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... 

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... 

Design and development of biodegradable scaffolds with highly uniform and controlled internal structure that stimulate tissue regeneration are the focus of many studies. The aim of this work is to apply a modified three-dimensional (3D) printing process to fabricate polymer-matrix composites with controlled internal architecture. Computationally-designed plaster molds with various pore sizes in the range of 300-800. μm were prepared by employing 3D printing of a water-based binder. The molds were converted to ε-polycaprolactone (PCL) and PCL/bioactive glass (BG) composite scaffolds by solvent casting and freeze drying methods. Optical and electron microscopy studies revealed that the pore... 

This review aims to propose the integrative implementation of microfluidic devices, biomaterials, and computational methods that can lead to a significant progress in tissue engineering and regenerative medicine researches. Simultaneous implementation of multiple techniques can be very helpful in addressing biological processes. Providing controllable biochemical and biomechanical cues within artificial extracellular matrix similar to in vivo conditions is crucial in tissue engineering and regenerative medicine researches. Microfluidic devices provide precise spatial and temporal control over cell microenvironment. Moreover, generation of accurate and controllable spatial and temporal... 

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... 

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... 

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... 

Employing of the composite electrospun scaffold containing herbal extract in conjugation with co-culturing of cells can open up new window to the design of efficient biomaterials for skin tissue regeneration. Here, we introduce the synergistic effect of composite electrospun nanofibrous scaffold of nylon66 loaded with Beta vulgaris (B. vulgaris) (extract of beet roots, a plants whose widely used in Iranian folk medicine as wound healing medicine) and co-culture of mesenchymal stem-cells (MSCs)-human keratinocyte (H-keratino) differentiation towards epithelial lineage. In vitro biocompatibility was examined through MTT assay and epithelial differentiation checked by real-time PCR and... 

Chronic, non-healing wounds place a significant burden on patients and healthcare systems, resulting in impaired mobility, limb amputation, or even death. Chronic wounds result from a disruption in the highly orchestrated cascade of events involved in wound closure. Significant advances in our understanding of the pathophysiology of chronic wounds have resulted in the development of drugs designed to target different aspects of the impaired processes. However, the hostility of the wound environment rich in degradative enzymes and its elevated pH, combined with differences in the time scales of different physiological processes involved in tissue regeneration require the use of effective drug... 

According to the latest report from the World Health Organization, an estimated 265,000 deaths still occur every year as a direct result of burn injuries. A widespread range of these deaths induced by burn wound happens in low- and middle-income countries, where survivors face a lifetime of morbidity. Most of the deaths occur due to infections when a high percentage of the external regions of the body area is affected. Microbial nutrient availability, skin barrier disruption, and vascular supply destruction in burn injuries as well as systemic immunosuppression are important parameters that cause burns to be susceptible to infections. Topical antimicrobials and dressings are generally... 

Keratinocyte Growth Factor (KGF) is a paracrine-acting, epithelial mitogen that plays a prominent role in the regeneration of damaged epithelial tissues. In spite of different attempts to produce recombinant human KGF in many organisms, including bacteria, mammalian cells, plant cells and insect cells; production of recombinant form suffers from lower yields and recovery relative to other recombinant proteins of similar size and properties. Due to many advantages of Pichia pastoris expression systems for producing industrial enzymes and pharmaceutical proteins, in this study P. pastoris was chosen as a host for KGF expression. For preparing human KGF coding sequence, MCF-7 cell line was... 

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... 

Skeletal muscle tissue engineering aims to fabricate tissue constructs to replace or restore diseased or injured skeletal muscle tissues in the body. Several biomaterials and microscale technologies have been used in muscle tissue engineering. However, it is still challenging to mimic the function and structure of the native muscle tissues. Three-dimensional (3D) bioprinting is a powerful tool to mimic the hierarchical structure of native tissues. Here, 3D bioprinting was used to fabricate tissue constructs using gelatin methacryloyl (GelMA)-alginate bioinks. Mechanical and rheological properties of GelMA-alginate hydrogels were characterized. C2C12 myoblasts at the density 8 × 106 cells/mL... 

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... 

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,... 

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... 

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... 

Abstract: 3D bioprinting technology is a promising approach for corneal stromal tissue regeneration. In this study, gelatin methacrylate (GelMA) mixed with corneal stromal cells was used as a bioink. The visible light-based stereolithography (SLA) 3D bioprinting method was utilized to print the anatomically similar dome-shaped structure of the human corneal stroma. Two different concentrations of GelMA macromer (7.5 and 12.5%) were tested for corneal stroma bioprinting. Due to high macromer concentrations, 12.5% GelMA was stiffer than 7.5% GelMA, which made it easier to handle. In terms of water content and optical transmittance of the bioprinted scaffolds, we observed that scaffold with... 

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... 

In this study, the in-vitro bone regeneration ability of commercial pure titanium (CP-Ti) surface modified via electrospun polyvinylidene/hydroxyapatite (PVP/HA) masking and subsequent Nd-YAG pulsed laser treatment was investigated. The ratio of HA to PVP played a significant role in achieving a perfect homogenous mask on the CP-Ti. In the laser treatment process, the parameter of area scanning speed (ASS) had an important influence on the final surface morphology. A favorable range was defined for this parameter where these two conditions were satisfied: no PVP remaining and no severe substrate melting. Within a favorable range of ASS, as decreasing ASS exchanged the surface structure from...