polymeric nanobiocomposites, such as acrylic bone type of cement. In this study, at first, bulk samples of the reinforced polymethylmethacrylate (PMMA) matrix were prepared with 0.1, 0.25, and 0.5 wt per wt% of MWCNTs by the casting method. Tensile and three-point bending tests were performed to determine the essential mechanical properties of bone cement, such as tensile and bending strengths. The tensile fracture surfaces were investigated by scanning electron microscopy (SEM). The commercial software (Abaqus) was used to conduct finite element analysis (FEA) by constructing a representative volume... 

The employment of tissue engineering scaffolds in the reconstruction of the damaged bone tissues has shown remarkable promise since they significantly facilitate the healing process. Fabrication of highly porous biocompatible scaffolds with sufficient mechanical strength is still challenging. In this regard, polymers have been widely utilized to construct three-dimensional (3D) porous scaffolds due to their excellent processability and biocompatibility. However, insufficient mechanical strength and inappropriate degradation rate of the monophasic polymer scaffolds in the bone regeneration process, as the main challenges, limit their extensive clinical application. The incorporation of... 

Cancer has long been a leading cause of death. The primary tumor, however, is not the main cause of death in more than 90% of cases. It is the complex process of metastasis that makes cancer deadly. The invasion metastasis cascade is the multi-step biological process of cancer cell dissemination to distant organ sites and adaptation to the new microenvironment site. Unraveling the metastasis process can provide great insight into cancer death prevention or even treatment. Microfluidics is a promising platform, that provides a wide range of applications in metastasis-related investigations. Cell culture microfluidic technologies for in vitro modeling of cancer tissues with fluid flow and the... 

We report a chitosan-based nanocomposite thermogel with superior shear modulus resembling that of cartilage and dual pro-chondrogenic and anti-inflammatory functions. Two therapeutic agents, kartogenin (KGN) and diclofenac sodium (DS), are employed to promote chondrogenesis of stem cells and suppress inflammation, respectively. To extend the release time in a controlled manner, KGN is encapsulated in the uniform-sized starch microspheres and DS is loaded into the halloysite nanotubes. Both drug carriers are doped into the maleimide-modified chitosan hydrogel to produce a shear modulus of 167 ± 5 kPa that is comparable to that of articular cartilage (50–250 kPa). Owing to the hydrogel... 

Introduction: B lymphocyte-induced maturation protein 1 (BLIMP1) encoded by the positive regulatory domain 1 gene (PRDM1), is a key regulator in T cell differentiation in mouse models. BLIMP1-deficiency results in a lower effector phenotype and a higher memory phenotype. Methods: In this study, we aimed to determine the role of transcription factor BLIMP1 in human T cell differentiation. Specifically, we investigated the role of BLIMP1 in memory differentiation and exhaustion of human T cells. We used CRISPR interference (CRISPRi) to knock-down BLIMP1 and investigated the differential expressions of T cell memory and exhaustion markers in BLIMP1-deficient T cells in comparison with... 

A proper self-regenerating capability is lacking in human cardiac tissue which along with the alarming rate of deaths associated with cardiovascular disorders makes tissue engineering critical. Novel approaches are now being investigated in order to speedily overcome the challenges in this path. Tissue engineering has been revolutionized by the advent of nanomaterials, and later by the application of carbon-based nanomaterials because of their exceptional variable functionality, conductivity, and mechanical properties. Electrically conductive biomaterials used as cell bearers provide the tissue with an appropriate microenvironment for the specific seeded cells as substrates for the sake of... 

Stem cell therapy has been introduced as an emerging approach for injured tissue regeneration. This chapter addresses developing regenerative medicine techniques for controlling stem cell behavior. Recent studies have been reviewed and novel approaches have been divided into four main categories: 3D bioprinting, lithography, microfluidics, and electrospinning. Moreover, the impact of applied biophysical and/or biochemical cues to the designed scaffold on controlling stem cell activity has been discussed. The potential of using stem cells for various soft and hard tissue regenerations has been explored in different bioengineered scaffolds and the applied techniques for controlling stem cell... 

One of the most arduous challenges in tissue engineering is neovascularization, without which there is a lack of nutrients delivered to a target tissue. Angiogenesis should be completed at an optimal density and within an appropriate period of time to prevent cell necrosis. Failure to meet this challenge brings about poor functionality for the tissue in comparison with the native tissue, extensively reducing cell viability. Prior studies devoted to angiogenesis have provided researchers with some biomaterial scaffolds and cell choices for angiogenesis. For example, while most current angiogenesis approaches require a variety of stimulatory factors ranging from biomechanical to biomolecular... 

Microfluidics is a promising approach for the facile and large-scale fabrication of monodispersed droplets for various applications in biomedicine. This technology has demonstrated great potential to address the limitations of regenerative medicine. Microfluidics provides safe, accurate, reliable, and cost-effective methods for encapsulating different stem cells, gametes, biomaterials, biomolecules, reagents, genes, and nanoparticles inside picoliter-sized droplets or droplet-derived microgels for different applications. Moreover, microenvironments made using such droplets can mimic niches of stem cells for cell therapy purposes, simulate native extracellular matrix (ECM) for tissue... 

Neurological diseases have different etiological causes. Contemporary, developing an ef-fective treatment for these diseases is an ongoing challenge. Cell therapy is recognized as one of the promising solutions for the treatment of these diseases. Amongst various types of stem cells, bone marrow-derived mesenchymal stem cells (BM-MSC) are known to be the most widely used stem cells. These cells are endowed with appealing properties such as the ability to differentiate into other cell types, including the muscle, liver, glial, and nerve cells. In this review study, we have systematically evaluated the ability of a variety of chemical compounds used in the last ten years to differentiate... 

Background: The exact pathogenic mechanism causes hair miniaturization during androgenic alopecia (AGA) has not been delineated. Recent evidence has shown a role for non-coding regulatory RNAs, such as microRNAs (miRNAs), in skin and hair disease. There is no reported information about the role of miRNAs in hair epithelial cells of AGA. Objectives: To investigate the roles of miRNAs affecting AGA in normal and patient's epithelial hair cells. Methods: Normal follicular stem and progenitor cells, as well as follicular patient's stem cells, were sorted from hair follicles, and a miRNA q-PCR profiling to compare the expression of 748 miRNA (miRs) in sorted cells were performed. Further, we... 

For bone tissue engineering, stem cell‐based therapy has become a promising option. Re-cently, cell transplantation supported by polymeric carriers has been increasingly evaluated. Herein, we encapsulated human olfactory ectomesenchymal stem cells (OE‐MSC) in the collagen hydrogel system, and their osteogenic potential was assessed in vitro and in vivo conditions. Col-lagen type I was composed of four different concentrations of (4 mg/mL, 5 mg/mL, 6 mg/mL, 7 mg/mL). SDS‐Page, FTIR, rheologic test, resazurin assay, live/dead assay, and SEM were used to characterize collagen hydrogels. OE‐MSCs encapsulated in the optimum concentration of collagen hydrogel and transplanted in rat calvarial... 

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... 

Limited regeneration capacity of cartilage can be addressed by tissue engineering approaches including localized delivery of bioactive agents using biomaterials. Although chitosan hydrogels have been considered as appropriate candidates for these purposes, however, their poor mechanical properties limit their real applications. Here, we develop in situ forming chitosan hydrogels with enhanced shear modulus by chemical modification of chitosan using N-(β-maleimidopropyloxy) succinimide ester (BMPS). Moreover, we utilize β-Glycerophosphate (β-GP) in the hydrogels for achieving thermosensitivity. We investigate the effects of BMPS, β-GP and chitosan concentration on rheological and swelling... 

In the article, a bilayer nanocomposite scaffold made of oxidized alginate (OAL), gelatin (G), and silk fibroin (SF) has been prepared via combining electrospinning, in situ gas foaming, in situ crosslinking and freeze drying methods. The physicochemical and mechanical properties, as well as thermal stability of the proposed composite, have been investigated by SEM, FTIR, XRD, tensile, and TGA analysis. The data indicate that structure and degree of crosslinking play a vital role in adjusting the physical and mechanical properties of composite scaffolds. Further, the authors find a favorable adipose-derived mesenchymal stem cell's (AMSC) attachment and distribution within this novel... 

This study aims to 3D print titanium alloy constructs incorporating gradient of porosities, from the fully dense core to the porous outer surface. Gradient porous specimens were prepared using selective laser melting (SLM). Fully dense specimens fabricated by SLM were used as the control group. Characterization of samples was done using X-ray tomography, uniaxial compression testing, and optical and scanning electron microscopes. The biocompatibility of fabricated samples was investigated using human periodontal ligament stem cells via assessment of cell attachment, viability, and proliferation by direct and indirect assays. The data were analyzed using ANOVA and Tukey’s post hoc test.... 

Microfluidic droplet generators excel in generating monodisperse micrometer-sized droplets and particles. However, the low throughput of conventional droplet generators hinders their clinical and industrial translation. Current approaches to parallelize microdevices are challenged by the two-dimensional nature of the standard fabrication methods. Here, we report the facile production of three-dimensionally (3D) parallelized microfluidic droplet generators consisting of stacked and radially multiplexed channel designs. Computational fluid dynamics simulations form the design basis for a microflow distributor that ensures similar flow rates through all droplet generators. Stereolithography is...