Sharif Digital Repository

Many potential therapies are currently being studied that may promote neural regeneration and guide regenerating axons to form correct connections following injury. It has been shown that adult neurons have some limited regenerative capabilities, and the lack of connection formation between neurons is not an intrinsic inability of these cells to form axons after being damaged, but rather the inhibitory microenvironment of the injured tissue prevents regeneration. In this study, the polarization and chemotaxis of neuronal stem cells (NSC) in response to quantified gradients of nerve growth factor (NGF) was examined. To accomplish this, a microfluidic device was designed and fabricated to... 

Graphene oxide foam (GOF) layers with thicknesses of ∼15-50 μm and density of ∼10 graphene oxide (GO) sheets/μm were fabricated by precipitation of chemically exfoliated GO sheets in an aqueous suspension at ∼80 °C under UV irradiation. Then, rolled GOFs with desirable scales were developed as electrically conductive 3D-scaffolds and applied in directional growth of neural fibers, through differentiation of human neural stem cells (hNSCs) into neurons under an electrical stimulation. X-ray photoelectron spectroscopy indicated that the UV irradiation resulted in partial deoxygenation of the layers. Scanning electron microscopy and Raman spectroscopy confirmed the presence of multilayer GO... 

Ground-state pluripotency is a cell state in which pluripotency is established and maintained through efficient repression of endogenous differentiation pathways. Self-renewal and pluripotency of embryonic stem cells (ESCs) are influenced by ESC-associated microRNAs (miRNAs). Here, we provide a comprehensive assessment of the “miRNome” of ESCs cultured under conditions favoring ground-state pluripotency. We found that ground-state ESCs express a distinct set of miRNAs compared with ESCs grown in serum. Interestingly, most “ground-state miRNAs” are encoded by an imprinted region on chromosome 12 within the Dlk1-Dio3 locus. Functional analysis revealed that ground-state miRNAs embedded in the... 

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... 

Peripheral nerve injuries remain among the most challenging medical issues despite numerous efforts to devise methods in fabrication of nerve conduits to functionally regenerate axonal defects. In this regard, the current study offers a holistic perspective in design by considering the mechanical, topographical and structural aspects which are crucial for a successful nerve guide conduit. Poly(e-caprolactone) and gelatin were employed to serve this purpose in the form of dual-electrospun films which were rolled and later shaped the assembly of a multichannel conduit. Polyaniline/graphene (PAG) nanocomposite was incorporated to endow the conduit with conductive properties. FTIR analysis,... 

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... 

A series of herbal extract incorporated into poly(lactic acid) (PLA) composite nanofibrous scaffolds were successfully prepared by using electrospinning technique. Equisetum arvense extract (EE) and nanohydroxyapatite (nHA) in different quantities were loaded into PLA solution to fabricate composite nanofibrous webs under various electrospinning conditions. Uniform nanofibers were obtained with an average diameter of 157 ± 47 nm in the case of those containing the herbal extract. Characterization of the webs was carried out by means of Fourier transform infrared (FTIR) spectroscopy, field emission-scanning electron microscopy (FESEM), energy-dispersive X-ray spectroscopy (EDX), and... 

In order to regenerate bone defects, bioactive hierarchically scaffolds play a key role due to their multilevel porous structure, high surface area, enhanced nutrient transport and diffusion. In this study, novel hierarchically porous silk fibroin (SF) and silk fibroin-bioactive glass (SF-BG) composite were fabricated with controlled architecture and interconnected structure, by combining indirect three-dimensional (3D) inkjet printing and freeze-drying methods. Further, the effect of 45S5 Bioactive glass particles of different sizes (<100 nm and 6 μm) on mechanical strength and cell behavior was investigated. The results demonstrated that the hierarchical structure in this scaffold was... 

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... 

Reduced graphene oxide nanoplatelets (rGONPs) were synthesized by sonication of covalently PEGylated GO sheets followed by a chemical reduction using hydrazine and bovine serum albumin. Human mesenchymal stem cells (hMSCs), as a fundamental factor in tissue engineering, were isolated from umbilical cord blood (as a recently proposed source for extracting fresh hMSCs) to investigate, for the first time, the size-dependent cyto- and geno-toxic effects of the rGONPs on the cells. The cell viability test showed significant cell destructions by 1.0 μg/mL rGONPs with average lateral dimensions (ALDs) of 11±4 nm, while the rGO sheets with ALDs of 3.8±0.4 μm could exhibit a significant cytotoxic... 

Reduced graphene oxide nanomeshes (rGONMs), as p-type semiconductors with band-gap energy of ~1. eV, were developed and applied in near infrared (NIR) laser stimulation of human neural stem cells (hNSCs) into neurons. The biocompatibility of the rGONMs in growth of hNSCs was found similar to that of the graphene oxide (GO) sheets. Proliferation of the hNSCs on the GONMs was assigned to the excess oxygen functional groups formed on edge defects of the GONMs, resulting in superhydrophilicity of the surface. Under NIR laser stimulation, the graphene layers (especially the rGONMs) exhibited significant cell differentiations, including more elongations of the cells and higher differentiation of... 

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 this study, lyophilized advanced platelet rich fibrin (A-PRF) was used in combination with collagen-chitosan membrane for the first time to combine advantages of both collagen and A-PRF membranes. Response surface methodology (RSM) was used to design the experimental condition and to correlate the effects of parameters, including chitosan/collagen (chit/col) weight ratio and A-PRF concentration on Young's modulus, mesenchymal stem cell (MSCs) viability and degradation rate of the membranes. Results showed that Young's modulus of the membranes was intensified by increasing chit/col weight ratio and decreasing A-PRF concentration from 3 to 8 MPa. Cell viability of MSCs was improved by both... 

Background: Human papillomavirus (HPV)-associated malignancy remain a main cause of cancer in men and women. Cancer immunotherapy has represented great potential as a new promising cancer therapeutic approach. Here, we report Mesenchymal stem cells (MSCs) as a carrier for the delivery of oncolytic Newcastle disease virus (NDV) for the treatment of HPV-associated tumor. Methods: For this purpose, MSCs obtained from the bone marrow of C57BL mice, then cultured and characterized subsequently by the flow cytometry analysis for the presence of cell surface markers. In this study, we sought out to determine the impacts of MSCs loaded with oncolytic NDV on splenic T cell and cytokine immune... 

Graphene, a two-dimensional (2D) sheet of sp2-hybridized carbon atoms packed into a honeycomb lattice, has led to an explosion of interest in the field of materials science, physics, chemistry, and biotechnology since the few-layers graphene (FLG) flakes were isolated from graphite in 2004. For an extended search, derivatives of nanomedicine such as biosensing, biomedical, antibacterial, diagnosis, cancer and photothermal therapy, drug delivery, stem cell, tissue engineering, imaging, protein interaction, DNA, RNA, toxicity, and so on were also added. Since carbon nanotubes are normally described as rolled-up cylinders of graphene sheets and the controllable synthesis of nanotubes is well... 

Microfluidic devices have received wide attention and shown great potential in the field of tissue engineering and regenerative medicine. Investigating cell response to various stimulations is much more accurate and comprehensive with the aid of microfluidic devices. In this study, we introduced a microfluidic device by which the matrix density as a mechanical property and the concentration profile of a biochemical factor as a chemical property could be altered. Our microfluidic device has a cell tank and a cell culture chamber to mimic both 2D to 3D and 3D to 3D migration of three types of cells. Fluid shear stress is negligible on the cells and a stable concentration gradient can be... 

Harnessing neural stem cells to repair neuronal damage is a promising potential treatment for neuronal diseases. To enable future therapeutic efficacy, the survival, proliferation, migration and differentiation of neural stem/progenitor cells (NPCs) should be accurately studied and optimized in in vitro platforms before transplanting these cells into the body for treatment purposes. Such studies can determine the appropriate quantities of the biochemical and biomechanical factors needed to control and optimize NPC behavior in vivo. In this study, NPCs were cultured within a microfluidic device while being encapsulated within the collagen matrix. The migration and differentiation of NPCs were... 

In this study, the Lattice Boltzmann Method (LBM) is used to investigate the deformation of two droplets within microfluidic T-junctions (MFTD). In order to increase the accuracy the two immiscible fluids are modeled using the He-Chen-Zhang model. First, this model is applied to ensure that the surface tension effect existing between the droplets and the continuous fluid is properly implemented in the model. Then the collision and merging of the two droplets within the intersection of a T-shaped microchannel is investigated. For generating droplet formation the effects of relevant dimensionless parameters such as the Reynolds, the Weber numbers as well as a collision parameter affecting the... 

Modern techniques for expanding stem cells play a substantial role in tissue engineering: the raw material that facilitates regeneration of damaged tissues and treats diseases. The environmental conditions and bioprocessing methods are the primary determinants of the rate of cultured stem cell proliferation. Bioceramic scaffolds made of calcium phosphate are effective substrates for optimal cell proliferation. The present study investigates the effects of two bioceramic scaffolds on proliferating cells in culture media. One scaffold was made of hydroxyapatite and the other was a mixture of hydroxyapatite and ferromagnetic material (Fe3O4 nanoparticles). Disk-shaped (10 mm × 2 mm) samples of...