Sharif Digital Repository

Animal models and traditional cell cultures are essential tools for drug development. However, these platforms can show striking discrepancies in efficacy and side effects when compared to human trials. These differences can lengthen the drug development process and even lead to drug withdrawal from the market. The establishment of preclinical drug screening platforms that have higher relevancy to physiological conditions is desirable to facilitate drug development. Here, a heart-on-a-chip platform, incorporating microgrooves and electrical pulse stimulations to recapitulate the well-aligned structure and synchronous beating of cardiomyocytes (CMs) for drug screening, is reported. Each chip... 

Breast cancer is the most common invasive cancer in women and the second leading cause of cancer death in women after lung cancer. The purpose of this study is a targeted delivery toward in vitro (on MCF7 and 4T1 breast cancer cell lines) through niosomes-based nanocarriers. To this end, different bioactive molecules, including hyaluronic acid (HA), folic acid (FA), and polyethylene glycol (PEG), were used and compared for surface modification of niosomes to enhance endocytosis. FA-functionalized niosomes (Nio/5-FU/FA) were able to increase cell cytotoxicity and reduce cell migration and invasion compared to PEG-functionalized niosomes (Nio/5-FU/PEG), and HA-functionalized niosomes... 

Sulfur quantum dots (SQDs) were fabricated using a facile hydrothermal method and used for the preparation of functional food packaging film and compared the properties with other sulfur-based fillers like elemental sulfur (ES) and sulfur nanoparticles (SNP). The SQDs have an average size of 5.3 nm and were very stable in aqueous suspension. Unlike other sulfur-based fillers, the SQD showed high antioxidant, antibacterial and antifungal activity, but no cytotoxicity was found for L929 mouse fibroblasts even after long-term exposure of 48 h. When sulfur-based fillers were added to the alginate film, SQD was more evenly dispersed in the polymer matrix than SNP and ES. The addition of SQD to... 

Background: This research follows some investigations through neural tissue engineering, including fabrication, surface treatment, and evaluation of novel self-stimuli conductive biocompatible and degradable nanocomposite scaffolds. Methods: Gelatin as a biobased material and polyvinylidene fluoride (PVDF) as a mechanical, electrical, and piezoelectric improvement agent were co-electrospun. In addition, polyaniline/graphene (PAG) nanoparticles were synthesized and added to gelatin solutions in different percentages to induce electrical conductivity. After obtaining optimum PAG percentage, cold atmospheric plasma (CAP) treatment was applied over the best samples by different plasma variable... 

Nanomedicine has seen a significant rise in the development of new research tools and clinically functional devices. In this regard, significant advances and new commercial applications are expected in the pharmaceutical and orthopedic industries. For advanced orthopedic implant technologies, appropriate nanoscale surface modifications are highly effective strategies and are widely studied in the literature for improving implant performance. It is well-established that implants with nanotubular surfaces show a drastic improvement in new bone creation and gene expression compared to implants without nanotopography. Nevertheless, the scientific and clinical understanding of mixed oxide... 

Nanomedicine has seen a significant rise in the development of new research tools and clinically functional devices. In this regard, significant advances and new commercial applications are expected in the pharmaceutical and orthopedic industries. For advanced orthopedic implant technologies, appropriate nanoscale surface modifications are highly effective strategies and are widely studied in the literature for improving implant performance. It is well-established that implants with nanotubular surfaces show a drastic improvement in new bone creation and gene expression compared to implants without nanotopography. Nevertheless, the scientific and clinical understanding of mixed oxide... 

Chinese hamster ovary cells are the main cellular factories for production of a wide range of recombinant proteins in biopharmaceutical industry. Recombinant human Interferon beta-1a (rh-IFN β-1a), as a cytokine is broadly used to treat multiple sclerosis. In this work, the cell line producing rh-IFN β-1a was studied to improve cell density along with the specific expression. For this reason different cell culture experiments were done using different commercial serum-free media to find the appropriate media providing higher cell density. It was shown DMEMF12, DMEM:ProCHO5, and CHO-S-SFM II led to higher cell density and shorter doubling time. Next, using these media, fed-batch, and... 

miR-29b2 and miR-29c play a suppressive role in breast cancer progression. C1orf132 (also named MIR29B2CHG) is the host gene for generating both microRNAs. However, the region also expresses longer transcripts with unknown functions. We employed bioinformatics and experimental approaches to decipher C1orf132 expression and function in breast cancer tissues. We also used the CRISPR/Cas9 technique to excise a predicted C1orf132 distal promoter and followed the behavior of the edited cells by real-time PCR, flow cytometry, migration assay, and RNA-seq techniques. We observed that C1orf132 long transcript is significantly downregulated in triple-negative breast cancer. We also identified a... 

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, physically cross-linked hydrogels were developed by freezing-thawing method while different concentrations of honey were included into the hydrogels for accelerated wound healing. The hydrogel was composed of chitosan, polyvinyl alcohol (PVA), and gelatin with the ratio of 2:1:1 (v/v), respectively. Further, the effect of honey concentrations on antibacterial properties, and cell behavior was investigated. In vivo studies, including wound healing mechanism using rat model and histological analysis of section tissue samples were performed. The results illustrated that the incorporation of honey in hydrogels increased the ultimate strain of hydrogels approximately two times,... 

Naïve pluripotency can be established in human pluripotent stem cells (hPSCs) by manipulation of transcription factors, signaling pathways, or a combination thereof. However, differences exist in the molecular and functional properties of naïve hPSCs generated by different protocols, which include varying similarities with pre-implantation human embryos, differentiation potential, and maintenance of genomic integrity. We show here that short treatment with two chemical agonists (2a) of nuclear receptors, liver receptor homologue-1 (LRH-1) and retinoic acid receptor gamma (RAR-γ), along with 2i/LIF (2a2iL) induces naïve-like pluripotency in human cells during reprogramming of fibroblasts,... 

In this study, polyvinyl alcohol hydrogel chains were crosslinked by polyurethane in order to synthesize a suitable substrate for cartilage lesions. The substrate was fully characterized, and in vitro and in vivo investigations were conducted based on a sheep model. In vitro tests were performed based on the chondrocyte cells with the Alcian Blue and safranin O staining in order to prove the presence of proteoglycan on the surface of the synthesized substrate, which has been secreted by cultures of chondrocytes. Furthermore, the expression of collagen type I, collagen type II, aggrecan, and Sox9 was presented in the chondrocyte cultures on the synthesized substrate through RT-PCR. In... 

Cervical cancer is the second-most-common cause of malignancies in women worldwide, and the oncogenic activity of the human papilloma virus types (HPV) E7 protein has a crucial role in anogenital tumors. In this study, we have designed a therapeutic vaccine based on chitosan nanodelivery systems to deliver HPV-16 E7 DNA vaccine, considered as a tumor specific antigen for immunotherapy of HPV-associated cervical cancer. We have developed a Nano-chitosan (NCS) as a carrier system for intramuscular administration using a recombinant DNA vaccine expressing HPV-16 E7 (NCS-DNA E7 vaccine). NCS were characterized in vitro for their gene transfection ability. Results: The transfection of CS-pEGFP... 

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... 

A single step supercritical method was introduced for synthesis of “magnetite - reduced graphene oxide (M-rGO)” composite in supercritical methanol. Modified surface, smaller size, lesser cytotoxicity, and homogenous dispersion of Fe3O4 nanoparticles on the graphene surface were advantages of this new M-rGO composite in comparison to the materials synthesized by conventional wet chemical method (M-GO). Nanocomposites were injected in tissue equivalent phantoms of agarose gel in 10 mg/g dosage, and were irradiated by a 1600 mW laser beam at wavelength of 800–810 nm. The M-rGO and M-GO were found to be the most and the least efficient samples for increasing the temperature of the phantom. As... 

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... 

Coaxial electrospinning with the ability to use simultaneously two separate solvents provides a promising strategy for drug delivery. Nevertheless, controlled release of hydrophilic and sensitive therapeutics from slow biodegradable polymers is still challenging. To address this gap, we fabricated core-sheath fibers for dual delivery of lysozyme, as a model protein, and phenytoin sodium as a small therapeutic molecule. The sheath was processed by a gelatin solution while the core fibers were fabricated from an aqueous gelatin/PVA solution. Microstructural studies by transmission and scanning electron microscopy reveal the formation of homogeneous core-sheath nanofibers with an outer and... 

The synthesis of a new drug delivery system based on hybrid nanomaterials containing a β-CD core and hyperbranched PG is described. Conjugating PG branches onto β-CD not only increases its water solubility but also affects its host/guest properties deeply. It can form molecular inclusion complexes with small hydrophobic guest molecules such as ferrocene or FITC with reasonable release. In addition, the achievable payloads are significantly higher as for carriers such as hyperbranched PGs. Short-term in vitro cytotoxicity and hemocompatibility tests on L929 cell lines show that the hybrid nanomaterial is highly biocompatible. Due to their outstanding properties, β-CD-g-PG hybrid nanomaterials...