Sharif Digital Repository

This study proposes a mathematical model to evaluate the impact of oxygen carriers and scaffold geometry on oxygen distribution and cell growth in a 3D cardiac construct using computational fluid dynamics (CFD). Flow equations, oxygen balance equation and cell balance equation were solved using special initial and boundary conditions. The modeling results revealed that 55% increase in cardiac cell density occurred by using 6.4% perfluorocarbon oxygen carrier (PFC) compared to pure culture medium without PFC supplementation. Moreover, the effects of the scaffold geometry on cell density were examined by changing the channel numbers and the construct length. A 30% increase in the average cells... 

Nanofibrous structures mimicking the native extracellular matrix have attracted considerable attention for biomedical applications. The present study aims to design and produce drug-eluting core-shell fibrous scaffolds for wound healing and skin tissue engineering. Aloe vera extracts were encapsulated inside polymer fibers containing chitosan, polycaprolactone, and keratin using the co-axial electrospinning technique. Electron microscopic studies show that continuous and uniform fibers with an average diameter of 209 ± 47 nm were successfully fabricated. The fibers have a core-shell structure with a shell thickness of about 90 nm, as confirmed by transmission electron microscopy. By... 

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... 

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... 

Understanding the foreign body response (FBR) and desiging strategies to modulate such a response represent a grand challenge for implant devices and biomaterials. Here, the development of a microfluidic platform is reported, i.e., the FBR-on-a-chip (FBROC) for modeling the cascade of events during immune cell response to implants. The platform models the native implant microenvironment where the implants are interfaced directly with surrounding tissues, as well as vasculature with circulating immune cells. The study demonstrates that the release of cytokines such as monocyte chemoattractant protein 1 (MCP-1) from the extracellular matrix (ECM)-like hydrogels in the bottom tissue chamber... 

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... 

Fabrication of well-ordered and bio-mimetic scaffolds is one of the most important research lines in tissue engineering. Different techniques have been utilized to achieve this goal, however, each method has its own disadvantages. Recently, melt electrowriting (MEW) as a technique for fabrication of well-organized scaffolds has attracted the researchers’ attention due to simultaneous use of principles of additive manufacturing and electrohydrodynamic phenomena. In previous research studies, polycaprolactone (PCL) has been mostly used in MEW process. PCL is a biocompatible polymer with characteristics that make it easy to fabricate well-arranged structures using MEW device. However, the... 

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... 

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... 

Efficient strategies to promote microvascularization in vascular tissue engineering, a central priority in regenerative medicine, are still scarce; nano- and micro-sized aggregates and spheres or beads harboring primitive microvascular beds are promising methods in vascular tissue engineering. Capillaries are the smallest type and in numerous blood vessels, which are distributed densely in cardiovascular system. To mimic this microvascular network, specific cell components and proangiogenic factors are required. Herein, advanced biofabrication methods in microvascular engineering, including extrusion-based and droplet-based bioprinting, Kenzan, and biogripper approaches, are deliberated with... 

Scaffolds for tissue engineering of specific sites such as cardiac, nerve, and bone tissues need a comprehensive design of three dimensional materials that covers all aspects of chemical composition and physical structures, required for regeneration of desired cells. Hydrogels, possessing highly hydrated and interconnected structures, are promising materials for tissue engineering applications. Improvement of an injectable hydrogel from biocompatible polysaccharides and poly‑N‑isopropyl acryl amide enriched with Au nanoparticles are the main goal of this study. Two main enhancements in this study are included mixture design of the components and addition of Au nanoparticles to access a... 

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... 

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... 

Conductive self -electrical stimuli bioactive scaffolds could be used the potential for peripheral nerve regeneration with the maximum efficiency. To produce such conductive self-electrical stimuli bioactive scaffolds, chopped spun piezoelectric nanofibers of polyvinylidene fluoride/mesoporous silica nanoparticle (PVDF/MCM41) are prepared and incorporated in gellan/polyaniline/graphene (gellan/PAG) nanocomposites which have been previously prepared by incorporation of polyaniline/graphene (PAG) nanoparticles in gellan gel at 80 °C. Highly conductive binary doped polyaniline/graphene nanoparticles are prepared by chemical oxidative polymerization of aniline monomer using in-suite... 

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... 

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... 

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... 

Small diameter vascular grafts (<6 mm) are highly demanded for patients suffering from severe occluded arteries to be used as a bypass or substituted conduit. Fabricating a graft with appropriate structural, mechanical and cell growth properties which has simultaneously anti-thrombogenic trait is a challenge nowadays. Here, we proposed a bilayer heparinized vascular graft that can mimic the structural and mechanical characteristics close to those of the native coronary artery by combining electrospinning and freeze drying methods. In this study, the inner layer was made by co-electrospinning of synthetic polymer, poly-caprolactone (PCL) and the natural polymer, gelatin (Gel). Also, heparin...